Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics

The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium

A coarse-grained multiscale model to simulate morphological changes of food-plant tissues undergoing drying

Numerical modelling has emerged as a powerful and effective tool to study various dynamic behaviours of biological matter. Such numerical modelling tools have contributed to the optimisations of food drying parameters leading to higher quality end-products in the field of food engineering. In this context, on of the most recent developments is the mesh-free based numerical models, which have demonstrated enhanced capabilities to model cellular deformations during drying, providing many benefits compared to conventional grid-based modelling approaches. However, the potential extension of this method for simulating bulk level tissues has been a challenge due to the increased requirement for higher computaional time and resources. As a solution for this, by incorporating meshfree features, a novel coarse-grained multiscale numerical model is proposed in this work to predict bulk level (macroscale) deformations of food plant tissues during drying

A multiscale coarse grained model for simulating mechanical responses of plant food tissues

Plant food materials are highly sensitive to the external mechanical responses. Simulation of the material behaviour under mechanical loading is important in many engineering applications. Several researchers have used tissue based (macroscale) and cellular based (microscale) numerical models to assess the plant material behaviour. In doing so, generally, finite element modelling and meshfree based discretization strategies are commonly used and the latter has been proven to be more flexible, accurate and more robust in numerical simulations. This study aims to develop a coarse grained (CG) model for a cellular system of plant food tissue in microscale. The basic idea here is to maintain the accuracy given by the cellular scale while minimizing the computational cost for the simulations. The developed model accounts for the deformation of a coarse grained system under an external mechanical load. In order to represent the viscoelastic behaviour of a plant food material, we use a spring damper system connected to coarse grained beads. The model predictions show a satisfactory agreement with the morphological changes given by the cellular model. This developed CG model has laid a solid foundation for the further development of the multiscale model for the plant tissue

Trunk Injection Method for Introducing Chemical Formulations in to Rubber Trees

Natural Rubber is an important commodity to the economy of Sri Lanka. This industry makesexport earnings, sustain the livelihood of over thousands of people, supplement thousands ofhectares to the forest cover and provide many other socio-economic and ecological benefits.The economically important diseases are regarded as a major constraint for achievingpotential productivity levels of rubber cultivations. Hence management of these diseasesprovides economic benefits to rubber growers. The most popular method of disease control ischemical control. There are various chemical application techniques and spray applications,soil drenching, dusting or broadcasting are popular methods. Based on the age, type of thedisease or the prevailing weather conditions, the application technology needs to be changed.These conventional technologies have many health and environmental drawbacks. Therefore,economical and environmental friendly chemical application techniques have becomeimportant. The present study was aimed at investigating the trunk injection method forintroducing chemical formulations into trees. Several types of potential injectors are availableand the chemjet injectors described by Guest et al., (1994) was used throughout theexperiments. These injectors [Chemjet Trading (Pvt) Ltd, Australia] contain 20ml of thesolution and have a working pressure of 1 – 1.5 bars facilitating the formulation into the treesthrough drilled holes. The injection process was tested at Dartonfield Estate, on the Heveabrasiliensis clone RRIC 121. The average girth at the tested plants was 89 cm. Two analysesviz. 45, 60 to a depth of 4 cm from the outer bark was done. The uptake rates weredetermined using 8% tebuconazole in aqueous solutions. Uptake of the fungicide was slightlyhigher in deep injected method compared to shallow injection. The two angles tested againstthe liquid uptake too were not significantly different from each other. No interaction wasobserved among the injection angle and the depth of injection on the liquid uptake. More than70% of the trees had uptaken the entire 20ml injected volume within 48 hrs of injection.Trunk diameter had no effect on the uptaking process. The results obtained proved thepossibility of injecting liquids / chemical solutions into rubber trees. Trunk injection requireslow volumes of chemicals resulting in reduced cost in chemical applications. Minimumwastage of chemicals could be achieved together with reducing the impact of hazardouschemicals on the environment. Compared to the currently practiced chemical applicationmethods into trees, this application technique has many advantages

Affinity enrichment of extracellular vesicles from plasma reveals mRNA changes associated with acute ischemic stroke

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells’ mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV’s mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 109 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h

Expectations versus reality in chronic venous ulceration; a quality of life assessment study

