High-yield production of completely linear dextrans and isomalto-oligosaccharides by a truncated dextransucrase from Ligilactobacillus animalis TMW 1.971.

Several lactic acid bacteria are capable of producing water-soluble exopolysaccharides such as dextran from sucrose by using glucansucrases. Several recombinant glucansucrases were described, however, yields were often limited and most dextrans were branched at position O3. In this study, the dextransucrase from Ligilactobacillus animalis TMW 1.971 was recombinantly produced without its N-terminal variable region and used for dextran synthesis. The enzyme expressed well and showed very high total as well as transferase activities compared to other glucansucrases. It was able to transfer nearly all glucose from sucrose to oligo- and polymeric products under certain conditions (about 95 % of glucose transferred). The high efficiency of the enzyme made it possible to obtain absolute dextran yields of up to 214.9 g/L from a 1.5 M sucrose solution. Structural characterization of the products showed that the dextrans produced have a rather low molecular weight, a narrow size distribution, and are completely linear. Furthermore, we showed that various low molecular weight dextrans or 1,6-linked isomalto-oligosaccharides can be efficiently produced by acid hydrolysis. Overall, we demonstrated that Ligilactobacillus animalis TMW 1.971 dextransucrase can be used to efficiently synthesize dextrans with a quite unique structural composition. The dextrans produced have a high potential for further applications such as synthesis of copolymers or size standards with a very defined molecular structure.

Tough polyacrylic acid hydrogels with stable swelling and active functionalities enabled by quaternized cellulose nanofibrils and iron ions for absorbent pad interlayers.

Hydrogels are highly sought-after absorbent materials for absorbent pads; however, it is still challenging to achieve a satisfactory balance between mechanical performance, water absorption capacity, and active functionalities. In this work, we presented double-network hydrogels synthesized through acrylic acid (AA) polymerization in the presence of quaternized cellulose nanofibrils (QCNF) and Fe3+. Spectroscopic and microscopic analyses revealed that the combined QCNF and Fe3+ facilitated the formation of double-network hydrogels with combined chemical and physical crosslinking. The synergistic effect of QCNF and Fe3+ resulted in impressive mechanical properties, including tensile strength of 1.98 MPa, fracture elongation of 838.8 %, toughness of 7.47 MJ m-3, and elastic modulus of 0.35 MPa. In comparison to the single-network PAA hydrogel, the PAA/QCNF/Fe3+ (PQFe) hydrogels showed higher and relatively stable swelling ratios under varying pH levels and saline conditions. The PQFe hydrogels exhibited notable antioxidant activity, as evidenced by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and demonstrated effective antibacterial activity against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These hydrogels show promising potential as an absorbent interlayer in absorbent pads for active food packaging.

Morphological Changes in the Infrapatellar Fat Pad During Walking Detected by Dynamic Ultrasound in Healthy Volunteers.

Aim This study aimed to verify specific morphological changes in the infrapatellar fat pad (IFP) during walking in healthy young participants. Methods A total of 17 healthy young participants (mean age, 22.8 ± 0.9 years) were recruited in this cross-sectional study. The IFP was evaluated using ultrasonography in three conditions: supine, standing, and walking. The IFP value was described as the thickness of the distal section of the IFP. Additionally, in the walking condition, the IFP was captured in video mode on ultrasonography, and its dynamics were recorded. The waveform of the IFP was produced using the sequence of the IFP thickness on each image. The morphological change of IFP (ΔIFP) was calculated in the IFP waveform and was shown as the difference in IFP thickness between the maximum and minimum at the beginning of the early stance phase. Moreover, kinematics and kinetic data were evaluated using a three-dimensional motion system, and the knee flexion angle (KFA) and knee flexion moment (KFM) were obtained. Results The thickness of the IFP during walking was significantly greater than that during the supine and standing conditions (p < 0.001 for both). The IFP waveform during walking showed a gradual increase during the stance phase and a decrease during the swing phase of the gait cycle. ΔIFP was 1.35 ± 0.42 mm and significantly correlated with the KFM (r = 0.59, p = 0.007). Conclusions Dynamic ultrasonography revealed a specific morphological change in the IFP during walking, which correlated with the KFM.

Lateral flow immunoassay device to detect staphylococcal enterotoxin B (SEB) in durian candy.

