PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.

High-risk human papillomaviruses (HR-HPVs) are the causal agents of cervical, anogenital and a subset of head and neck carcinomas (HNCs). Indeed, oropharyngeal cancers are a type of HNC highly associated with HR-HPV infections and constitute a specific clinical entity. The oncogenic mechanism of HR-HPV involves E6/E7 oncoprotein overexpression for promoting cell immortalization and transformation, through the downregulation of p53 and pRB tumor suppressor proteins, among other cellular targets. Additionally, E6/E7 proteins are involved in promoting PI3K/AKT/mTOR signaling pathway alterations. In this review, we address the relationship between HR-HPV and PI3K/AKT/mTOR signaling pathway activation in HNC with an emphasis on its therapeutic importance.

Medical education and mental health during COVID-19: a survey across 9 countries.

OBJECTIVES: To investigate students' experience with medical education alongside their mental and physical health since the onset of the COVID-19 pandemic across nine countries. METHODS: A cross-sectional online survey was distributed by local collaborators to 2,280 medical students across 148 medical schools in Brazil, Chile, Colombia, Germany, Italy, Japan, Mexico, Spain, and Venezuela using non-probability convenience sampling from June 22 to July 24, 2020. Students answered questions regarding teaching, internet use, COVID-19, physical and mental well-being. A multivariate logistic regression examined factors associated with depressed mood, insomnia, and headache. RESULTS: Academic teaching shifted to a virtual (67%, n=1,534) or hybrid environment (23%, n=531), whilst bedside teaching was suspended or cancelled (93%, n=2,120). Across all countries students were equally satisfied with the teaching modality, quantity, quality, and the evaluation system of in-person, hybrid, and online curricula. Negative changes in mental (40% (n=912) insomnia, 57% (n=1,300) emotional irritability, 47% (n=1,072) emotional instability, 41% (n=935) anhedonia, 40% (n=912) depressed mood) and physical (36% (n=821) headache, 57% (n=1,299) ocular tiredness, 49% (n=1,117) backache) health symptoms were frequently observed. Positive associations between the number of daily screen hours and depressed mood (adjusted odds ratio (AOR)=1.09, 95%CI: 1.05-1.12, p<.001), insomnia (AOR=1.08, 95%CI: 1.05-1.11, p<.001), and headache (AOR=1.11, 95%CI: 1.07-1.14, p<.001) were identified. CONCLUSIONS: Students' experience with digital and hybrid medical curricula was diverse during the pandemic. Education modality, quantity, and quality were positively evaluated. However, students' mental and physical health worsened. Besides bedside teaching, faculties ought to digitalize and strengthen social communities and extend support services for students.

Lifestyle Changes Among Medical Students During COVID-19 Pandemic: A Multicenter Study Across Nine Countries.

The global pandemic caused by coronavirus disease-2019 (COVID-19) disrupted both public and private life for many. Concerning medical students, practical teaching and classrooms were substituted with a virtual curriculum. However, how this new academic environment has affected students' health and lifestyles has yet to be studied. In this study, we surveyed 2,776 students from nine different countries about changes in their university curricula and potential alterations in their daily habits, physical health, and psychological status. We found negative changes across all countries studied, in multiple categories. We found that 99% of respondents indicated changes in their instruction delivery system, with 90% stating a transition to online education, and 93% stating a reduction or suspension of their practical activities. On average, students spent 8.7 hours a day in front of a screen, with significant differences among countries. Students reported worsened studying, sleeping, and eating habits with substantial differences in Latin American countries. Finally, the participants frequently expressed onset and increase in both mental and physical health symptoms: backache, asthenopia, irritability, and emotional instability. Altogether, these results suggest a potential risk in the health and academic performance of future doctors if these new academic modalities are maintained.

Role of Pirin, an Oxidative Stress Sensor Protein, in Epithelial Carcinogenesis.

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains a novel area of study. This review presents accumulating evidence on the contribution of Pirin in epithelial cancers, involved signaling pathways, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis.

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

Comparison of intradialytic versus home-based exercise programs on physical functioning, physical activity level, adherence, and health-related quality of life: pilot study.

Intradialytic exercise (ID) programs are effective and safe for hemodialysis (HD) patients to avoid functional deterioration. However, exercise is not routinely undertaken in most HD units, and we do not know if home-based (HB) programs are as effective as ID programs. The purpose of this study was to compare the effects of 16 weeks of ID exercise versus a HB exercise program for HD patients. A total of 46 patients were randomly assigned to the ID group (n = 24) or HB group (n = 22). They completed a 16-week combined exercise program 3 times/week. We measured physical activity level, physical functioning, depression level, and health-related quality of life at baseline and after 16 weeks. A significant time effect was found in both groups for the physical activity level (p = 0.012). There was also a significant group-time interaction effect for the one-leg standing test (OLST) (p = 0.049) and a significant time effect for the Short Physical Performance Battery (p = 0.013), timed up-and-go test (p = 0.005), sit-to-stand-10 (p = 0.027), right and left hand handgrip (p = 0.044, p < 0.001), one-heel left leg raise (p = 0.019), and 6-minute walking (p = 0.006), depression (p = 0.017). HRQoL remained unchanged. There was no difference between the two interventions on the tested outcomes (besides OLST). Both interventions were associated with positive changes of the physical activity levels and physical function.

Gestión de las bajas laborales / Management of sick leaves

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