Introduction: Chronic venous ulceration is a common problem worldwide with a significant effect onQuality of Life (QoL).Objectives: Our objective was to assess Sri Lankan patients’ perspective with regard to this scenario.Methods: We involved 141 consenting patients presenting to the OPD, National Hospital with a venousulcer lasting one month or more. Data was collected using an interviewer administered questionnaire, aclinical interview and a lower limb duplex scan. Short form 36 questionnaire was used for QoLassessment.Results: The majority were elderly (median age 53 years) men (n=9[69.5%]). Fifty four (38.3%) wereunemployed at the time of the study and 28 (19.9%) directly attributed the ulcer as the cause forunemployment. Median duration of ulcer was 10[1-360] months and mean Venous Clinical SeverityScore (VCSS) was 13.85(4-24). Family history (44[31.2%]), previous limb trauma or non-venoussurgery (24[17.0%]), smoking among men (57 [58.2%]) and history of pregnancy among females(34[79.1%]) were identified as risk factors. Role limitation due to physical health (28.4[SD 42.8]) androle emotional problems (40.9 [SD 46.7]) had a mean SF 36 score below 50. Factors such as pain,duration of ulcer, older age and higher BMI significantly affected many domains of QoL (p<0.05). Sixtysix (46.8%) patients continue to have ulcers despite having had surgical treatment for varicose veins.Conclusions: Venous ulcers have a considerable impact on the quality of life in Sri Lankan patientswith venous ulcer. The need for providing preventive and rapid healing methods together with socialsupport must be emphasized

Utility of WIfI foot assessment tool in a Sri Lankan setting; an initial experience

Introduction: Potential for limb salvage and wound healing in a lower limb ulcer depends on degreeof ischemia, wound grade and superadded foot infection.Objectives: Our objective was to assess the feasibility of applying WIfI classification system to stratifypatients presenting with limb ulceration according to risk of undergoing amputation and benefit ofrevascularization.Methods: Fifty four consecutive patients with ulcerated limbs presenting over two months to theUniversity unit at the National Hospital were staged according to the Society for Vascular Surgery(SVS)Wound, Ischemia, and Foot Infection (WIfI) classification system.Results: The median age was 64 (39-93), and 42 (79%) patients were males. Diabetes (87%),hypertension (53%), ischemic heart disease (14%), cerebrovascular disease (13%), chronic renal disease(13%) were identified risk factors. Smoking was reported among 35%. Median Anterior TibialArtery(ATA), Posterior Tibial Artery(PTA), Toe pressures, Ankle Brachial Index, Pole test values ofthe affected side lower limbs were 114.5mmHg, 107.5mmHg, 41mmHg, 0.87 and 85cm respectively.Values for the contralateral limb were 140mmHg, 120mmHg, 74mmHg, 1.0 and 85cm respectively.84% of ATA and 90 % of PTA pulses were not palpable on the affected side. Grades of ischemia were;none (23.3%), mild (27.9%), moderate (18.6%), severe (30.2%), grades of infection were none (20.9%),mild (37.2%), moderate (39.5%), severe (2.3%), and wound grades were 0(0%), 1(20%.9), 2(39.5%),3(39.5%). Estimated risk of amputation were high (65.1%), moderate (11.6%), low (11.6%), very low(11.6%) and estimated benefit of revascularization were high (46.5%) moderate (23.3%), low (7.0%),very low (23.3%).Conclusions: Application of WIfI system was useful to prioritize patients with eminent limb loss forurgent intervention. Toe pressure assessment for diabetic foot ulcer stratification should become acommon practice

Recent Innovations & Daily Problems. A new prosthesis in inguinal hernia repair:preliminary results of a pilot study.