Staphylococcal enterotoxin B (SEB), a potent enterotoxin produced by Staphylococcus aureus, has been implicated in incidences of Staphylococcal food poisoning in the Philippines. The use of lateral flow immunoassay devices to detect this toxin in solid food samples, like durian candy, at the point of sampling is constrained by the requirement for sample purification (e.g. centrifugation). This problem is also true with the other applications of LFIA devices on food samples. To overcome this challenge, a lateral flow immunoassay (LFIA) device capable of detecting SEB in unpurified durian candy sample was developed in this study. A modified LFIA device was assembled with three layers of glass fiber pads functioning as sample pads instead of a conventional cellulose fiber pad. Unlike with the cellulose fiber pad, the glass fiber sample pads acted as filter and allowed the flow of a 1:5 dilution of durian candy. The LFIA device applied to spiked 1:5 diluted durian candy samples achieved a visual limit of detection of 5 ng/mL for SEB, which is twofold lower than reported for previous LFIA devices designed to detect SEB in food samples.

Routine Ankle-Brachial Index (ABI) measurement: a window into atherosclerosis and early left ventricular dysfunction in patients diagnosed with cancer.

BACKGROUND: Cancer therapy is considered to cause accelerated ischemia. Ankle-Brachial Index (ABI) measurement is an inexpensive, simple, available test for the early diagnosis of peripheral artery disease (PAD); however, it is not performed routinely. We aimed to evaluate the role of routine ABI measurement for the diagnosis of PAD among patients diagnosed with cancer and whether it correlates with left ventricular (LV) dysfunction. METHODS: A retrospective, single-center study including patients diagnosed with cancer at Tel Aviv Sourasky Medical Center. The cohort included patients performing routine ABI and LV global longitudinal strain (GLS) echocardiography. The primary endpoint was the prevalence of PAD and whether it correlates with LV dysfunction, defined by LV GLS absolute value < 19%. The secondary composite endpoint evaluated the association between reduced ABI to LV dysfunction and all-cause mortality. RESULTS: Among 226 patients, PAD was diagnosed in 14 patients (6%). We revealed a positive correlation between ABI and LV GLS (r = 0.22, p < 0.01) with a reduced mean ABI score among patients with reduced LV GLS. A reduced mean ABI was observed among the positive composite endpoint group; however, it was not statistically significant (p = 0.35). CONCLUSIONS: We report, for the first time to our knowledge, the routine use of ABI testing among patients diagnosed with cancer. ABI showed a significant correlation to LV GLS, implying a potential tool in the early diagnosis of atherosclerosis and cardiotoxicity. Considering its low cost and availability, future prospective trials are needed to integrate its role in routine assessment.

Identification of Decedents by Restoring Mummified Fingerprints: Forensic Dermatology in the Investigation of Mummy Dermatoglyphics.

Fingerprints are created by elevations and depressions on the fingertip pads. Each person has their own unique fingerprints which can be used in the identification of that individual when alive, during the immediate postmortem period, or even after the digits have become mummified. Mummification can occur naturally; it can be partial (such as localized to only the hands and feet, extensive, or complete. Obtaining fingerprints after the skin has become mummified can be attempted while the digits remaining intact with the hand; however, the digits may need to be removed from the hand and the finger pads may also need to be separated from the underlying bone to secure an adequate fingerprint. Frequently, the mummified tissue needs to be rehydrated; numerous solutions have been used that increase the turgor of the digits, provide softening and pliability of the tissue, and enhance the details of the finger pad ridges. An aqueous solution of sodium carbonate (either combined with acetic acid or combined with 95 percent ethanol and distilled water) was found to be most effective for rehydration. Thereafter, various techniques can be attempted to obtain the fingerprint. These include the traditional method of inking and rolling of the finger or photographing the finger. Powders (such as aluminum powder, black fingerprint powder, white cornstarch-based powder, or fluorescent powder) can be used to enhance the ridge features; adhesive tape can be pressed against the powdered digit and the print pattern preserved by applying the adhesive tape to a clear transparency sheet. In addition, molds (using modeling clay or silicone rubber) and casts (using plaster of Paris, dental casting materials, or putty) can be made of the digits; either the molds or the casts or both can be photographed with or without prior application of fingerprint powder. Transillumination, using a fiber optic light source to illuminate the epidermis and underlying remaining dermis of a scraped and defleshed finger pad can be used to demonstrate the finger ridge pattern when the photographing the tip of the digit. In summary, forensic dermatology can have an integral role in obtaining fingerprints from mummified digits, which can be successfully used for the identification of the decedent.

