This is an invited editorial of an article to be published in the Jouranl of Cardiac Surgery

A potential immunological silver bullet for COVID-19: the trivalent chimpanzee adenoviral serotype-68 vector (Tri:ChAd)

Background: World-wide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) in children has been increasing in past decades. Association between the two diseases has been found in some but not other studies. Objective: We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships. Methods: Three databases (PubMed, Embase and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between single-nucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse variance-weighted, weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test was conducted. Results: In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR=1.30, 95% CI 1.05-1.61, P=0.014), whereas T1DM was not associated with the risk of asthma (HR=0.98, 95% CI 0.64-1.51, P=0.941; OR=0.84, 95% CI 0.65-1.08, P=0.168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR=1.308; 95% CI 1.030-1.661; P =0.028). Analysis using the IVW method indicated not associated between T1DM and genetic risk of asthma (OR=1.027, 95%CI 0.970-1.089, P=0.358). Conclusion: Both meta-analysis and MR study suggested that childhood asthma was a risk factor for T1DM. No epidemiological or genetic evidence for an association of T1DM with asthma incidence. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM.

Ameloblastoma is a benign jaw tumor that can grow to a very huge size with high rate of recurrence. The large tumours pose a challenge during resection and reconstructive surgery. We present a massive ameloblastoma of the mandible that was surgically treated with the aid of 3D printed model.

We report on a child with prenatal findings of increased nuchal translucency, polydramnios, ascites and overgrowth. At birth she presented length >97° centile, minor facial anomalies, megalencephaly and Wolff-Parkinson-White syndrome. Whole Exome Sequencing showed a pathogenic variant in the NRAS gene, but no mutations were found in PI3K/AKT/mTOR pathway genes.

A document by Muhammad Haris Farooq. Click on the document to view its contents.

Understanding the heterogeneity of “mitral atresia” with patent aortic root

Choosing to perform mitral valve (MV) repair or replacement remains a hot and highly debated topic. The current guidelines seem to be conflicting in this specific field and the evidences at our disposal are scarce, only one small randomized trial and few larger retrospective studies. The meta-analysis by Gamal and coworkers tries to summarize the current evidences, concluding that MV replacement for the treatment of ischemic mitral regurgitation is at least as safe as repair and certainly offers a more stable result over time than the latter. Obviously, the implantation of a prosthesis, especially a mechanical one, brings with it a series of problems, such as anticoagulation and, above all, a possible lack of ventricular remodeling, especially if a chordal sparing replacement is not performed. It must be said, on the other hand, that isolated annuloplasty cannot act as a counterpart to replacement, because ischemic MR cannot be considered only an annular disease. Therefore, wanting to mimic the nature that, after an infarction, enacts a series of changes involving also the mitral leaflets and chordae, the surgeons are called to act also on these two entities and not only to downsize the annulus. In a nutshell, a procedure should not be opposed in a fundamentalist way to another one, but we must accept the concept of armamentarium where both procedures are present and tail on the single patient, and also on the surgeon’s expertise, the technique guaranteeing the best possible result.

Ecological restoration of former agricultural land can improve soil condition, recover native vegetation, and provide fauna habitat. However, restoration benefits are often associated with time lags, as many attributes, such as leaf litter and coarse woody debris, need time to accumulate. Here we experimentally tested whether adding fine and coarse woody debris to a decade-old restoration sites can accelerate restoration benefits. We used a Multi-site Before-After / Control-Impact design to test the effects on 30 response variables over a period of two years, including those describing soil physical and biochemical properties, herbaceous vegetation and ant communities. We analysed the data using linear mixed-effect models and perMANOVAs. Of the 30 response variables, a significant effect of mulch or log additions was found for just four variables: volumetric water content, decomposition of tea leaves, native herbaceous species cover and species richness of opportunistic ants. Mulch addition had a positive effect on soil moisture when compared to controls but suppressed growth of native (but not exotic) herbaceous plants. Whilst other soil properties such as organic matter and dissolved organic carbon showed a positive response to mulch addition, the effect was not statistically significant. On plots with log additions, decomposition rates of tea leaves decreased, and species richness of opportunistic ants increased. However, we found no effect on total species richness and abundance of other ant functional groups. The benefit of mulch to soil moisture was offset by its disbenefit to native herbs in our study. Logs increased species richness of opportunistic ants, but given time, may provide habitat for cryptic species. Indeed, benefits to other soil biophysical properties, vegetation and ant fauna may require longer timeframes to be detected. Further research is needed to determine whether the type, quantity and context of mulch and log additions may improve restoration outcomes.

