Synergistic effects of using sodium hypochlorite (bleach) and desiccation in surface inactivation for Toxocara spp.

Toxocara cati and T. canis are parasitic nematodes found in the intestines of cats and dogs respectively, with a cosmopolitan distribution, and the potential for anthropozoonotic transmission, resulting in human toxocariasis. Spread of Toxocara spp. is primarily through the ingestion of embryonated eggs contaminating surfaces or uncooked food, or through the ingestion of a paratenic host containing a third-stage larva. The Toxocara spp. eggshell is composed of a lipid layer providing a permeability barrier, a chitinous layer providing structural strength, and thin vitelline and uterine layers, which combined create a biologically resistant structure, making the Toxocara spp. egg very hardy, and capable of surviving for years in the natural environment. The use of sodium hypochlorite, household bleach, as a disinfectant for Toxocara spp. eggs has been reported, with results varying from ineffective to limited effectiveness depending on parameters including contact time, concentration, and temperature. Desiccation or humidity levels have also been reported to have an impact on larval development and/or survival of Toxocara spp. eggs. However, to date, after a thorough search of the literature, no relevant publications have been found that evaluated the use of sodium hypochlorite and desiccation in combination. These experiments aim to assess the effects of using a combination of desiccation and 10% bleach solution (0.6% sodium hypochlorite) on fertilized or embryonated eggs of T. cati, T. canis, and T. vitulorum. Results of these experiments highlight the synergistic effects of desiccation and bleach, and demonstrate a relatively simple method for surface inactivation, resulting in a decrease in viability or destruction of T. cati, T. canis and T. vitulorum eggs. Implications for these findings may apply to larger scale elimination of ascarid eggs from both research, veterinary, and farming facilities to mitigate transmission.

The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.

This scoping review identifies the mechanistic pathways of metformin when used to treat head and neck cancer cells, in the pre-clinical setting. Understanding the underlying mechanisms will inform future experimental designs exploring metformin as a potential adjuvant for head and neck cancer. This scoping review was conducted according to the Joanna-Briggs Institute framework. A structured search identified 1288 studies, of which 52 studies fulfilled the eligibility screen. The studies are presented in themes addressing hallmarks of cancer. Most of the studies demonstrated encouraging anti-proliferative effects in vitro and reduced tumor weight and volume in animal models. However, a few studies have cautioned the use of metformin which supported cancer cell growth under certain conditions.

Anterior Pedicled Nasal Flap in Frontal Sinus Drill-Out Patients: A Randomised Controlled Pilot Study.

Background: The endoscopic modified Lothrop procedure (EMLP) is a common procedure performed in patients with frontal sinus pathology. While performing this procedure, large segments of bone are exposed, which may lead to the promotion of frontal sinus neo-ostium stenosis. Here we examine the peri-operative differences in time to achieve healing in patients where a mucosal flap is used to cover the exposed bone on one side of the neo-ostium. Design: A randomised pilot study with 12 patients undergoing EMLP surgery participated in this study. Methods: Patients were randomised to undergo a mucosal flap on either the left or right side of the neo-ostium. Prior to surgery, patients completed a SNOT-22 and smell identification test. Patients were reviewed until the neo-ostium had healed on both sides. Once healing had occurred, a post-operative SNOT-22 score and smell identification test were recorded. Results: Average time to healing for the frontal sinus neo-ostium was 4.7 vs. 4.2 (p = 0.3) on the flap vs. non-flap side, respectively. There was an average 24.4 point (range: -75 to +9) decrease in SNOT-22 scores post-surgery. The post-operative USPIT score demonstrated an average increase of 6.6 points (range -13 to +27). Conclusion: We did not detect significant differences in peri-operative time toward healing in neo-ostiums where a single flap is utilised. Further studies are needed to determine whether the usage of a single neo-ostium flap affords any benefit over no flap on either ostium. SNOT-22 and UPSIT scores improved post-surgery.

Risk of airway fire with the use of KTP laser and high flow humidified oxygen delivery in a laryngeal surgery model.

Airway surgery presents a unique environment for operating room fire to occur. This study aims to explore the factors of combustion when using KTP laser with high flow oxygen in an ex-vivo model. The variables tested were varying tissue type, tissue condition, oxygen concentration, laser setting, and smoke evacuation in a stainless-steel model. Outcome measures were time of lasing to the first spark and/or flame. A multivariate Cox proportional hazard model was used to determine the risk of spark and flame across the different risk factors. For every 10% increase in oxygen concentration above 60% the risk of flame increased by a factor of 2.3. Continuous laser setting at 2.6 W increased the risk by a factor of 72.8. The risk of lasing adipose tissue is 7.3 times higher than that of muscle. Charred tissue increases the risk of flame by a factor of 92.8. Flame occurred without a preceding spark 93.6% of the time. Using KTP laser in the pulsed mode with low wattages, minimising lasing time, reducing the oxygen concentration and avoiding lasing adipose or charred tissue produce a relatively low estimated risk of spark or flame.

Health Related Quality of Life T-14 Outcomes for Pediatric Bizact Tonsillectomy.

Objectives: The objective of this study was to assess the T-14 outcomes of the BizactTM device for tonsillectomy in a pediatric population. Methods: A case series chart review was undertaken at a public tertiary teaching hospital and private otolaryngology practice, with data collected from pediatric patients who underwent a BizactTM tonsillectomy between July 2016 and October 2019 for any indication, whose parents consented to completing the T-14 questionnaire providing a parental perspective of the child's quality of life. Primary outcomes were T-14 scores recorded preoperatively and 6 weeks post-operatively. Secondary outcome measures were postoperative complications, including hemorrhage and readmission. Results: 146 patients were identified. There was a significant improvement in T-14 scores from a median of 24 (Interquartile range (IQR) 18-33) prior to surgery to 2 (IQR 0-4) at 6 weeks postoperatively (p < 0.001). The post-tonsillectomy hemorrhage rate was 6.1% (9/146 participants). Conclusions: Pediatric BizactTM tonsillectomy is effective in treating common indications for pediatric tonsillectomy, reflected by improved parent-reported health-related quality of life T-14 scores postoperatively.

Intranasal immunization with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses.

Mycobacterium tuberculosis (Mtb) remains a global epidemic despite the widespread use of Bacillus Calmette-Guérin (BCG). Consequently, novel vaccines are required to facilitate a reduction in Mtb morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food-grade bacterium Lactococcus lactis that is used to express selected peptides engineered within the Streptococcus pyogenes M1T1 pilus, allowing for peptide amplification, stabilization and enhanced immunogenicity. In the present study, the dominant T-cell epitope from the Mtb protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of L. lactis. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B-cell responses in intranasally vaccinated mice were analyzed by ELISA while T-cell responses were analyzed by flow cytometry. Serum titers of peptide-specific immunoglobulin (Ig) G and IgA were detected, confirming that vaccination produced antibodies against the cognate peptide. Peptide-specific IgA was also detected across several mucosal sites sampled. Peptide-specific CD4+ T cells were detected at levels similar to those of mice immunized with BCG. PilVax immunization resulted in an unexpected increase in the numbers of CD3+ CD4- CD8- [double negative (DN)] T cells in the lungs of vaccinated mice. Analysis of cytokine production following stimulation with the cognate peptide showed the major cytokine producing cells to be CD4+ T cells and DN T cells. This study provides insight into the antibody and peptide-specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study.

On the heterozygosity of an admixed population.

In this study, we consider admixed populations through their expected heterozygosity, a measure of genetic diversity. A population is termed admixed if its members possess recent ancestry from two or more separate sources. As a result of the fusion of source populations with different genetic variants, admixed populations can exhibit high levels of genetic diversity, reflecting contributions of their multiple ancestral groups. For a model of an admixed population derived from K source populations, we obtain a relationship between its heterozygosity and its proportions of admixture from the various source populations. We show that the heterozygosity of the admixed population is at least as great as that of the least heterozygous source population, and that it potentially exceeds the heterozygosities of all of the source populations. The admixture proportions that maximize the heterozygosity possible for an admixed population formed from a specified set of source populations are also obtained under specific conditions. We examine the special case of [Formula: see text] source populations in detail, characterizing the maximal admixture in terms of the heterozygosities of the two source populations and the value of [Formula: see text] between them. In this case, the heterozygosity of the admixed population exceeds the maximal heterozygosity of the source groups if the divergence between them, measured by [Formula: see text], is large enough, namely above a certain bound that is a function of the heterozygosities of the source groups. We present applications to simulated data as well as to data from human admixture scenarios, providing results useful for interpreting the properties of genetic variability in admixed populations.

A review of the use of transnasal humidified rapid insufflation ventilatory exchange for patients undergoing surgery in the shared airway setting.

Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) is a recent technique that delivers warm humidified high flow oxygen to patients, allowing for prolonged apneic oxygenation. A review of current literature was performed to determine the use of THRIVE in apneic patients undergoing surgery in a shared airway setting. An initial free hand search was done to identify keywords followed by a systematic search of major databases with no date or language restrictions. Inclusion criteria include all apneic patients who receive THRIVE for any operative procedure. Fifteen studies fulfilled the inclusion criteria. There were ten case series, two case reports, two review articles and one randomized controlled trial. All of the studies discussed the use of THRIVE during laryngopharyngeal surgeries. The median apnea time reported ranged between 13 and 27 min. There were no significant complications reported as a result of using THRIVE. Most studies identified in this review were observational in nature involving laryngopharyngeal procedures. They have demonstrated THRIVE to be effective in providing apneic oxygenation during short procedures in adult patients. Further studies are required to determine the limitations of safe use in specific populations and when THRIVE is combined with diathermy or laser use.

Genotype imputation in a coalescent model with infinitely-many-sites mutation.