The Role of Plain CT in Assessing and Estimating Normal Values of Pericardial Fat Pad Thickness and Their Correlation With Patient's Age, Gender, Body Weight, and Body Mass Index.

Introduction The pericardial fat pad, located anteriorly to the heart between the pericardium and myocardium, has garnered significant interest in cardiovascular research due to its potential role in the pathophysiology of various cardiac conditions. Despite its proximity to the myocardium, it is distinct from the epicardial fat depot found between the myocardium and the visceral layer of the pericardium. Studies have shown that excess pericardial fat is associated with an increased risk of heart failure and other cardiovascular diseases. Non-contrast computed tomography (CT) is a reliable, non-invasive method for assessing pericardial fat pad thickness, offering less radiation exposure compared to other imaging modalities. Establishing standardized measurements for pericardial fat pad thickness is essential, particularly for the South Indian population, which may exhibit unique genetic, dietary, and lifestyle influences on these measurements. Materials and methods A cross-sectional study was conducted on 300 participants from South India, stratified into three age groups: 18-35, 36-50, and 51-70 years, with body weights ranging from 45 kg to 120 kg. Participants were recruited from outpatient departments and community outreach programs, ensuring equal representation from each age group. Non-contrast CT imaging was performed using a Siemens Somatom goTop 128 Slice CT scanner to measure pericardial fat pad thickness and correlate it with age, gender, body weight, and body mass index. Exclusion criteria included diagnosed cardiac or pericardial diseases, prior chest surgery or trauma, pregnancy, and contraindications to CT scans. Ethical approval was obtained, and informed consent was collected from all participants. Data analysis was performed using SPSS software, employing descriptive statistics, ANOVA, t-tests, and Pearson's correlation. Results The study included 300 participants, with an equal gender distribution of 150 males and 150 females. Pericardial fat pad thickness increased with age, averaging 4.2 mm in the 18-35 age group, 5.1 mm in the 36-50 age group, and 6.4 mm in the 51-70 age group. Males exhibited a higher average thickness (5.6 mm) compared to females (5.0 mm). Body weight also showed a positive correlation with pericardial fat pad thickness, with mean values increasing from 4.5 mm in the 45-60 kg range to 6.7 mm in the 106-120 kg range. Statistical analysis confirmed significant differences in pericardial fat pad thickness across age groups, genders, and weight categories, emphasizing the importance of these factors in assessing cardiovascular risk. Conclusion This study provides a benchmark for pericardial fat pad thickness in the Kancheepuram Population of South India, highlighting its correlation with age, gender, body weight, and body mass index. The findings underscore the significance of non-invasive CT imaging in evaluating cardiovascular risk factors. Further research should focus on longitudinal studies and advanced imaging techniques to enhance the diagnostic accuracy and clinical relevance of pericardial fat pad measurements. The established reference values can aid clinicians in identifying individuals at higher risk for cardiovascular diseases, facilitating early intervention and management.

Redundant role of PAD2 and PAD4 in the development of cardiovascular lesions in a mouse model of Kawasaki Disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. While circulating neutrophils are increased and activated during acute KD, it is unclear whether neutrophils and neutrophil extracellular traps (NETs) contribute to the pathogenesis of KD. Peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination and essential for NETs formation, is implicated in the pathogenesis of various diseases. Here, we used the Lactobacillus casei cell wall extract (LCWE)-induced mouse model of KD vasculitis to determine the contribution of PAD4 in KD vasculitis. We found that the pan-PADs inhibitor, Cl-amidine, significantly reduced LCWE-induced cardiovascular lesions, but neutrophil-specific Padi4 KO mice did not impact development of KD vasculitis. While in vitro treatment of macrophages, which highly express Padi4, with Cl-amidine inhibited IL-1ßsecretion, macrophage-specific Padi4 KO mice did not reduce the lesions. Padi4-/- mice also developed KD vasculitis, AFM30a, a PAD2 inhibitor, significantly reduced KD vasculitis in Padi4-/- mice, indicating a compensatory role of PAD2 in PAD4 deficiency. We also identified several citrullinated proteins in macrophages with constitutively active NLRP3 inflammasome that were inhibited by Cl-amidine treatment, suggesting that protein citrullination participates in NLRP3 inflammasome activation. These data indicate a dispensable role for PAD4-dependent NETs formation, and a redundant role of PAD2 and PAD4 in this murine KD vasculitis. The cardioprotective effects of Cl-amidine to reduce the severity of murine KD vasculitis is not limited to PAD4 inhibition and may include decreased citrullination in the inflammasome pathway.

