Candida glabrata, an opportunistic fungal pathogen, adheres to mammalian epithelial cells; adherence is mediated primarily by the Epa1 adhesin. EPA1 is a member of a large gene family of $23 paralogues, which encode putative adhesins. In this study, we address how EPA1 transcription is regulated. Our data show that EPA1 expression is subject to two distinct negative regulatory mechanisms. EPA1 transcription is repressed by subtelomeric silencing: the Sir complex (Sir2-Sir4), Rap1, Rif1, yKu70, and yKu80 are required for full repression. Activation of EPA1 occurs immediately after dilution of stationary phase (SP) cells into fresh media; however, transcription is rapidly repressed again, limiting expression to lag phase, just as the cells exit stationary phase. This repression following lag phase requires a cis-acting regulatory negative element (NE) located in the EPA1 39-intergenic region and is independent of telomere proximity. Bioinformatic analysis shows that there are 10 copies of the NE-like sequence in the C. glabrata genome associated with other EPA genes as well as non-EPA genes.
Objective: To identify the diagnostic concordance in the interpretation of cervical smears. Material and Methods: Cross-sectional study from October 2011 to January 2013. 50 samples were read by every 4 cyto-technologists who are the total staffs that read and interpret cytological specimens from a public health institution of the city of San Luis Potosí, México. The cytological diagnosis was confirmed by a certified pathologist. Checklist was developed to determine the quality of the interpretation composed of three sections: adequate sample, inadequate sample and cytological diagnosis. The diagnostic report was made by Bethesda System 2001 classification. Diagnostic concordance was measured through the Kappa coefficient. To establish the differences in cytological diagnosis between each cyto-technologist, chi square test was applied. Results: The concordance is acceptable in the classification of samples as inadequate (k = 0.66). The negative diagnosis was a significant concordance between each cytotechnologist and pathologist; however, no case had very good concordance. In the epithelial abnormalities, only the cytotechnologist 2 had significant concordance with the pathologist, however, its concordance is low. In the case of glandular abnormalities, only cytotechnologist 1 had no significant concordance with the pathologist. The percentage of true negatives was 30%, true positives 20%, false negatives 50% and false positives 0 %. There are significant differences between the readings of cyto-technologist 1 and 2 (p < 0.008), between 1 to 4 (p < 0.001), between 2 and 3 (p < 0.05), and finally between 3 and 4 (p < 0.003). Conclusions: The concordance between cyto-technologists and pathologists is below the required minimum level set by national and international standards.
Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/rRIJg1MEv9k Aim: Cervical cancer (CC) is considered as a major public health problem; this disease affects mainly vulnerable women in poverty, causing a negative effect on a country's workforce. Objective: To determine the histopathological diagnosis variation after examining three more levels of cervical biopsy paraffin blocks from patients with HPVI, CIN and CC. Materials and Methods: A quantitative, retrospective correlational study was performed in a hospital with a second level of health care. We worked with 152 paraffin blocks of CIN (CIN, I, II and III) and cervical cancer samples. Currently, CIN I is considered as a set of low-grade injuries (low-grade squamous intraepithelial lesions, LSIL), while CIN II, CIN III and cancer in situ are considered as high-grade lesions (high-grade squamous intraepithelial lesions, HSIL). A slab was prepared with the 50micron block, which was subsequently cut into 5 microns; later, the same thing was done at two more levels to reevaluate the histopathological diagnosis and correlate it with the initial diagnosis issued by the institution. Results: During the examination of the additional block levels, a difference was observed from the initial diagnosis: of 32 cases of HPV diagnosis, there were 17 changes to CIN I; of 31 cases of CIN I, there were 4 changes to CIN II; of 30 cases of CIN II, there were 8 changes to CIN III and 1 change to invasive cancer; of 29 cases of CIN III, there were 9 changes to cancer in situ; and finally, of 14 cases of cancer in situ, there was 1 change to invasive cancer. After the statistical analysis, a value of p <0.05 was obtained, which indicated that the differences were statistically significant. Conclusion: By modifying the histopathological study technique, guidelines can be given to generate a more accurate diagnosis with a more solid base, and thus, a more appropriate and timely treatment can be offered to avoid the development of cervical cancer.
The aim of this study was to estimate the territory at risk of establishment of influenza type A (EOITA) in Mexico, using geospatial models. A spatial database of 1973 outbreaks of influenza worldwide was used to develop risk models accounting for natural (natural threat), anthropic (man-made) and environmental (combination of the above) transmission. Then, a virus establishment risk model; an introduction model of influenza A developed in another study; and the three models mentioned were utilized using multi-criteria spatial evaluation supported by geographically weighted regression (GWR), receiver operating characteristic analysis and Moran’s I. The results show that environmental risk was concentrated along the Gulf and Pacific coasts, the Yucatan Peninsula and southern Baja California. The identified risk for EOITA in Mexico were: 15.6% and 4.8%, by natural and anthropic risk, respectively, while 18.5% presented simultaneous environmental, natural and anthropic risk. Overall, 28.1% of localities in Mexico presented a High/High risk for the establishment of influenza type A (area under the curve=0.923, P<0.001; GWR, r2=0.840, P<0.001; Moran’s I =0.79, P<0.001). Hence, these geospatial models were able to robustly estimate those areas susceptible to EOITA, where the results obtained show the relation between the geographical area and the different effects on health. The information obtained should help devising and directing strategies leading to efficient prevention and sound administration of both human and financial resources.
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