Estimating the test-adjusted incidence of Chlamydia trachomatis infections identified through Public Health Ontario Laboratories in Peel region, Ontario, 2010-2018: a population-based study.

BACKGROUND: Public health guidelines for chlamydia testing are not sex specific, but young females test at a disproportionally higher rate than males and other age groups. This study aims to describe testing trends across age and sex subgroups, then estimate a test-adjusted incidence of chlamydia in these subgroups to identify gaps in current testing practices. METHODS: We used a population-based study to examine observed chlamydia rates by age and sex subgroups: 15-19 years, 20-29 years, 30-39 years and older than 40 years. The study included diagnostic test results recorded by Public Health Ontario Laboratories between Jan. 1, 2010, and Dec. 31, 2018, for individuals living in Peel region, Ontario. We then employed meta-regression models as a method of standardization to estimate the effect of sex and age on standardized morbidity ratio, testing ratio and test positivity, then calculate a test-adjusted incidence of chlamydia for each subgroup. RESULTS: Over the study period, infection, testing and test positivity varied across age and sex subgroups. Observed incidence and testing were highest in females aged 20-29 years, whereas males had the highest standardized test positivity across all age groups. After estimating test-adjusted incidence for each age-sex subgroup, males in the 15-19-year and 30-39-year age groups had an increase in incidence of 60.2% and 9.7%, respectively, compared with the observed incidence. INTERPRETATION: We found that estimated test-adjusted incidence was higher than observed incidence in males aged 15-19 years and 30-39 years. This suggests that infections in males are likely being missed owing to differential testing, and this may be contributing to the persistent increase in reported cases in Canada. Public health programming that targets males, especially in high-risk settings and communities, and use of innovative partner notification methods could be critical to curbing overall rates of chlamydia.

Two nondimensional parameters for characterizing the nuclear morphology.

Nuclear morphology is an important indicator of cell function. It is regulated by a variety of factors such as the osmotic pressure difference between the nucleoplasm and cytoplasm, cytoskeletal forces, elasticity of the nuclear envelope and chromosomes. Nucleus shape and size are typically quantified using multiple geometrical quantities that are not necessarily independent of one another. This interdependence makes it difficult to decipher the implications of changes in nuclear morphology. We resolved this by analyzing nucleus shapes of populations for multiple cell lines using a mechanics-based model. We deduced two independent nondimensional parameters, namely, flatness index and isometric scale factor. We show that nuclei in a cell population have similar flatness but variable scale factor. Furthermore, nuclei of different cell lines segregate according to flatness. Cellular perturbations using biochemical and biomechanical techniques suggest that the flatness index correlates with actin tension and the scale factor anticorrelates with elastic modulus of nuclear envelope. We argue that nuclear morphology measures such as volume, projected area, height etc., are subsumed by flatness and scale factor, which can unambiguously characterize nuclear morphology.

Anti-tumor effects of Artemisia nilagirica extract on MDA-MB-231 breast cancer cells: deciphering the biochemical and biomechanical properties via TGF-ß upregulation.

PURPOSE: Artemisia nilagirica (AN), which is known to have antimicrobial, antioxidant, antiulcer, and anti-asthmatic properties, has been recently shown to have anti-cancer activity. However, the mechanism responsible for the anti-cancer property and its effect on cellular properties and functions are not known. MATERIAL AND METHODS: We have characterized the biochemical and biomechanical properties of MDA-MB-231 cells treated with the methanolic extract from AN. RESULTS: We show that AN-treatment decreases cell-eccentricity, increases expression of actin and microtubules, and do not affect cell-area. Increased expression of cytoskeletal proteins is known to change the mechanical properties of the cells, which was confirmed using micropipette aspiration and Atomic Force Microscopy. We identified the upregulation of the tumorigenic pathway (TGF-ß) leading to activation of Rho-A as the molecular mechanism responsible for actin upregulation. Since the initial stages of TGF-ß upregulation are known to suppress tumor growth by activating apoptosis, we hypothesized that the mechanism of cell death due to AN-treatment is through TGF-ß activation. We have validated this hypothesis by partially recuing cell death through inhibition of TGF-ß using Alk-5. CONCLUSION: In summary, our study reveals the mechanism of action of Artemisia nilagirica using a synergy between biochemical and biomechanical techniques.

