Business plan: Step

This project has the goal of creating a business plan to verify the economic viability of the creation of a blockchain-based social media platform that helps users to combat procrastination on diverse activities. Procrastination has been a part of human existence for centuries and it happens mainly because we want to avoid negative moods. With the emergence of new technologies, a case can be made that this phenomenon has increased as we have millions of contents to choose from, that we can access in a very easy way, as all we have to do is reach in our pockets and unlock our smartphones. Decision paralysis, no social pressure, uncertainty of what to do are just some of the reasons that lead us to procrastinate. Step will be the social media platform that contributes to its user’s awareness of long-term procrastination effects and that helps them tackle it using positive reinforcement methods such as a token economy. In this paper, you will find: A thorough research of the literature on these topics; An explanation of the method used to validate the business idea; A contextual analysis to the companies’ environment and its industry; A brief explanation of how the social media platform will be structured and on its business model; An internal and competitive analysis; An implementation plan on Marketing and Operations. To finalize, a financial analysis will be done to check the viability of the project within its first 5 years of activity.Este projeto tem o objetivo de criar um plano de negócios para verificar a viabilidade econômica da criação de uma rede social baseada em blockchain que ajude os seus usuários a combater a procrastinação em diversas atividades. A procrastinação tem feito parte da existência humana há séculos e acontece principalmente porque queremos evitar humores negativos. Com o surgimento de novas tecnologias, pode-se comprovar que este fenômeno se intensificou, pois temos milhões de conteúdos à sua escolha, aos quais podemos aceder de uma forma muito fácil, pois basta desbloquear os nossos smartphones. Paralisia de decisão, ausência de pressão social e incerteza do que fazer são apenas alguns dos motivos que nos levam a procrastinar. A Step será uma rede social que contribui para a consciencialização do usuário sobre os efeitos da procrastinação de longo prazo e que os ajuda a enfrentá-la usando métodos de reforço positivo, como a economia de tokens. Neste artigo, irá encontrar: Uma pesquisa completa da literatura sobre todos estes diferentes tópicos; Uma explicação do método usado para validar a ideia de negócio; Uma análise contextual do ambiente da empresa e da sua indústria; Uma breve explicação de como a rede social será estruturada e o seu modelo de negócios; Uma análise interna e competitiva; Um plano de implementação em Marketing e Operações e, para finalizar, será feita uma análise financeira para verificar a viabilidade do projeto nos primeiros 5 anos de atividade

The effect of pungent and tingling compounds from Piper nigrum\textit {Piper nigrum} L. on background K+K^{+} currents

Black peppercorns ($\textit {Piper nigrum}$ L.) elicit a pungent and tingling oral impression. Their pungency is partially explained by the agonist activity of some of their active principles, especially piperine, on TRP channels. However, we recently showed that piperine, as well as other pungent compounds, also possess a marked effect on two-pore domain (KCNK, $K_{2P}$) $K^{+}$ channels. Members of this family play a key role in maintaining the resting membrane potential of excitable cells. Interestingly, tingling compounds have been shown to induce neuronal excitation by inhibiting KCNK channels. We addressed the question of whether it was plausible that KCNK channels could constitute a physiologically relevant target for the sensory active compounds present in black peppercorns. Because previous studies have demonstrated that mouse trigeminal neurons respond to several pungent compounds, to which humans are also sensitive, we used a primary culture of mouse trigeminal neurons to investigate whether the effect of piperine on these cell types could also be mediated by KCNK channels. We observed that even in the presence of classical TRP-antagonists, piperine was still able to activate a fraction of trigeminal neurons. Furthermore, our results showed that piperine is capable of inducing neuronal depolarization by a mechanism that does not require extracellular $Na^{+}$ or $Ca^{2+}$. This depolarization was mediated by the inhibition of a background $K^{+}$ conductance, most likely corresponding to the KCNK channels of the TASK subfamily. We then performed a screening with 12 other pungent and/or tingling chemosensates isolated from black peppercorns. These compounds were evaluated on Xenopus laevis oocytes expressing the human orthologues of KCNK3, KNCK9 and KCNK18, which we previously showed to be inhibited by piperine. Remarkably, almost all of the isolated chemosensates inhibited the basal activity of hKCNK3, with 1-(octadeca-$\textit {2E,4E,13/12Z}$-trienoyl) pyrrolidine acting as one of the most potent natural blockers for hKCNK3 found to date. Our results suggest that KCNK channels, especially KCNK3, are likely to play a complementary role to TRP channels in the complex orosensory impression elicited by black peppercorns, while they also help to expand the pharmacological knowledge of KCNK channels

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease