Implementation of Critical Threshold Concept in Clinical Transplantation: A New Horizon in Distance Learning

Background: While variations in medical practice are a norm and each patient poses a multitude of challenges, many clinicians are not comfortable in dealing with unexpected complex issues even though they may have enough knowledge as demonstrated by passing a number of tricky certifying (or exit) examinations. One reason for the lack of self-efficacy, even if being endowed with good knowledge, is that we are not good in learning from errors. A regular reflective practice offers superb learning opportunities when a clinician is “stuck in a mire”. Difficult clinical situations warrant a flexible and, at the same time, an evidence-based approach to ensure that crucial decision-making process is correct and efficient. Each clinical case offers a great opportunity to reinforce these “threshold concepts”, however, not everyone of us is “blessed” with these crucial not-so-difficult-to-acquire skills so necessary to be a life-long learner. The faculty of this course (a totally on-line MSc in Transplant Sciences) aims for unceasing engagement with students in order to facilitate them to negotiate through “stuck places” and “tricky bends” in their own work place. This course, not just meant for knowledge transfer, provides a platform that allows participants (the students and faculty) to learn from each other’s experience by using “e-blackboard”. The mainstay of this course are twofold: (a) Emphasis on achieving critical decision-making skills, (b) Regular feedback to allow reflective practice and, thereby, constantly learning from errors and reinforcing good practices. The aim of this article is to assess the performance of educators and how well the “ethos of critical threshold” has been accepted from the perspective of students. Methods: The critical thresholds of each chapter in 4 modules of this totally on-line course were defined to a razor-sharp precision. Learning objectives of learning activity were defined to achieve constructive alignment with critical threshold. We employed level 1, 2, 4 and 5 of Kirkpatrick pyramid, (a) for the evaluation of performance of educators of program, and (b) to evaluate the acceptance of this non-traditional format in clinical medicine education by postgraduate 80 students in 22 countries.Results: Students’ survey (Kirkpatrick level 1) was done only for module 1 of cohort 1 reported students’ satisfaction rate of 93%. Excluding a total of 12 drop-outs in 2 modules (n=10 in first cohort’s module 1, and n=2 in module 2), as many as 93% of students of first cohort passed module. Nine out of 60 registrants of module 1 in 2nd cohort took recess for one year requesting to join back as a part of 3rd cohort commencing one year later, all 51 who continued passed though 3 of them had to resit. All those who passed module 1 (both cohorts) and 2 (1st cohort) registered for their respective next module (return on investment Kirkpatrick level 5). Conclusion: For a successful model in distance learning in clinical transplantation it is imperative for the students to accomplish well defined “critical-decision making” skills. In order to learn critical thresholds, a regular feedback is integral to learning from reflective practice. This course equips the students to develop skills of negotiating “sticky mire”, as obvious from perceived high return of investment

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies

IntroductionIn recent years, the world’s attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications.MethodsThe purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR).Results and DiscussionThe HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles’ surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4’-sulfate showed promise as an anti-cancer metabolite

Neutralizing antibodies against SARS-CoV-2 are higher but decline faster in mRNA vaccinees compared to individuals with natural infection.

Waning protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to the waning of immunity to SARS-COV-2 remains unclear. We aimed to investigate the dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals. We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n = 100) in two phases: phase-I (P-I) at ~ 1.4 and phase-II (P-II) at ~ 5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n = 40) at ~ 1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured. The VN group elicited significantly greater antibody responses (p < 0.001) than the NI group at P-I, except for IgM. In the VN group, a significant waning in antibody response was observed in all isotypes. There was about ~ a 4-fold decline in NTAb levels (p < 0.001), anti-S-RBD-IgG (~5-folds, p < 0.001), anti-S-RBD-IgM (~6-folds, p < 0.001), and anti-S1-IgA (2-folds, p < 0.001). In the NI group, a significant but less steady decline was notable in S-RBD-IgM (~2-folds, p < 0.001), and a much smaller but significant difference in NTAb (<2-folds, p < 0.001) anti-S-RBD IgG (<2-folds, p = 0.005). Unlike the VN group, the NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA, which were ~ 3 folds higher in VN subjects compared to NI in P-1 (p < 0.001), dropped to almost the same levels, with no significant difference observed between the two groups in P-II. While double-dose mRNA vaccination boosted antibody levels, vaccinated individuals' 'boost' was relatively short-lived.This work was made possible by WHO grant numbers COVID-19-22-43 and UREP28–173–3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

Validation of a Novel Fluorescent Lateral Flow Assay for Rapid Qualitative and Quantitative Assessment of Total Anti-SARS-CoV-2 S-RBD Binding Antibody Units (BAU) from Plasma or Fingerstick Whole-Blood of COVID-19 Vaccinees

Background: Limited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). Aim: This study aimed to evaluate the performance of the fluorescence LFA FinecareTM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113) against the following reference methods: (i) the FDA-approved GenScript surrogate virus-neutralizing assay (sVNT); and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®. Methods: Plasma from 488 vaccinees was tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM. Results and conclusions: FinecareTM showed 100% specificity, as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlation r = 0.9, p < 0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r = 0.5, p < 0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralizing antibody (nAb) post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r = 0.6, p < 0.0001) and moderate correlation with VITROS® (r = 0.5, p < 0.0001) and CL-900i® (r = 0.4, p < 0.0001), suggesting that FinecareTM can be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.This work was made possible by grant number UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Corticosteroid minimization in renal transplantation: Careful patient selection enables feasibility

AIM: To explore the benefits and harms of corticosteroid (CS) minimization following renal transplantation. METHODS: CS minimization attempts to improve cardiovascular risk factors (hypertension, diabetes, dyslipidemia), to enhance growth in children, to ameliorate bone disease and to lead to better compliance with immunosuppressive agents. Nevertheless, any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival. RESULTS: Complete CS avoidance or very early withdrawal (i.e., no CS after post-transplant day 7) seems to be associated with better outcomes in comparison with later withdrawal. However, an increased incidence of CS-sensitive acute rejection has been observed with all CS minimization strategies. Among the prerequisites for the safe application of CS minimization protocols are the administration of induction immunosuppression and the inclusion of calcineurin inhibitors in maintenance immunosuppression regimens. CONCLUSION: Transplant recipients at low immunological risk (primary transplant, low panel reactive antibodies) are thought as optimal candidates for CS minimization. CS avoidance may also be undesirable in patients at risk for glomerulonephritis recurrence or with severe delayed graft function and prolonged cold ischemia time. Thus, CS minimization is not yet ready for implementation in the majority of transplant recipients

The Effect of Some Carbonated Beverages on Enamel of Human Premolars (Scanning and Light Microscopic Study)

In modern societies, the increased consumption of soft drinks is becoming more important because of the concern for dental erosion. The aim of the present study is to reveal and compare the possible effect of some carbonated beverages on occlusal and cervical parts of enamel in the buccal surface of human premolars. Twenty sound (caries- free) human maxillary premolars extracted for orthodontic reasons were used in the present study. The teeth were then divided into: Control group: (before immersion in the beverages), in which the collected teeth were immersed at first in tap water and subdivided into 4 subgroups (5 teeth each) and named; Control Sprite, Control Mirinda Orange, Control Coca- Cola and subgroup R. Experimental group: (after immersion in the beverages) in which the first 3 subgroups which were used as control were then utilized as experimental after immersion in the corresponding beverage. They were named; Subgroup S (Sprite experimental Subgroup), Subgroup M (Mirinda Orange experimental Subgroup) and Subgroup C (Coca-Cola experimental Subgroup). The teeth were examined using SEM and light microscope. Morphometric study was performed, using computerized image analyzer for the assessment of affected band thickness. The SEM results of the experimental subgroups revealed that each beverage cause different pattern of erosion. In Subgroup S, the enamel surface was feather like and pitted. In Subgroup M, the enamel surface presented the honeycomb pattern. In Subgroup C, the enamel surface was nearly smooth with generalized structural loss. It was noticed also that the changes in enamel surface became more accentuated toward the cervical third. The light microscopic examination revealed that in both Subgroups S and C the outer enamel layer exhibited dark band of affection, while in Subgroup M this band was translucent. The affection of subsurface and deep enamel layers was noticed in all the experimental subgroups, in addition the changes in enamel became more accentuated toward the cervical third. The morphometric data revealed that the thickness of the affected band in the outer layer of enamel increased toward the cervical third in all experimental subgroups. This band was minimal in Subgroup S, and increased in Subgroup M, followed by Subgroup C. From the present study we can conclude that acidic beverages had deleterious effect on dental hard tissues. Among the investigated drinks of the present work, the Sprite had the least erosive potential, followed by Mirinda Orange, then Coca-Cola which had the most erosive potential. The erosive potential of a beverage was depended on its pH value, titratable acidity, type and concentration of the acid(s) present. Enamel affection for a given beverage was maximum at the cervical third and minimal in the occlusal

Assessment of serum irisin level in thyroid disorder

Background Irisin is a newly discovered myokin secreted by myocytes responsible for transmission of signals from muscles to other body tissues. Irisin improves systemic metabolism by increasing the energy expenditure. Owing to numerous similarities in action between irisin and thyroid hormones it seems imperative to explore these substances’ potential mutual influence on the body. Objective To estimate serum irisin concentration in patients with hypothyroid and hyperthyroid diseases, and to detect the relation of serum irisin in patients with thyroid disorders with creatine kinase (CK), a serum marker of muscle damage. Patients and methods The study comprised 30 hyperthyroid patients (group 1), 30 hypothyroid patients (group 2), and 30 normal persons (group 3). Irisin was measured using enzyme-linked immunosorbent assay. Thyroid-stimulating hormone, triiodothyronine, and free thyroxine levels were measured using chemiluminescent microparticle immunoassay technology. Results Irisin hormone level significantly decreased in hypothyroid patients in comparison with hyperthyroid patients. Irisin hormone level increased in hyperthyroid patients in comparison with normal persons, whereas it decreased in hypothyroid patients in comparison with normal persons. CK level significantly decreased in hyperthyroid patients in comparison with hypothyroid patients. CK level significantly increased in hypothyroid patients in comparison with normal persons, whereas it significantly decreased in hyperthyroid patients in comparison with normal persons. Conclusion Obtained results suggest the influence of thermometabolic state on irisin level

Role of crossmatch testing when Luminex-SAB is negative in renal transplantation

The human leukocyte antigen (HLA) system plays an important role in the acceptance of renal graft. Long and better graft survival has been reported in patients with HLA-identical siblings and a nonreactive cytotoxicity assay (CDC). New methods of HLA-typing and anti-HLA antibody detection techniques such as flow cytometry, solid-phase immunoassays, or antigen bead assays have further improved the outcomes of renal transplant recipients. In the present review, the explicit details of these methodologies are discussed in detail