3D segmentation and quantitative analysis of age-related changes in the Hoffa fat pad using MRI.

The infrapatellar fat pad (IFP), also known as the Hoffa fat pad, is an essential structure in the knee joint with diverse functions and characteristics. Pathological changes in it can lead to anterior knee pain and impingement. The aim of this study was to investigate the relationship between age and Hoffa fat pad volume. A retrospective analysis was conducted on MRI scans of 100 individuals aged 10-80 years with no Hoffa fat pad pathology. The IFP was meticulously segmented on each sagittal and coronal MRI plane and its volume was calculated on the basis of the segmented boundaries. Correlation analysis was used to explore the relationships among age, sex, height, weight, and patella-related variables. Contrary to the hypothesis, there was no significant correlation between age and Hoffa fat pad volume. However, there were strong positive correlations between Hoffa fat pad volume and individuals' height, patellar height, and patellar ligament length. Multivariable linear regression analysis revealed that height, weight, patellar height, and patellar ligament length collectively explained 67% of Hoffa fat pad volume variability. These findings suggest that the Hoffa fat pad adapts to accommodate morphological changes in the knee joint as individuals grow taller. In conclusion, our study examined Hoffa fat pad volume in individuals across the age spectrum, using advanced imaging techniques to reveal the importance of considering height and knee-related variables for assessing Hoffa fat pad volume. This elucidates age-related volume changes and highlights the need for further research to understand its functional implications and interactions within the knee joint, with the aim of improving orthopedic interventions.

Revamped Role for Approved Drug: Integrative Computational and Biophysical Analysis of Saquinavir's PAD4 Inhibition for Rheumatoid Arthritis.

The pursuit of novel therapeutics is a complex and resource-intensive endeavour marked by significant challenges, including high costs and low success rates. In response, drug repositioning strategies leverage existing FDA-approved compounds to predict their efficacy across diverse diseases. Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in protein citrullination, a process implicated in the autoimmune pathogenesis of rheumatoid arthritis (RA). Targeting PAD4 has thus emerged as a promising therapeutic approach. This study employs computational and enzyme inhibition strategies to identify potential PAD4-targeting compounds from a library of FDA-approved drugs. In-silico docking analyses validated the binding interactions and orientations of screened compounds within PAD4's active site, with key residues such as ASP350, HIS471, ASP473, and CYS645 participating in crucial hydrogen bonding and van der Waals interactions. Molecular dynamics simulations further assessed the stability of top compounds exhibiting high binding affinities. Among these compounds, Saquinavir (SQV) emerged as a potent PAD4 inhibitor, demonstrating competitive inhibition with a low IC50 value of 1.21 ± 0.04 µM. In-vitro assays, including enzyme kinetics and biophysical analyses, highlighted significant changes in PAD4 conformation upon SQV binding, as confirmed by circular dichroism spectroscopy. SQV induced localized alterations in PAD4 structure, effectively occupying the catalytic pocket and inhibiting enzymatic activity. These findings underscore SQV's potential as a therapeutic candidate for RA through PAD4 inhibition. Further validation through in-vitro and in-vivo studies is essential to confirm SQV's therapeutic benefits in autoimmune diseases associated with dysregulated citrullination.