Introduction: Elective surgery for inguinal hernia is affected by very low mortality « 1 per 10000 operation); in contrast, when surgery is carried out for complicated inguinal hernia, risks of postoperative complication are higher. TAPP is a world-wide accepted surgical practice in the treatment of elective bilateral or recurrent inguinal hernia, above all in young patients. Few exploratory studies were published on laparoscopic approach in the treatment of urgent complicated inguinal hernia. Aim of this study was to analyze feasibility (operative time, conversion rate), safety (postoperative morbidity, length of hospital stay) and quality of life (acute and chronic pain, return to work) of trans-abdominal pre-peritoneal laparoscopic hernia repair in acute incarcerated inguinal hernia. Rationale of laparoscopic trans-abdominal approach is the easier hernia reduction under vision and a better exploration of the abdominal cavity. Methods: from September 2012 to September 2013, 15 consecutive patients admitted in emergency at the Division of General Surgery of University "Sapienza", Polo Pontino, for acute incarcerated inguinal hernia were submitted to TAPP using 3 trocars (1 of 10 mm and 2 of 5mm) and polyester prosthesis fixed by fibrin glue. Exclusion criteria for laparoscopic approach were age III, previous abdominal surgery, signs of strangulated hernia. All of them were evaluated for operative time, conversion rate, postoperative morbidity, organ resection or other surgery required. All patients were scored for pain by Visual Analogic Scale (VAS) during postoperative in hospital stay at 7 days, 1,6 and 12 months after surgery. Results: median follow-up was 16 months and 12 as minimum. In all cases reduction of hernia was always possible and none conversion to open surgery was recorded, median operative time was 89 minutes (55-137 as range), omental resection was carried out in one patient (6,6%), no other organ resections needed, whereas contralateral hernia was diagnosed and repaired at the same time in 4 patients (26,6%). No major complications were observed, median blood loss was 100 ml, minor morbidity was contained to 18% represented by fever and wound infection of surgical umbilical scar. Median in hospital stay was 1,5 days with 1-5 days as range. Postoperative median acute pain, measured by visual analogic scale (VAS), was 2 (range:0-4), none patient referred any pain during follow-up. Median time of return to work was 6,5 days, ranged between 3 to 15 days. Patients' compliance to treatment and to follow-up was complete as well their satisfaction. Conclusions: In centres skilled for laparoscopy in emergency, TAPP could be considered a feasible and safe technique. In well-selected patients (especially if emolled in controlled clinical trial) TAPP could represent an alternative surgical approach for complicated incarcerated inguinal hernia to conventional open surgery even in urgency. The main advantages of laparoscopic approach are the ability to perform surgical hernia reduction under vision, a better exploration and evaluation of abdominal cavity and diagnosis and treatment of eventual contralateral defect of wall, otherwise often missed. Finally, the good control of acute and chronic pain, faster return to normal activity and work, better aesthetic results contributed to total satisfaction and compliance of the patients

Palaeogenomic analysis of black rat (Rattus rattus) reveals multiple European introductions associated with human economic history

The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we first generate a de novo genome assembly of the black rat. We then sequence 67 ancient and three modern black rat mitogenomes, and 36 ancient and three modern nuclear genomes from archaeological sites spanning the 1st-17th centuries CE in Europe and North Africa. Analyses of our newly reported sequences, together with published mitochondrial DNA sequences, confirm that black rats were introduced into the Mediterranean and Europe from Southwest Asia. Genomic analyses of the ancient rats reveal a population turnover in temperate Europe between the 6th and 10th centuries CE, coincident with an archaeologically attested decline in the black rat population. The near disappearance and re-emergence of black rats in Europe may have been the result of the breakdown of the Roman Empire, the First Plague Pandemic, and/or post-Roman climatic cooling.Peer reviewe

Perspectives on tracking data reuse across biodata resources

c The Author(s) 2024. Published by Oxford University Press.Motivation: Data reuse is a common and vital practice in molecular biology and enables the knowledge gathered over recent decades to drive discovery and innovation in the life sciences. Much of this knowledge has been collated into molecular biology databases, such as UniProtKB, and these resources derive enormous value from sharing data among themselves. However, quantifying and documenting this kind of data reuse remains a challenge. Results: The article reports on a one-day virtual workshop hosted by the UniProt Consortium in March 2023, attended by representatives from biodata resources, experts in data management, and NIH program managers. Workshop discussions focused on strategies for tracking data reuse, best practices for reusing data, and the challenges associated with data reuse and tracking. Surveys and discussions showed that data reuse is widespread, but critical information for reproducibility is sometimes lacking. Challenges include costs of tracking data reuse, tensions between tracking data and open sharing, restrictive licenses, and difficulties in tracking commercial data use. Recommendations that emerged from the discussion include: development of standardized formats for documenting data reuse, education about the obstacles posed by restrictive licenses, and continued recognition by funding agencies that data management is a critical activity that requires dedicated resources