A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication.

Morphology of the nucleus is an important regulator of gene expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, nondimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters, such as projected area, surface area, and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to hepatitis C virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed downregulation of lamin-A,C and upregulation of ß-actin, corroborating the predictions of the model. Our modeling assumptions are broadly applicable to adherent, monolayer cell cultures, making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Toward this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.

A Scalable Perfusion Culture System with Miniature Peristaltic Pumps for Live-Cell Imaging Assays with Provision for Microfabricated Scaffolds.

We present a perfusion culture system with miniature bioreactors and peristaltic pumps. The bioreactors are designed for perfusion, live-cell imaging studies, easy incorporation of microfabricated scaffolds, and convenience of operation in standard cell culture techniques. By combining with miniature peristaltic pumps-one for each bioreactor to avoid cross-contamination and to maintain desired flow rate in each-we have made a culture system that facilitates perfusion culture inside standard incubators. This scalable system can support multiple parallel perfusion experiments. The major components are fabricated by three-dimensional printing using VeroWhite, which we show to be amenable to ex vivo cell culture. Furthermore, the components of the system can be reused, thus making it economical. We validate the system and illustrate its versatility by culturing primary rat hepatocytes, live imaging the growth of mouse fibroblasts (NIH 3T3) on microfabricated ring-scaffolds inserted into the bioreactor, performing perfusion culture of breast cancer cells (MCF7), and high-magnification imaging of hepatocarcinoma cells (HuH7).

Epidemic meticillin-resistant Staphylococcus aureus (EMRSA-15) variants detected in healthy and diseased individuals in India.

This study provides what we believe to be the first report of the presence of EMRSA-15 and its variants isolated from nasal swabs from 13 healthy and diseased individuals in India. The majority of the isolates belonged to staphylococcal cassette chromosome mec (SCCmec) type IV and spa type t852, whilst four isolates were non-typable and heterotypic for the presence of the mecA gene. All non-typable isolates were positive for the orfX gene by PCR and belonged to spa types t005 and t2986. They may have variant SCCmec cassettes indicating genetic changes occurring in the Indian EMRSA-15. All isolates were positive for Panton-Valentine leukocidin and toxic shock syndrome toxin, which is a cause for concern. In addition to soft-tissue infections, the EMRSA-15 isolates from patients were also responsible for meningitis and brain abscesses, which is quite rare.

The uniqueness of the human anterior dentition: a geometric morphometric analysis.

The analysis of bitemarks has a significant bearing on forensic odontology and has attracted an increasingly sophisticated array of techniques in its evaluation. Two postulates underlie all bitemark analyses: firstly, that the characteristics of the anterior teeth involved in the bite are unique, and secondly, that this uniqueness is accurately recorded in the material bitten. Here, we investigate the question of the uniqueness of the anterior dentition. To do this, we use geometric morphometric techniques based on landmark and semilandmark data. The incisor and canine occlusal surfaces of 50 randomly selected orthodontic casts of young individuals (17-20 years) of both sexes form the material for this study. We analyzed the sizes of these teeth by means of landmark and semilandmark analysis to calculate Procrustes distances between tooth outlines. In order to analyze shape variation among individuals, we carried out principal components analyses on the partial warp scores. These are derived from Partial Procrustes coordinates aligned by means of thin-plate spline decomposition based on the bending energy matrix. The results indicate that there is no sexual dimorphism in the shape of the upper or lower arches. Plots of centroid size and first relative warps show less superposition among individuals than in shape analysis. This means that, when the size and shape are considered together, the difference between arches increases. Procrustes superimposition between the two individuals located most closely (0.0444) and the two most separated (0.1567) along the first axis of relative warp analyses show that individuals are not only differentiated by the relative position of their teeth but also by their arch shape. In conclusion, it appears that the incisal surfaces of the anterior dentition are in fact unique.