Cancer immunotherapy: A comprehensive appraisal of its modes of application.

peer reviewedConventional cancer treatments such as chemotherapy and radiation therapy have reached their therapeutic potential, leaving a gap for developing more effective cancer therapeutics. Cancer cells evade the immune system using various mechanisms of immune tolerance, underlying the potential impact of immunotherapy in the treatment of cancer. Immunotherapy includes several approaches such as activating the immune system in a cytokine-dependent manner, manipulating the feedback mechanisms involved in the immune response, enhancing the immune response via lymphocyte expansion and using cancer vaccines to elicit long-lasting, robust responses. These techniques can be used as monotherapies or combination therapies. The present review describes the immune-based mechanisms involved in tumor cell proliferation and maintenance and the rationale underlying various treatment methods. In addition, the present review provides insight into the potential of immunotherapy used alone or in combination with various types of therapeutics

Public health effects of travel-related policies on the COVID-19 pandemic: A mixed-methods systematic review

Objectives: To map travel policies implemented due to COVID-19 during 2020, and conduct a mixed methods systematic review of health effects of such policies, and related contextual factors. Design: Policy mapping and systematic review. Data sources and Eligibility Criteria: for the policy mapping, we searched websites of relevant government bodies and used data from the Oxford COVID-19 Government Response Tracker for a convenient sample of 31 countries across different regions. For the systematic review, we searched Medline (Ovid), PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and COVID-19 specific databases. We included randomized controlled trial, non-randomized studies, modeling studies, and qualitative studies. Two independent reviewers selected studies, abstracted data and assessed risk of bias. Results: Most countries adopted a total border closure at the start of the pandemic. For the remainder of the year, partial border closure banning arrivals from some countries or regions was the most widely adopted measure, followed by mandatory quarantine and screening of travelers. The systematic search identified 69 eligible studies, including 50 modeling studies. Both observational and modeling evidence suggest that border closure may reduce the number of COVID-19 cases, disease spread across countries and between regions, and slow the progression of the outbreak. These effects are likely to be enhanced when implemented early, and when combined with measures reducing transmission rates in the community. Quarantine of travelers may decrease the number of COVID-19 cases but its effectiveness depends on compliance and enforcement and is more effective if followed by testing, especially when less than 14 day-quarantine is considered. Screening at departure and/or arrival is unlikely to detect a large proportion of cases or to delay an outbreak. Effectiveness of screening may be improved with increased sensitivity of screening tests, awareness of travelers, asymptomatic screening, and exit screening at country source. While four studies on contextual evidence found that the majority of the public is supportive of travel restrictions, they uncovered concerns about the unintended harms of those policies.Peer Reviewe

The Role of Rho GTPases in VEGF Signaling in Cancer Cells

Vascular endothelial growth factors (VEGFs) consist of five molecules (VEGFA through D as well as placental growth factor) which are crucial for regulating key cellular and tissue functions. The role of VEGF and its intracellular signaling and downstream molecular pathways have been thoroughly studied. Activation of VEGF signal transduction can be initiated by the molecules’ binding to two classes of transmembrane receptors: (1) the VEGF tyrosine kinase receptors (VEGF receptors 1 through 3) and (2) the neuropilins (NRP1 and 2). The involvement of Rho GTPases in modulating VEGFA signaling in both cancer cells and endothelial cells has also been well established. Additionally, different isoforms of Rho GTPases, namely, RhoA, RhoC, and RhoG, have been shown to regulate VEGF expression as well as blood vessel formation. This review article will explore how Rho GTPases modulate VEGF signaling and the consequences of such interaction on cancer progression

Nondepolarizing muscle relaxant improves direct laryngoscopy view with no effect on face mask ventilation