Objective : This study aims to compare the potential sinus distribution between high-volume nasal irrigation and nasal spray in chronic rhinosinusitis patients who have not undergone sinus surgery. Design and Setting : A randomized clinical study was conducted at the Otolaryngology-Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University.Participants : 40 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis. Thirty-eight patients met the inclusion criteria and were randomly assigned to receive nasal irrigation or nasal spray mixed with fluorescein sodium preoperatively. Main outcome measures : The primary outcome was the mean difference in the staining score of fluorescein in all sinuses between the two groups. Results : The total staining score of fluorescein in all sinuses via nasal irrigation was statistically more significant than the score via nasal spray, with a mean difference score of 2.90, 95%CI: 1.22-4.58, p-value 0.001. The most significantly affected sinuses were specific to the maxillary and anterior ethmoid sinuses, whereas the frontal and sphenoid sinuses had the slightest solution distribution from both techniques. Conclusion : Nasal irrigation is a potential route to deliver drugs into the sinus in unoperated CRS patients. However, it is not considered a superior method to nasal spray at the most challenging anatomical areas, i.e., the frontal and sphenoid sinuses. Keywords : Corticosteroid use, Endoscopic sinus surgery, Irrigations, Topical therapy for chronic rhinosinusitis, Medical therapy for chronic rhinosinusitis, Nasal polyp, Nasal spray, Chronic rhinosinusitis

Immobilized enzymes have drawn widespread attention due to the enhanced stability, easy separation from reaction mixture, and the prominent recyclability. Nevertheless, it is still an ongoing challenge to develop potent immobilization techniques which are capable of stable enzyme encapsulation, minimal loss of activity, and modulability for various enzymes and applications. Here, microfibers with tunable size and composition were fabricated using a home-made microfluidic device. These microfibers were able to efficiently encapsulate bovine serum albumin (BSA), glucose oxidase (GOX) and horseradish peroxidase (HRP). But the physically adsorbed enzymes readily diffused from microfibers into the catalytic reaction system. The leakage of enzymes could be substantially inhibited by conjugating to polyacrylic acid (PAA) and incorporating into the alginate-based microfibers, enabling stable immobilization, improved recyclability, and enhanced thermostability. In addition, GOX and HRP-loaded microfibers were fabricated under the optimized conditions for the visual detection of glucose using the cascade reaction of these enzymes, showing sensitive color change to glucose with concentration range of 0-2 mM. Due to the tunability and versatility, this microfluidic-based microfiber platform may provide a valuable approach to the enzyme immobilization for the cascade catalysis and diagnoses with multiple clinical markers.

The chloroplast represents an attractive compartment for light-driven biosynthesis of recombinant products, and advanced synthetic biology tools are available for engineering the chloroplast genome (=plastome) of several algal and plant species. However, producing commercial lines will likely require several plastome manipulations, and this will present issues with respect to selectable markers: there are a limited number of markers available, these can be used only once in a serial engineering strategy, and it is undesirable to retain marker genes for antibiotic resistance in the final transplastome. To address these problems, we have designed a rapid iterative marker system for the green microalga Chlamydomonas reinhardtii that allows creation of marker-free transformants starting from wild-type strains. The system employs a dual marker encoding a fusion protein of E. coli aminoglycoside adenyltransferase (conferring spectinomycin resistance) and a variant of E. coli cytosine deaminase (conferring sensitivity to 5-fluorocytosine). Initial selection on spectinomycin allows stable transformants to be established and driven to homoplasmy. Subsequent selection on 5-fluorocytosine results in rapid loss of the dual marker through intramolecular recombination between the marker’s 3’UTR and the 3’UTR of the introduced transgene(s). We demonstrate the versatility of the CpPosNeg system by serial introduction of reporter genes into the plastome.