Drones reduce the time to defibrillation in a highly visited non-urban area: A randomized simulation-based trial.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) has a high global incidence and mortality rate, with early defibrillation significantly improving survival. Our aim was to assess the feasibility of autonomous drone delivery of automated external defibrillators (AED) in a non-urban area with physical barriers and compare the time to defibrillate (TTD) with bystander retrieval from a public access defibrillator (PAD) point and helicopter emergency medical services (HEMS) physician performed defibrillation. METHODS: This randomized simulation-based trial with a cross-over design included bystanders performing AED retrievals either delivered by automated drone flight or on foot from a PAD point, and simulated HEMS interventions. The primary outcome was the time to defibrillation, with secondary outcomes comparing workload, perceived physical effort, and ease of use. RESULTS: Thirty-six simulations were performed. Drone-delivered AED intervention had a significantly shorter TTD [2.2 (95 % CI 2.0-2.3) min] compared to PAD retrieval [12.4 (95 % CI 10.4-14.4) min] and HEMS [18.2 (95 % CI 17.1-19.2) min]. The self-reported physical effort on a visual analogue scale for drone-delivered AED was significantly lower versus PAD [2.5 (1 - 22) mm vs. 81 (65-99) mm, p = 0.02]. The overall mean workload measured by NASA-TLX was also significantly lower for drone delivery compared to PAD [4.3 (1.2-11.7) vs. 11.9 (5.5-14.5), p = 0.018]. CONCLUSION: The use of drones for automated AED delivery in a non-urban area with physical barriers is feasible and leads to a shorter time to defibrillation. Drone-delivered AEDs also involve a lower workload and perceived physical effort than AED retrieval on foot.

The biphasic role of the infrapatellar fat pad in osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. It is a whole organ disease characterized by cartilage degeneration and varying degrees of synovitis, involving pathological changes in all joint tissues, such as cartilage, subchondral bone, ligaments, meniscus, synovium, and infrapatellar fat pad (IPFP). IPFP is the largest adipose tissue structure in the knee joint and is composed of fat cells, immune cells and blood vessels. Moreover, IPFP is located close to the cartilage and bone surface so that it may reduce the impact of loading and absorb forces generated through the knee joint, and may have a protective role in joint health. IPFP has been shown to release various cytokines and adipokines that play pro-inflammatory and pro-catabolic roles in cartilage, promoting OA progression. Intra-articular injections of IPFP-derived mesenchymal stem cells and exosomes have been shown to reduce pain and prevent OA progression in patients with knee OA. Previous studies have shown that IPFP has a biphasic effect on OA progression. This article reviews the latest research progress of IPFP, discusses the role and mechanism of IPFP in OA, provide new intervention strategies for the treatment of OA. This article will also discuss the handling of IPFP during the procedure of total knee arthroplasty.

Comparison of lecture-based learning with presentation-assimilation-discussion method in occupational bloodborne exposure education of nursing students, a randomised trial.

BACKGROUND: Occupational Bloodborne Exposures (OBEs) are incidents where healthcare workers come into contact with blood or other potentially infectious materials, leading to risks of transmitting bloodborne pathogens. Nursing students, often in direct contact with patients, face heightened risks due to their duties. METHODS: First, we conducted a cross-sectional survey using a OBEs questionnaire to explore the knowledge, attitudes, practices, and needs regarding OBEs among nursing students. Subsequently, we used a randomized controlled trial (RCT) to compare the impact of the Presentation-Assimilation-Discussion (PAD) method with the traditional lecture-based learning (LBL) method on OBEs education for nursing students. Pre-test, post-test, and retention test were used to observe the teaching effectiveness, and the students' feedback on the teaching method was also observed. RESULTS: In the cross-sectional survey, we found that nursing students lacked sufficient knowledge and management skills regarding OBEs but recognized the importance of standard precautions and expressed a desire for systematic OBEs training during their education and internships. In the RCT, the total, theoretical, and practical scores of the PAD and LBL groups were comparable in the pre-test (56.70 ± 3.47 vs. 56.40 ± 3.95, 33.09 ± 3.39 vs. 33.33 ± 2.44, 23.61 ± 4.66 vs. 23.07 ± 4.84, p > 0.05). After training, the PAD model demonstrated an advantage over the LBL model in immediate total (84.25 ± 4.06 vs. 78.95 ± 4.23, p < 0.001), theoretical (54.32 ± 2.43 vs. 51.44 ± 2.58, p < 0.001), and practical scores (29.93 ± 3.90 vs. 27.51 ± 4.33, p < 0.01). It also showed superior retention of total (69.05 ± 3.87 vs. 65.77 ± 2.94, p < 0.001) and theoretical scores (39.05 ± 3.05 vs. 36.23 ± 3.18, p < 0.001). However, there was no significant difference in the retention of practical scores between the two groups (30.00 ± 4.76 vs. 29.53 ± 3.73, p > 0.05). The PAD group benefited more across various learning dimensions but reported a higher study load. CONCLUSIONS: Our study reveals that the PAD model could be a valuable approach for teaching OBEs to nursing students.

