Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

The influence of physical fatigue on telephone-based neuropsychological test performance in COVID-19 survivors.

Fatigue has been characterized as a post COVID-19 condition known to persist months after SARS-CoV-2 infection. COVID-19 has been reported to be associated with impaired cognitive function, including disorders in attention, memory, information processing, and executive functions. The objective of this study was to determine if post-COVID fatigue, manifested as tiredness while performing low-intensity physical activity, has a detrimental effect on neuropsychological performance, to achieve this, we randomly selected 20 participants with post-COVID fatigue and 20 SARS-CoV-2 negative age-matched controls from a database of 360 residents of Tijuana, Baja California in a cross-sectional study design. All 40 participants responded to a health survey, along with a neuropsychological assessment test via telephone call. Statistical analysis was performed using a multiple linear regression model including the following independent variables: study condition (post-COVID fatigue or negative control), sex, age, years of education, hypertension, asthma, administration of supplemental oxygen during COVID-19 recovery, and the hour at which the evaluation started. Significant regression analysis was obtained for all global parameters of the assessment, including BANFE-2 score (p = 0.021, R2 Adj. = 0.263), NEUROPSI score (p = 0.008, R2 Adj. = 0.319), and total errors (p = 0.021, R2 Adj. = 0.263), with significant regression coefficients for study condition on two global parameters, BANFE-2 score (p = 0.028, ß = - 0.371) and NEUROPSI score (p = 0.010, ß = -0.428). These findings suggest that the presence of post-COVID fatigue is a factor associated with a decrease in neuropsychological performance.

Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae).

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL-1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 µg mL-1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.

Differential proteins among normal cervix cells and cervical cancer cells with HPV-16 infection, through mass spectrometry-based Proteomics (2D-DIGE) in women from Southern México.

BACKGROUND: Cervical cancer (CC) is the fourth most common cancer in women worldwide with an estimated 528,000 new cases in 2012. The same year México had an incidence of 13,960 and a mortality of 4769 cases. There are several diagnosis methods of CC; among the most frequents are the conventional Pap cytology (Pap), colposcopy, and visual inspection with acetic acid (VIA), histopathological examination, tests of imaging and detection of high-risk papilloma virus (HR-HPV) with molecular tests (PCR, hybridization, sequencing). Proteomics is a tool for the detection of new biomarkers that can be associated with clinical stage, histological type, prognosis, and/or response to treatment. In this study we performed a comparative analysis of CC cells with normal cervical cells. The proteomic analysis was carried out with the fluorescent two-dimensional electrophoresis (2D-DIGE) technique to subsequently identify differential protein profiles using Decyder Software, and the selected proteins were identified by Mass Spectrometry (MALDI-TOF). RESULTS: The proteins that showed an increased expression in cervical cancer in comparison with normal cervix cells were: Mimecan, Actin from aortic smooth muscle and Lumican. While Keratin, type II cytoskeletal 5, Peroxiredoxin-1 and 14-3-3 protein sigma showed a decrease in their protein expression level in cervical cancer in comparison with normal cervix cells. CONCLUSIONS: Thus, this study was successful in identifying biomarker signatures for cervical cancer, and might provide new insights into the mechanism of CC progression.

Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens.

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren's syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.

Spanish Translation and Cultural Adaptation of the Intensive Care Unit Delirium Playbook.

Background: A lack of high-quality provider education hinders the delivery of standard-of-care delirium detection and prevention practices in the intensive care unit (ICU). To fill this gap, we developed and validated an e-learning ICU Delirium Playbook consisting of eight videos and a 44-question knowledge assessment quiz. Given the increasing Spanish-speaking population worldwide, we translated and cross-culturally adapted the playbook from English into Spanish. Objective: To translate and culturally adapt the ICU Delirium Playbook into Spanish, the second most common native language worldwide. Methods: The translation and cross-cultural adaptation process included double forward and back translations and harmonization by a 14-person interdisciplinary team of ICU nurses and physicians, delirium experts, methodologists, medical interpreters, and bilingual professionals representing many Spanish-speaking global regions. After a preeducation quiz, a nurse focus group completed the playbook videos and posteducation quiz, followed by a semistructured interview. Results: The ICU Delirium Playbook: Spanish Version maintained conceptual equivalence to the English version. Focus group participants posted mean (standard deviation) pre- and post-playbook scores of 63% (10%) and 78% (12%), with a 15% (11%) pre-post improvement (P = 0.01). Participants reported improved perceived competency in performing the Confusion Assessment Method for the ICU and provided positive feedback regarding the playbook. Conclusion: After translation and cultural adaptation, the ICU Delirium Playbook: Spanish Version yielded significant knowledge assessment improvements and positive feedback. The Spanish playbook is now available for public dissemination.

Emerging avenues linking myeloid-derived suppressor cells to periodontal disease.

Periodontal disease is one of the most common inflammatory disorders in humans. Gingivitis is the mildest form of periodontal disease and its progression can lead to periodontitis, an inflammatory disease characterized by soft tissue damage that can lead to progressive destruction of the periodontal ligament and alveolar bone. Diverse populations of immune cells are involved in periodontal disease. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous group of immature myeloid cells derived from hematopoietic precursor cells and exhibit T cell immunosuppressive functions that are thought to be involved in periodontal disease. Therefore, MDSCs have been recently analyzed in the context of this disease. In this review, we discuss the most recent advances in the characterization of the biological aspects, subpopulations, and traffic of MDSCs, as well as their immunosuppressive and osteoclastogenic activity in the context of periodontal disease and in the presence of key periodontal pathogens.

Prevalence of SARS-CoV-2 infection in Baja California, Mexico: Findings from a community-based survey in February 2021 in the Mexico-United States border.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics.

Long Non-coding RNAs: Regulators of the Activity of Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.

Epigenetic mechanisms in odontogenic tumors: A literature review.

OBJECTIVE: Epigenetic mechanisms, such as DNA methylation, regulate important biological processes as gene expression and it was suggested that these phenomena play important roles in the carcinogenesis and tumor biology. The aim of this review is to provide the current state of knowledge about epigenetic alterations, focusing mainly on DNA methylation, reported in odontogenic tumors. DESIGN: Literatures were searched based in the combination of the following keywords: odontogenic tumors, epigenetics, DNA methylation, histone modifications, non-coding RNA, microRNA, DNA methyltransferases. Electronic databases (Medline/PubMed, Scopus and Web of Science) were screened. RESULTS: The analysis of epigenetic alterations in different tumors has rapidly increased; however, limited information is available about epigenetic mechanisms involved in the formation of odontogenic tumors. DNA methylation is the most studied epigenetic modification in these tumors and the participation of non-coding RNA's in odontogenic tumors has been recently addressed. Differential expression of DNA methyltransferases, altered DNA methylation patterns and aberrant expression of non-coding RNA's were reported in odontogenic tumors. CONCLUSIONS: Current studies suggest epigenetics as an emerging mechanism, possibly implicated in etiopathogenesis of odontogenic tumors. Deeper understanding of the epigenetic abnormalities in these tumors could show potential applications as biomarkers or therapeutic possibilities in the future.

Low Proteolytic Clipping of Histone H3 in Cervical Cancer.

Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes. Recently, a potential mechanism, which regulates gene expression at transcriptional levels is the proteolytic clipping of histone H3. However, until now this process in CC has not been reported. Using HeLa cells as a model of CC and human samples from patients with CC, we identify that the H3 cleavage was lower in CC compared with control tissue. Additionally, the histone H3 clipping was performed by serine and aspartyl proteases in HeLa cells. These results suggest that histone H3 clipping operates as part of post-translational modification system in CC.