The rapid intensification of the livestock sector in Southeast Asia has been found to be associated with an extensive and expanding use of antibiotics. This raises concerns regarding the rise of drug-resistant bacteria in both animals and humans. Data on veterinary antibiotic use (ABU) and antibiotic resistance (ABR) are scarce in Lao PDR, as in most low and middle-income countries. This study aimed to explore the views of small to medium-scale pig, poultry and fish producers regarding the use of antibiotics. A total of 364 farmers were surveyed using a questionnaire and farm visits. Patterns of knowledge, attitudes and practices regarding ABU and ABR were explored with multiple factor analysis and hierarchical cluster analysis. Farms were assigned to one of three clusters in which specific farmers’ views were overrepresented. Cluster 1 (in which pig farms were overrepresented) held a positive attitude regarding preventive measures and information about antibiotics. In cluster 2 (in which poultry farms were overrepresented), there was a view that antibiotics should be used for disease prevention. Finally, in cluster 3 (in which fish farms were overrepresented), knowledge about ABU and ABR was weak, and ABU was very limited. No specific attitude was under or overrepresented. Farmers mentioned that they were unfamiliar with antibiotics and were uncertain about details concerning ABR (such as whether or not to consume animal products just after they received antibiotic treatment). Farmers from cluster 3 who did not give antibiotics to their animal (90 out of 114) and did not use vaccines (100 out of 114) were overrepresented. A total of 65% (171/263) of the antibiotics found on farms were included on the World Health Organization’s list of critically important antibiotics for human medicine. These critically important antibiotics were mostly found in clusters 1 (57/168, i.e., 33.8% farms had at least one critically important antibiotic) and 2 (63/171, 36.8%). These findings indicate that antibiotic stewardship strategies should tackle the use of critical antibiotics as well prophylactic treatments to prevent antibiotic misuse in small and medium- livestock farms.

Introduction: Lower socioeconomic status is associated with significantly poorer outcomes in weight, lung function, and pulmonary exacerbation rates in People with CF (PwCF). Global aim: We aim to reduce health disparities and inequities faced by PwCF by screening for and addressing unmet social needs. Specific aims: We aimed to increase routine Social Determinants of Health (SDoH) screening of eligible PwCF from 0% to 95% and follow-up within two weeks for those PwCF who screened positive and requested assistance from 0% to 95% by December 31, 2021. Methods: The Model for Improvement methodology was employed. A process map and a simplified failure mode effects analysis chart were created for the screening and SDoH follow-up process. Those who screened positive for SDoH and requested assistance, a follow-up contact was made to offer intervention. Intervention: Adult PwCF who had at least one UVA Clinic encounter in 2021 were screened for SDoH. The SDoH screening tool included eight domains: housing, food, transportation, utilities, health-care access, medication access, income/employment and education. Follow-up was completed with all PwCF who screened positive for SDoH. Results: A total of 132 of 142, (93.0%) PwCF eligible for screening completed the SDoH screening. Of the PwCF who completed screening, 56 (42.4%) screened positive for SDoH. A follow-up rate of 100% was achieved in June 2021 and maintained through December 2021. Conclusion: Implementing screening for SDOH and follow-up to mitigate social difficulties in adult PwCF at UVA was successful and could be reproduced at other CF care center.

A two-step integrated MOF and pressure/vacuum swing adsorption (P/VSA) process design has been recently established for gas separation. In the first step, selected MOF descriptors and process operating conditions are simultaneously optimized to maximize the process performance. Based on the obtained results, the second step (i.e., MOF matching) is addressed and exemplified by propene/propane separation in this work. Computational MOF synthesis and screening are carried out to find new advanced material candidates for enhancing the separation process efficiency. First, model-based property-performance relationships are developed for fast MOF screening. Then, MOF building blocks are extracted from 471 CoRE MOFs. With these building blocks, 45472 hypothetical MOFs are created. After model-based and molecular simulation-based screening, six candidates are left and sent to P/VSA process optimization. Finally, three candidates are found to meet the pre-defined separation specifications and one candidate shows a better process performance than the best out of the 471 MOFs.