Association of health status and hospitalization risk for peripheral artery disease in the PORTRAIT registry.

BACKGROUND: Healthcare utilization for patients with peripheral artery disease (PAD) is high, but stratifying patients' risk of hospitalization at initial evaluation is challenging. We examined the association between health status at PAD presentation and risk of (1) combined all-cause hospital admissions and emergency department (ED) visits and (2) all-cause hospital admissions. METHODS: Patients with claudication enrolled at US sites in the PORTRAIT registry were included. Health status was assessed using the Peripheral Artery Questionnaire (PAQ), a PAD-specific patient-reported outcome measure. Crude overall and cause-specific hospital admissions and ED visits were reported by PAQ overall summary score (PAQ-OS) ranges (0-24, 25-49, 50-74, and 75-100). Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards models examined the association between baseline PAQ scores and (1) combined all-cause hospital admissions or ED visits and (2) all-cause hospital admissions over 12 months. RESULTS: Of 796 patients, 349 (44%) had a hospital admission or ED visit over 12 months. Patients in the lowest (PAQ-OS = 0-24) versus the highest range (PAQ-OS = 75-100) had higher rates of 12-month (53.3% vs 22.4%) hospital admission and ED visits. In the adjusted model, each 10-point decrease in PAQ-OS was associated with a higher risk of all-cause hospital admission and ED visits (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) and all-cause hospital admission (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) at 12 months. CONCLUSION: PAD-specific health status is associated with an increased risk of healthcare utilization. Baseline health status may help stratify risk in patients with PAD, although replication and further validation of results are necessary.

Microbial and Quality Attributes of Beef Steaks under High-CO2 Packaging: Emitter Pads versus Gas Flushing.

Over 21 days of cold storage, the quality and microbial composition of beef steaks in response to different high-CO2 packaging conditions achieved by flushing gas mixtures or embedding gas emitters into the packages were studied. The results revealed that the high levels of CO2, achieved by either the gas flushing or the CO2 emitter pads, effectively controlled the number of aerobic counts. The headspace CO2 increased quickly in response to using the CO2 emitter pads, and the meat samples presented different pH levels and surface color (a* and b*) values compared to the samples packaged with the gas flushing technique. Excessive accumulation of gas in the packages that contained CO2 emitters resulted in package swelling and higher levels of drip loss. The longest overall quality and attractive red color of the meat samples were observed when the packages were initially flushed with the headspace gas mixture containing high levels of oxygen. Overall, using CO2 emitters for meat packaging can be suggested when a topfilm with proper permeability to O2 and CO2 gases is used to regulate the internal CO2/O2 and gas/product ratios.

Percutaneous Cannulation of the Axillary Artery: Does the Position of the Brachial Plexus Correlate With Bony Landmarks That Could Be Used to Reduce the Risk of Complications?

Introduction Endovascular surgery is an innovative way of carrying out procedures such as transcatheter aortic valve insertion where the femoral artery is commonly used as an access point. Conditions like peripheral arterial disease can make endovascular procedures challenging when atherosclerotic plaques compromise the integrity of lower limb vessels. An alternative access point for these patients is required. Access through the axillary artery has been proposed; however, the close proximity of the brachial plexus introduces a risk of neural complications. This study aims to find an anatomical or bony landmark(s) to help identify an area of safety on the axillary artery that can be used to gain access. Materials and methods Nine cadavers were used in the study and five parameters were measured using the acromion and coracoid processes as bony landmarks. The 1st parameter measured the distance between the acromion and the coracoid process. The 2nd parameter was the diameter of the axillary artery taken at a plane extending from the acromion to the coracoid process - now defined as the coracoacromial plane. The 3rd measurement was the distance between the coracoid process and the midpoint of the axillary artery diameter taken at the above plane; it is proposed this will form a safe point on the axillary artery. The 4th parameter measured was the distance between the safe point on the axillary artery and the median nerve. The 5th parameter was the distance between the safe point and the thoracoacromial trunk. Measurements were taken using digital callipers and were recorded for both sides of the cadaver except for one. Using the data from the measurements, an area of safety was calculated and statistical analysis was carried out using Student's t-test and Pearson's correlation to look for significant differences between the left and right sides. Results The mean distance from the safe point of the axillary artery to the median nerve was 23.25 mm on the left and 27.10 mm on the right. The p-value was 0.7, which indicated no significant differences between both sides. The mean distance between the safe point and the thoracoacromial trunk was 11.31 mm on the left and 13.21 mm on the right. The p-value was 0.24, indicating no significant differences between both sides. The mean area of safety was larger on the right side with an area of 184.37 mm and smaller on the left side with an area of 158.93 mm. The p-value was 0.62, which indicated no significant differences between both sides. There was no clear relationship between the distance from the acromion to the coracoid process compared to the distance between the acromion and a defined safe point on the axillary artery. This was confirmed using a Pearson's correlation test, which resulted in a p-value of 0.53 on the left and 0.93 on the right. These values were above the critical value, suggesting no correlation. Conclusion The acromion and the coracoid process are important bony landmarks that can be used to define the coracoacromial plane that traverses the axillary artery whereby avoiding the cords of the brachial plexus, the median nerve as well as the thoracoacromial trunk. Implementing this approach to define a safe vascular access point on the axillary artery could minimise complications like brachial plexus injuries. Further studies on a larger sample size using radiological methods may need to be carried out to help increase confidence in these preliminary cadaveric findings.

Spinal Cord Stimulation for Intractable Chronic Limb Ischemia: A Narrative Review.

Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease, significantly impacting quality of life, morbidity and mortality. Common complications include severe limb pain, walking difficulties, ulcerations and limb amputations. For cases of CLI where surgical or endovascular reconstruction is not possible or fails, spinal cord stimulation (SCS) may be a treatment option. Currently, SCS is primarily prescribed as a symptomatic treatment for painful symptoms. It is used to treat intractable pain arising from various disorders, such as neuropathic pain secondary to persistent spinal pain syndrome (PSPS) and painful diabetic neuropathy. Data regarding the effect of SCS in treating CLI are varied, with the mechanism of action of vasodilatation in the peripheral microcirculatory system not yet fully understood. This review focuses on the surgical technique, new modalities of SCS, the mechanisms of action of SCS in vascular diseases and the parameters for selecting CLI patients, along with the clinical outcomes and complications. SCS is a safe and effective surgical option in selected patients with CLI, where surgical or endovascular revascularization is not feasible.

The Influence of Dapagliflozin on Foot Microcirculation in Patients with Type 2 Diabetes with and without Peripheral Arterial Disease-A Pilot Study.

The results of large cardiovascular studies indicate that SGLT-2 inhibitors may increase the risk of leg amputations. This study aims to investigate whether dapagliflozin therapy affects peripheral vascular oxygenation, i.e., microcirculation in the foot, as measured by transcutaneous oxygen pressure (TcPO2) in patients with type 2 diabetes (T2DM) and peripheral arterial disease (PAD) compared to patients without PAD. The patients with PAD were randomized into two groups. In the first 35 patients with PAD, dapagliflozin was added to the therapy; in the other 26 patients with PAD, other antidiabetic drugs were added to the therapy. Dapagliflozin was added to the therapy in all patients without PAD. TcPO2 measurement, Ankle Brachial Index (ABI), anthropometric measurements, and laboratory tests were performed. After a follow-up period of 119.35 days, there was no statistically significant difference in the reduction of mean TcPO2 values between the group with T2DM with PAD treated with dapagliflozin and the group with T2DM with PAD treated with other antidiabetic drugs (3.88 mm Hg, SD = 15.13 vs. 1.48 mm Hg, SD = 11.55, p = 0.106). Patients with control TcPO2 findings suggestive of hypoxia (TcPO2 < 40 mm Hg) who were treated with dapagliflozin had a clinically significant decrease in mean TcPO2 of 10 mm Hg or more (15.8 mm Hg and 12.90 mm Hg). However, the aforementioned decrease in TcPO2 was not statistically significantly different from the decrease in TcPO2 in the group with PAD treated with other diabetic medications (p = 0.226, p = 0.094). Based on the available data, dapagliflozin appears to affect tissue oxygenation in T2DM with PAD. However, studies with a larger number of patients and a longer follow-up period are needed to determine the extent and significance of this effect.

