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COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.LifeArc and CW+.

Restaurant management requires customer responsiveness to deal with increasingly higher expectations and market competitiveness. This study proposes an approach to simplify the decision-making process of restaurant managers by combining both live social media customer feedback and historical sales data in a sales forecast model (based on TripAdvisor data and the Bass model). Our approach was validated with internal and external (i.e., online reviews) data gathered from six restaurants. The collected data was processed using data analytics for developing a dashboard that provides value for restauranteurs by taking advantage of online reviews and sales forecast. Such dashboard was evaluated by restaurant management experts, which provided positive feedback, highlighting in particular the time saved in the decision-making process. info:eu-repo/semantics/acceptedVersion

Summary Background The tight control of cell proliferation and cell death is essential to normal tissue development, and the loss of this control is a hallmark of cancers. Cell growth and cell death are coordinately regulated during development by the Hippo signaling pathway. The Hippo pathway consists of the Ste20 family kinase Hippo, the WW adaptor protein Salvador, and the NDR kinase Warts. Loss of Hippo signaling in Drosophila leads to enhanced cell proliferation and decreased apoptosis, resulting in massive tissue overgrowth through increased expression of targets such as Cyclin E and Diap1. The cytoskeletal proteins Merlin and Expanded colocalize at apical junctions and function redundantly upstream of Hippo. It is not clear how they regulate growth or how they are localized to apical junctions. Results We find that another Drosophila tumor-suppressor gene, the atypical cadherin fat , regulates both cell proliferation and cell death in developing imaginal discs. Loss of fat leads to increased Cyclin E and Diap1 expression, phenocopying loss of Hippo signaling. Ft can regulate Hippo phosphorylation, a measure of its activation, in tissue culture. Importantly, fat is needed for normal localization of Expanded at apical junctions in vivo. Genetic-epistasis experiments place fat with expanded in the Hippo pathway. Conclusions Together, these data suggest that Fat functions as a cell-surface receptor for the Expanded branch of the conserved Hippo growth control pathway.

Behavioral effects of a medial prefrontal cortex (MPFC) transection were assessed in animal tests of anxiety. Social investigation and plus-maze open arm exploration increased in MPFC damaged animals relative to sham ones. MPFC lesions prevented d -amphetamine (2 mg/kg, i.p.) induced social investigation decrease and exaggerated general locomotion increase. Diazepam (1 mg/kg, i.p.) and MPFC synergistically increased open arm exploration on a second (repeated) plus-maze trial. These results suggest that the MPFC would be implicated in a generalized mechanism of warning enabling emission of appropriate responses to anxiogenic stimuli. Although, this lesion did not modify motor activity itself, the pattern of the motor activation induced by amphetamine was altered. The role of the MPFC areas in the behavioral response associated with fear is discussed.

Colorectal distention is a non-invasive stimulus used to study visceral pain processing in the nervous system. In this study, immunocytochemical labeling for the immediate-early gene, c-Fos, was used to map limbic brain structures involved in processing visceral pain. Rats received noxious colorectal distention while loosely restrained or loose restraint without distention (control). The brains were immunostained and the density of Fos-labeled nuclei within areas of the brain associated with limbic function were examined. Many cortical (cingulate; retrosplenial; insular; perirhinal, entorhinal) and subcortical (periaqueductal gray; locus coeruleus; lateral parabrachial area; paraventricular, anterodorsal and centromedian thalamic nuclei; lateral septal area; dorsomedial hypothalamus; cortical amygdala; subiculum) areas were labeled in the control rats, but significantly more Fos was observed in these areas following noxious colorectal distention (CRD). Additional areas were labeled following CRD but not restraint (e.g. infralimbic and prelimbic cortices; mediodorsal thalamic nucleus; central amygdaloid nucleus). The results show that noxious visceral stimuli result in Fos expression in limbic structures that exceeds that induced by restraint stress, suggesting that different pathways and circuits are recruited by stimuli which can produce similar emotional responses.

Goldthioglucose (GTG) injected i.p. in mice is known to cause hyperphagia and obesity which is related to ventromedial hypothalamic damage and norepinephrine (NE) depletion in females. In the present experiment 6 doses of GTG were tested in males. After 160 days the monoamine content of whole brain was measured. Norepinephrine (NE) and serotonin (SER) were depleted without changes in dopamine content. Brain NE and SER were both negatively correlated with body weight. These experiments extend earlier studies by suggesting that GTG obesity in mice may be caused by NE depletion in males as well as females and by suggesting that the obesity is also a function of serotonin depletion.