Objective: To evaluate whether prolonged operative time is negatively associated with post-operative complications and length of stay in patients undergoing microvascular free flap reconstruction for complex head and neck defects. Methods: 342 consecutive patients undergoing microvascular reconstruction for head and neck defects between 2017-2019 at a single institution were evaluated. Operative outcomes and operative time were compared whilst controlling for patient and treatment related factors. Results: Mean operative time was 551 minutes and length of stay was 16.2 days. An 11% increase in the risk of a post-operative complication was observed for every additional hour of operative time (OR 1.11, 95%CI 1.03 – 1.21, p=0.011) after adjusting for patient and treatment factors. A cut-off of 9 hours yielded a 92% increase in complications on either side of this (OR 1.92, 95%CI 1.18 – 3.13, p=0.009). Increased operative time was also associated with increased length of stay and return to theatres, but not medical complications. Conclusion: Prolonged operative time is significantly associated with increase surgical complications, length of stay and return to theatres when performing microvascular reconstructive surgery for head and neck defects. Keywords : free flap, microsurgery, operative time, length of hospital stay, complication rate, head and neck surgery Key points : 1. This study analyzed a contemporary cohort over a relatively short period where outcomes can reliably be recorded and verified 2. This is the first Australian study that demonstrated operative time as it relates to surgical technique, comparing pedicled and free flaps and also stratified by flap type, oncological resection, or comorbidity 3. Operations more than 9 hours duration were associated with an 89% increase in the odds of developing a surgical complication 4. Prolonged operative time was also significantly associated with length of stay and return to theatres 5. Future studies are needed to investigate associations with each component of operative time element separately in a multi institutional design

Soil is the largest carbon reservoir in terrestrial ecosystems, and thus minor changes in it can dramatically affect atmospheric CO 2 concentrations. The fragile ecological environment in the northwestern arid zone of China is susceptible to natural and anthropogenic disturbances, which lead to variations in structure and function of the ecosystem, as well as carbon source–sink dynamics. In this study, digital soil maps of soil organic carbon stocks (SOCS) were produced at a 90-m resolution for two periods (the 1980s and 2010s) based on historical soil profile data and a random forest model. The results showed that the prediction accuracy for SOCS in the topsoil (0–30 cm) was superior to that of the subsoil (30–100 cm). Among them, the mean annual evapotranspiration, normalized difference vegetation index during the growing season, multi-year mean temperature, and clay content were the main environmental factors affecting the spatial distribution of SOCS. In the past 30 years, the SOCS of the northwestern arid zone have decreased by 585.50 Tg, with a mean decline of 19.52 Tg C yr -1. The changes in SOCS caused by land-use conversion and reductions in SOCS were further shown to be attributable to grassland desertification and agricultural reclamation. These findings are valuable for exploring the carbon cycle in terrestrial ecosystems in the context of global climate change and for achieving China’s goal of carbon neutrality.

Introduction Otoscopy is a key clinical skill which following the introduction of the Medical Licensing Assessment all newly qualified doctors in the United Kingdom will be required to be able to perform independently. At present there is no consensus on a standardised method for objectively assessing otoscopy skills. Methods Prospective mixed methods study comparing face, content and construct validity of three different platforms for otoscopy skills assessment, using a traditional otoscope with manikin, digital otoscope (Tympahealth) with manikin, and traditional otoscope with a low-cost model ear (SimEar). Skills were assessed using a standardised mark scheme, and five expert assessors and twelve participants who rotated through three Objective Structured Clinical Examination (OSCE) stations representing each model. Assessors numerically ranked validity of each model, and participated in a semi-structured interview of opinion. Results Each platform differed in face, construct and content validity scores, with no one platform consistently outperforming others. Three main themes were identified during thematic analysis of expert assessor interviews: ability to assess what is seen, anatomical reality, and ease of use. The low-cost model showed greatest potential, where modification to include a silicone ear could lead to high validity with marginal increase in cost. Conclusion Several modalities for assessing otoscopy skills exist, each with advantages and disadvantages. Modifications to a low-cost model, for use with either a traditional or digital otoscope, could prove to be the best model.