Harnessing marine natural products to inhibit PAD4 triple mutant: A structure-based virtual screening approach for rheumatoid arthritis therapy.

Peptidylarginine deiminase type4 (PAD4) is a pivotal pro-inflammatory protein within the human immune system, intricately involved in both inflammatory processes and immune responses. Its role extends to the generation of diverse immune cell types, including T cells, B cells, natural killer cells, and dendritic cells. PAD4 has recently garnered attention due to its association with a spectrum of inflammatory and autoimmune disorders, notably rheumatoid arthritis (RA). Mutations in the PAD4 gene, leading to the conversion of arginine to citrulline, have emerged as significant factors in the pathogenesis of RA and related conditions. As a calcium-dependent enzyme, PAD4 is central to the citrullination process, a crucial post-translational modification implicated in disease pathophysiology. Its critical role in autoimmune disorders and inflammation makes PAD4 a prime candidate for therapeutic intervention in RA. Inhibiting PAD4 presents a promising avenue for mitigating inflammatory responses and curtailing joint degradation and impairment. To explore its therapeutic potential, a structure-based virtual screening (SBVS) approach was employed, harnessing an array of marine natural products (MNPs) sourced from databases such as CMNPD, MNPD, and Seaweed. Notably, MNPD10752, CMNPD12680, and CMNPD2751 emerged as potential hit molecules, exhibiting adherence to essential pharmacokinetic properties and favorable toxicity profiles. Quantum mechanics studies using density functional theory (DFT) calculations revealed the inhibitory potential of these identified natural products. Further structural elucidation through molecular dynamics simulations (MDS) and principal component-based free energy landscape (FEL) analysis shed light on the stability of MNP-bound PAD4 complexes. In conclusion, this computational study serves as a stepping stone for further experimental evaluation, aiming to explore the potential of MNPs in addressing PAD4-related human pathologies.

Adverse Health Outcomes 3 Years after Radical Prostatectomy Compared with Men in the General Population: A Study from the Cancer Registry of Norway.

INTRODUCTION: Studies about adverse health outcomes (AHOs) after radical prostatectomy (RP) in population-based contemporary prostate cancer (PCa) patients are limited, as well as knowledge about corresponding data from age-similar men from the general population (Norms). We compared selected AHOs (pad use, intercourse inability), related problems (bother) and quality of life (QoL) between PCa patients and Norms. PATIENTS AND METHODS: The Cancer Registry of Norway (CRN) provided data on PCa patients diagnosed in 2017-2019 and treated with RP who completed the EPIC-26 and EORTC-QLQ-C30 questionnaires 24-48 months after surgery (n = 1501). The CRN also established a group of Norms (n = 1894). Dichotomized EPIC-26 outcomes: daily use of ≥1 pad (Item#3), quality of erections (Item#9) and related bother (Item#4a/#12). EORTC-QLQ-C30: quality of life (Item#30). Multivariable logistic regressions explored associations between selected covariates and outcomes. RESULTS: In total, 41% of the patients and 5% in Norms reported pad use, the comparable figures for intercourse inability being 84% (Patients) and 48% (Norms). Among pad users, 24% of the patients and 25% of the Norms described bother. 52% of patients and 35% Norms with intercourse inability. Only bilateral nerve-sparing surgery (NSS) significantly reduced the risk of pad use and intercourse inability. Compared to Norms, PCa patients were associated with pad use, intercourse inability, related bother, and good/ fair QoL. CONCLUSION: In these population-based cohorts, 2 in 5 patients used pads 3 years after RP, compared to 1 in 20 Norms. Intercourse inability was reported by 4 of 5 patients compared to 1 of 2 Norms. PCa patients were associated with good/ fair QoL. Bilateral NSS significantly reduced the risk of AHOs, highlighting the importance of this approach. Function and bother are different dimensions of urinary and sexual AHOs and must be reported separately. The findings from this study should be considered when counselling patients before RP.