Validation of the Spanish version of the Pediatric Asthma Severity Score (PASS) in a population of Hispanic children.

BACKGROUND: The Pediatric Asthma Severity Score (PASS) is one of the most-used clinical scoring systems for assessing the severity of asthma exacerbations in children. The aim of the present study was to validate a Spanish version of the PASS in a population of Hispanic children with asthma exacerbations living in urban Bogota, Colombia. METHODS: In a prospective cohort and a validation study, parents/caregivers of children between 2 and 18 years old attended in the emergency department (ED) with asthma exacerbations who were admitted to the inpatient unit were invited to participate in the study. During the hospitalization period, we gathered the necessary data for assessing the criterion validity (comparing its score with the Pediatric Respiratory Assessment Measure [PRAM]), construct validity, interrater reliability, responsiveness, and internal consistency of the Col-PASS, the Colombian version of the PASS. RESULTS: At baseline, the scores of the Col-PASS correlated positively with the scores of the PRAM score (ρ = 0.588, p < .001). The baseline Col-PASS scores in patients who required admission to a more complex service were significantly higher than those in patients who presented clinical improvement (1.0 (0.0-2.0) vs. 0.0 (0.0-0.0), p < .001). The interrater reliability was found to be κ = 0.897, 95% CI 0.699-1.000, p < .001. Cronbach's α was .701 for the questionnaire as a whole. CONCLUSION: The Col-PASS has excellent construct validity, adequate criterion validity, interrater reliability, responsiveness; and acceptable internal consistency when used in children between 2 and 18 years old with asthma exacerbations.

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV's ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.

Effectiveness of ultrasonic activation over glycolic acid on microhardness, cohesive strength, flexural strength, and fracture resistance of the root dentin.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of ultrasonic activation (US) over glycolic acid on microhardness, cohesive strength, flexural strength, and fracture resistance of root dentin, comparing with conventional final irrigation protocols. METHODS: Samples were obtained from 140 extracted bovine teeth and distributed into four test groups: microhardness (50 teeth), cohesive strength (15 teeth), flexural strength (15 teeth), and fracture resistance (60 teeth). In all four tests, specimens were subdivided into five groups, according to final irrigation protocols: G1: distilled water (DW); G2: 17% ethylenediaminetetraacetic acid (EDTA); G3: 17% glycolic acid (GA); G4: 17% EDTA + US; and G5: 17% GA + US. The duration time of each protocol was set in 1 min. After irrigation protocols, the Vickers tester was used to evaluate microhardness and the universal testing machine was used to evaluate the cohesive strength, flexural strength, and fracture resistance of the root dentin. One-way ANOVA test and the Tukey HSD were used for multiple comparison tests in all evaluations (α = 5%). RESULTS: In general, groups 2 (EDTA), 4 (EDTA + US), and 5 (GA + US) promoted the highest reduction of microhardness, being statistically different from other groups (p < 0.05). Cohesive strength, flexural strength, and fracture resistance data revealed that no differences between groups were observed (p > 0.05). CONCLUSIONS: The association of GA and US results in microhardness reduction, with no influence on cohesive strength, flexural strength, and fracture resistance of the root dentin. CLINICAL RELEVANCE: The use of US over GA has no influence on some mechanical properties of root dentin.

pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation.

The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.

PLCγ1/PKCθ Downstream Signaling Controls Cutaneous T-Cell Lymphoma Development and Progression.

Developing mechanistic rationales can improve the clinical management of cutaneous T-cell lymphomas. There is considerable genetic and biological evidence of a malignant network of signaling mechanisms, highly influenced by deregulated TCR/PLCγ1 activity, controlling the biology of these lesions. In addition, activated signal transducer and activator of transcription 3 is associated with clinical progression, although the alterations responsible for this have not been fully elucidated. Here, we studied PLCγ1-dependent mechanisms that can mediate STAT3 activation and control tumor growth and progression. Downstream of PLCγ1, the pharmacological inhibition and genetic knockdown of protein kinase C theta (PKCθ) inhibited signal transducer and activator of transcription 3 activation, impaired proliferation, and promoted apoptosis in cutaneous T-cell lymphoma cells. A PKCθ-dependent transcriptome in mycosis fungoides/Sézary syndrome cells revealed potential effector genes controlling cytokine signaling, TP53, and actin cytoskeleton dynamics. Consistently, an in vivo chicken embryo model xenografted with mycosis fungoides cells showed that PKCθ blockage abrogates tumor growth and spread to distant organs. Finally, the expression of a number of PKCθ target genes found in mycosis fungoides cells significantly correlated with that of PRKCQ (PKCθ) in 81 human mycosis fungoides samples. In summary, PKCθ can play a central role in the activation of malignant cutaneous T-cell lymphoma mechanisms via multiple routes, including, but not restricted to, STAT3. These mechanisms may, in turn, serve as targets for specific therapies.

ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer.

The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. In the last decade, several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown. In this study, we performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure. In addition, we studied at the protein level the expression of these genes in cancer samples and performed functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development. Remarkably, we found that 20% of lung cancer patients show ARID2 protein loss, partially explained by the presence of ARID2 mutations. In addition, we showed that ARID2 deficiency provokes profound chromatin structural changes altering cell transcriptional programs, which bolsters the proliferative and metastatic potential of the cells both in vitro and in vivo. Moreover, we demonstrated that ARID2 deficiency impairs DNA repair, enhancing the sensitivity of the cells to DNA-damaging agents. Our findings support that ARID2 is a bona fide tumor suppressor gene in lung cancer that may be exploited therapeutically.

Eficácia de agentes químicos na desinfecção de tubetes anestésicos odontológicos / Effectiveness of chemical agents in disinfecting dental anesthetic cartridges

Durante o atendimento odontológico, o paciente pode ser exposto a várias fontes de contaminações, por isso a equipe odontológica deve sempre implementar ações de biossegurança. Materiais não autoclaváveis, como os tubetes anestésicos, necessitam ser desinfetados previamente ao seu uso, pois não são estéreis, podendo transmitir patógenos entre os pacientes. Este estudo objetivou avaliar e comparar a eficácia de três soluções desinfetantes na redução da carga microbiana em tubetes de anestésicos odontológicos. Os tubetes anestésicos (n = 31) foram escolhidos aleato-riamente e submetidos a diferentes métodos e agentes desinfetantes (Álcool 70%, Dióxido de Cloro 7%; Cloreto de benzalcônio 5,2% com Polihexametileno biguanida 3,5%). Após a desinfecção por métodos de imersão ou fricção, os tubetes foram semeados em meio de cultura contendo caldo tripticase de soja e incubados (48h/37 ºC). Amostras do meio de cultura líquido foram repicadas e semeadas em ágar tripticase de soja, incubado durante 48h a 37 ºC. O crescimento microbiano foi observado pela presença de unidades formadoras de colônias (UFCs) crescidas no ágar. O estudo concluiu que os produtos Álcool 70% e Cloreto de benzalcônio 5,2% com Polihexametileno biguanida 3,5% demostraram ser mais eficazes na eliminação da carga microbiana dos tubetes pelo método de fricção, e que realmente os tubetes anestésicos tem sua superfície externa contaminada. O estudo comprovou ser o método de fricção do agente desinfetante mais eficaz na redução da carga microbiana comparado a imersão. Dos agentes testados, o Dióxido de Cloro 7% não demonstrou um nível de desinfecção satisfatório.

During dental care, the patient may be exposed to various sources of contamination, so the dental team should always implement biosecurity actions. Non-autoclavable materials such as anesthetic cartridges need to be di-sinfected prior to use because they are not sterile and can transmit pathogens between patients. This study aimed to evaluate and compare the effectiveness of three disinfectant solutions to reduce microbial load in dental anesthetic cartridges. Anesthetic cartridges (n = 31) were randomly chosen and submitted to different methods and disinfectants (70% Alcohol, 7% Chlorine Dioxide; 5.2% Benzalkonium Chloride with 3.5% Polyhexamethylene Biguanide). After immersion or friction methods of disinfection, the tubes were seeded in culture medium containing trypticase soy broth and incubated (48h/37 ºC). Samples of liquid culture medium were picked and seeded in trypticase soy agar, incubated for 48h at 37 ºC. Microbial growth was observed by the number of colonies forming units (CFUs) grown on the agar. The study concluded that 70% Alcohol and 5.2% Benzalko-nium Chloride with 3.5% Polyhexamethylene biguanide have been shown to be most effective in eliminating the microbial contamination of the cartridges by the friction method, and that the anesthetic cartridges actually have contamination of their external surface. The study proved that the friction method is most effective in reducing microbial load compared to immersion. Of the agents tested, 7% Chlorine Dioxide did not show a satisfactory level of disinfection.

Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies.

Effective cancer treatment has been precluded by the presence of various forms of intratumoral complexity that drive treatment resistance and metastasis. Recent single-cell sequencing technologies are significantly facilitating the characterization of tumor internal architecture during disease progression. New applications and advances occurring at a fast pace predict an imminent broad application of these technologies in many research areas. As occurred with next-generation sequencing (NGS) technologies, once applied to clinical samples across tumor types, single-cell sequencing technologies could trigger an exponential increase in knowledge of the molecular pathways involved in cancer progression and contribute to the improvement of cancer treatment.