Background: Difficult or impossible face mask ventilation complicated with difficult tracheal intubation during anesthesia induction occurs in 0.4% of adult anesthesia cases, possibly leading to life-threatening complications. Because of such catastrophes, muscle relaxants have been recommended to be administered after confirming adequate face mask ventilation without a solid scientific validation of this principal. Methods: In this observational study, the ease of ventilation and the scores of direct laryngoscopy views before and after administration of cisatracurium were assessed in ninety young healthy adults, without anesthetic risks and without foreseen difficult intubation and who were scheduled for general elective surgeries. Results: Before muscle relaxation, 43 patients (48%) were Cormack Grade I, while the remaining 47 patients (52%) were either Cormack Grade II (28 patients, 31%) or Cormack Grade II (19 patients, 21%). Following muscle relaxation with cisatracurium, the number of patients with Cormack Grade I significantly increased from 43 patients (48%) to 65 patients (72%) (p = 0.0013). Only 1 patient out of 19 patients (5%) improved his Cormack grade from Grade III to Grade I while 16 out 19 patients (84%) improved their Cormack grade from Grade III to Grade II after the use of cisatracurium. The quality of face mask ventilation did not differ with and without muscle relaxants in all patients. Conclusion: The use of cisatracurium in healthy young adults undergoing general elective surgeries with no anticipated difficult endotracheal intubation had no effect on the quality of face mask ventilation despite resulting in a quantifiable improvement in the laryngeal view. Resumo: Justificativa: A ventilação difícil ou impossível via máscara facial complicada pela intubação traqueal difícil durante a indução da anestesia ocorre em 0,4% dos casos de anestesia em adultos, possivelmente levando a complicações fatais. Devido a tais catástrofes, recomendou-se que a administração de relaxantes musculares seja feita após a confirmação de ventilação adequada via máscara facial, sem uma validação científica sólida dessa conduta. Métodos: Neste estudo observacional, a facilidade de ventilação e os escores de visibilidade em laringoscopia direta antes e após a administração de cisatracúrio foram avaliados em 90 adultos jovens e saudáveis, sem riscos anestésicos e sem intubação difícil prevista, agendados para cirurgias eletivas gerais. Resultados: Antes do relaxamento muscular, 43 pacientes (48%) eram Cormack Grau I, enquanto os 47 pacientes (52%) restantes eram ou Cormack Grau II (28 pacientes, 31%) ou Cormack Grade III (19 pacientes, 21%). Após o relaxamento muscular com cisatracúrio, o número de pacientes com Cormack Grau I aumentou significativamente de 43 (48%) para 65 pacientes (72%) (p = 0,0013). Apenas um paciente (5%) dos 19 melhorou sua classificação de Cormack do Grau III para o Grau I, enquanto 16 dos 19 pacientes (84%) melhoraram suas classificações de Cormack do Grau III para o grau II após o uso de cisatracúrio. A qualidade da ventilação via máscara facial não diferiu com ou sem relaxantes musculares em todos os pacientes. Conclusão: O uso de cisatracúrio em adultos jovens saudáveis submetidos a cirurgias eletivas gerais sem intubação traqueal difícil prevista não teve efeito sobre a qualidade da ventilação via máscara facial, mesmo resultando em melhora quantificável da visibilidade da laringe. Keywords: Nondepolarizing muscle relaxants, Laryngoscopy view, Face mask ventilation, Palavras-chave: Relaxantes musculares não despolarizantes, Visibilidade em laringoscopia, Ventilação via máscara facia

Nondepolarizing muscle relaxant improves direct laryngoscopy view with no effect on face mask ventilation

Abstract Background: Difficult or impossible face mask ventilation complicated with difficult tracheal intubation during anesthesia induction occurs in 0.4% of adult anesthesia cases, possibly leading to life-threatening complications. Because of such catastrophes, muscle relaxants have been recommended to be administered after confirming adequate face mask ventilation without a solid scientific validation of this principal. Methods: In this observational study, the ease of ventilation and the scores of direct laryngoscopy views before and after administration of cisatracurium were assessed in ninety young healthy adults, without anesthetic risks and without foreseen difficult intubation and who were scheduled for general elective surgeries. Results: Before muscle relaxation, 43 patients (48%) were Cormack Grade I, while the remaining 47 patients (52%) were either Cormack Grade II (28 patients, 31%) or Cormack Grade II (19 patients, 21%). Following muscle relaxation with cisatracurium, the number of patients with Cormack Grade I significantly increased from 43 patients (48%) to 65 patients (72%) (p = 0.0013). Only 1 patient out of 19 patients (5%) improved his Cormack grade from Grade III to Grade I while 16 out 19 patients (84%) improved their Cormack grade from Grade III to Grade II after the use of cisatracurium. The quality of face mask ventilation did not differ with and without muscle relaxants in all patients. Conclusion: The use of cisatracurium in healthy young adults undergoing general elective surgeries with no anticipated difficult endotracheal intubation had no effect on the quality of face mask ventilation despite resulting in a quantifiable improvement in the laryngeal view