Empirical studies have identified population-genetic factors as important determinants of the properties of genotype-imputation accuracy in imputation-based disease association studies. Here, we develop a simple coalescent model of three sequences that we use to explore the theoretical basis for the influence of these factors on genotype-imputation accuracy, under the assumption of infinitely-many-sites mutation. Employing a demographic model in which two populations diverged at a given time in the past, we derive the approximate expectation and variance of imputation accuracy in a study sequence sampled from one of the two populations, choosing between two reference sequences, one sampled from the same population as the study sequence and the other sampled from the other population. We show that, under this model, imputation accuracy-as measured by the proportion of polymorphic sites that are imputed correctly in the study sequence-increases in expectation with the mutation rate, the proportion of the markers in a chromosomal region that are genotyped, and the time to divergence between the study and reference populations. Each of these effects derives largely from an increase in information available for determining the reference sequence that is genetically most similar to the sequence targeted for imputation. We analyze as a function of divergence time the expected gain in imputation accuracy in the target using a reference sequence from the same population as the target rather than from the other population. Together with a growing body of empirical investigations of genotype imputation in diverse human populations, our modeling framework lays a foundation for extending imputation techniques to novel populations that have not yet been extensively examined.

Haplotype variation and genotype imputation in African populations.

Sub-Saharan Africa has been identified as the part of the world with the greatest human genetic diversity. This high level of diversity causes difficulties for genome-wide association (GWA) studies in African populations-for example, by reducing the accuracy of genotype imputation in African populations compared to non-African populations. Here, we investigate haplotype variation and imputation in Africa, using 253 unrelated individuals from 15 Sub-Saharan African populations. We identify the populations that provide the greatest potential for serving as reference panels for imputing genotypes in the remaining groups. Considering reference panels comprising samples of recent African descent in Phase 3 of the HapMap Project, we identify mixtures of reference groups that produce the maximal imputation accuracy in each of the sampled populations. We find that optimal HapMap mixtures and maximal imputation accuracies identified in detailed tests of imputation procedures can instead be predicted by using simple summary statistics that measure relationships between the pattern of genetic variation in a target population and the patterns in potential reference panels. Our results provide an empirical basis for facilitating the selection of reference panels in GWA studies of diverse human populations, especially those of African ancestry.

Genome-wide association studies in diverse populations.

Genome-wide association (GWA) studies have identified a large number of SNPs associated with disease phenotypes. As most GWA studies have been performed in populations of European descent, this Review examines the issues involved in extending the consideration of GWA studies to diverse worldwide populations. Although challenges exist with issues such as imputation, admixture and replication, investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.

The relationship between imputation error and statistical power in genetic association studies in diverse populations.

Genotype-imputation methods provide an essential technique for high-resolution genome-wide association (GWA) studies with millions of single-nucleotide polymorphisms. For optimal design and interpretation of imputation-based GWA studies, it is important to understand the connection between imputation error and power to detect associations at imputed markers. Here, using a 2x3 chi-square test, we describe a relationship between genotype-imputation error rates and the sample-size inflation required for achieving statistical power at an imputed marker equal to that obtained if genotypes at the marker were known with certainty. Surprisingly, typical imputation error rates (approximately 2%-6%) lead to a large increase in the required sample size (approximately 10%-60%), and in some African populations whose genotypes are particularly difficult to impute, the required sample-size increase is as high as approximately 30%-150%. In most populations, each 1% increase in imputation error leads to an increase of approximately 5%-13% in the sample size required for maintaining power. These results imply that in GWA sample-size calculations investigators will need to account for a potentially considerable loss of power from even low levels of imputation error and that development of additional genomic resources that decrease imputation error will translate into substantial reduction in the sample sizes needed for imputation-based detection of the variants that underlie complex human diseases.

Genotype-imputation accuracy across worldwide human populations.

A current approach to mapping complex-disease-susceptibility loci in genome-wide association (GWA) studies involves leveraging the information in a reference database of dense genotype data. By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples can be imputed and tested for disease association. This imputation strategy has been successful for GWA studies in populations well represented by existing reference panels. We used genotypes at 513,008 autosomal single-nucleotide polymorphism (SNP) loci in 443 unrelated individuals from 29 worldwide populations to evaluate the "portability" of the HapMap reference panels for imputation in studies of diverse populations. When a single HapMap panel was leveraged for imputation of randomly masked genotypes, European populations had the highest imputation accuracy, followed by populations from East Asia, Central and South Asia, the Americas, Oceania, the Middle East, and Africa. For each population, we identified "optimal" mixtures of reference panels that maximized imputation accuracy, and we found that in most populations, mixtures including individuals from at least two HapMap panels produced the highest imputation accuracy. From a separate survey of additional SNPs typed in the same samples, we evaluated imputation accuracy in the scenario in which all genotypes at a given SNP position were unobserved and were imputed on the basis of data from a commercial "SNP chip," again finding that most populations benefited from the use of combinations of two or more HapMap reference panels. Our results can serve as a guide for selecting appropriate reference panels for imputation-based GWA analysis in diverse populations.