Residual energy use and energy efficiency improvement of European supermarket facilities during the post-COVID and energy crisis period.

Supermarkets are significant consumers of electricity and contribute to the generation of associated pollutant emissions. This will help to mitigate the impact of increased energy costs on the prices of products sold in supermarkets. Therefore, it is essential to reduce energy consumption, starting with the equipment that consumes the most electricity, such as refrigeration, and using the residual thermal energy generated in supermarkets. This paper discusses the impact of rising energy costs in the post-Covid era and during the energy crisis. It evaluates the environmental and energy benefits of implementing energy improvements and utilizing residual energy in real supermarkets. The analysis takes into account the socio-economic characteristics of the EU-27 countries, which affect the economic feasibility of these measures. This would prevent the release of 122 tons of CO2 per year for each supermarket, resulting in energy savings of around 70 % or 305 kWh/m2. The required investments would have a payback period of 4 years.

Frailty in severe COVID-19 survivors after ICU admission. A prospective and multicenter study in Mexico.

OBJECTIVE: To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge. DESIGN: An observational, prospective and multicenter, nation-wide study. SETTING: Eight adult ICU across eight academic acute care hospitals in Mexico. PATIENTS: All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty. RESULTS: 196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio [OR] 3.70, 95% confidence interval 1.40-9.81, P = .008). CONCLUSIONS: Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.

Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

Epilepsy Care in Latin America and the Caribbean: Overcoming Challenges and Embracing Opportunities.

The burden of epilepsy in the Latin America and the Caribbean (LAC) region causes a profound regional impact on the health care system and significantly contributes to the global epilepsy burden. As in many other resource-limited settings worldwide, health care professionals and patients with epilepsy in LAC countries face profound challenges due to a combination of factors, including high disease prevalence, stigmatization of epilepsy, disparities in access to care, limited resources, substantial treatment gaps, insufficient training opportunities for health care providers, and a diverse patient population with varying needs. This article presents an overview of the epidemiology of epilepsy and discusses the principal obstacles to epilepsy care and key contributors to the epilepsy diagnosis and treatment gap in the LAC region. We conclude by highlighting various initiatives across different LAC countries to improve epilepsy care in marginalized communities, listing strategies to mitigate treatment gaps and facilitate better health care access for patients with epilepsy by enhancing the epilepsy workforce.

Relapsing Irritated Seborrheic Keratosis of External Auditory Canal and its Management.

Seborrheic keratosis lesions are tumors that rarely occur in the external auditory canal. There are several histological variants, and one of them is the irritated seborrheic keratosis. This kind has been scarcely reported in the literature. We report a 62 years old man with this lesion that relapses after monopolar electrocautery, and finally is removed by skin flap dissection.

Vestibular Pathology as Early Finding of Friedreich's Ataxia in a 16 Years Old Woman.

Friedreich's ataxia is degenerative disease frequently starting around puberty and it's characterized by a progressive gait ataxia, limb weakness, apparition of Babinsky sign, loss of deep tendon reflex, dysarthria and skeletal deformities. The development of vestibular pathology is common but not completely understood. A 16 years old woman with early vestibular defects in relation to a latter Friedreich's ataxia diagnosis is reported.

Impact of elevated lipoprotein(a) on coronary artery disease phenotype and severity.

AIMS: A thorough characterization of the relationship between elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) is lacking. This study aimed to quantitatively assess the association of increasing Lp(a) levels and CAD severity in a real-world population. METHODS AND RESULTS: This non-interventional, cross-sectional, LipidCardio study included patients aged ≥21 years undergoing angiography (October 2016-March 2018) at a tertiary cardiology centre, who have at least one Lp(a) measurement. The association between Lp(a) and CAD severity was determined by synergy between PCI with taxus and cardiac surgery (SYNTAX)-I and Gensini scores and angiographic characteristics. Overall, 975 patients (mean age: 69.5 years) were included; 70.1% were male, 97.5% had Caucasian ancestry, and 33.2% had a family history of premature atherosclerotic cardiovascular disease. Median baseline Lp(a) level was 19.3 nmol/L. Patients were stratified by baseline Lp(a): 72.9% had < 65 nmol/L, 21.0% had ≥100 nmol/L, 17.2% had ≥125 nmol/L, and 12.9% had ≥150 nmol/L. Compared with the normal (Lp(a) < 65 nmol/L) group, elevated Lp(a) groups (e.g. ≥ 150 nmol/L) had a higher proportion of patients with prior CAD (48.4% vs. 62.7%; P < 0.01), prior coronary revascularization (39.1% vs. 51.6%; P = 0.01), prior coronary artery bypass graft (6.0% vs. 15.1%; P < 0.01), vessel(s) with lesions (68.5% vs. 81.3%; P = 0.03), diffusely narrowed vessels (10.9% vs. 16.5%; P = 0.01) or chronic total occlusion lesions (14.3% vs. 25.2%; P < 0.01), and higher median SYNTAX-I (3.0 vs. 5.5; P = 0.01) and Gensini (10.0 vs. 16.0; P < 0.01) scores. CONCLUSION: Elevated Lp(a) was associated with a more severe presentation of CAD. Awareness of Lp(a) levels in patients with CAD may have implications in their clinical management.

Patients with coronary artery disease (CAD) suffer with progressive plaque buildup in the walls of coronary blood vessels, which restricts blood flow and may result in serious cardiovascular outcomes such as chest pain (angina) and heart attacks (myocardial infarction). In this study, we assessed whether elevated levels of lipoprotein(a) [Lp(a)­a lipoprotein found in blood] are associated with more severe illness. We observed that elevated Lp(a) was associated with a higher proportion of patients with prior CAD, prior interventions on coronary blood vessels, and more diseased blood vessels. These collectively form what is considered a 'severe' clinical presentation of CAD, meaning a greater likelihood of adverse clinical outcomes.

Retinoblastoma vulnerability to combined de novo and salvage pyrimidine ribonucleotide synthesis pharmacologic blockage.

Retinoblastoma is an eye cancer that commonly affects young children. Despite significant advances, current treatments cause side effects even when administered locally, and patients may still have to undergo enucleation. This is particularly disheartening in cases of bilateral retinoblastoma. Hence, there is an urgent need for novel therapeutic strategies. Inhibitors of the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in the de novo pyrimidine ribonucleotide synthesis pathway, have proven to be effective in preclinical trials against several cancers including pediatric cancers. Here we tested whether blocking pyrimidine ribonucleotide synthesis promotes retinoblastoma cell death. Cultured retinoblastoma cell lines were treated with small molecule inhibitors of DHODH alone or in combination with inhibitors of nucleoside uptake to also block the salvage pathway for pyrimidine ribonucleotide formation. On their own, DHODH inhibitors had a moderate killing effect. However, the combination with nucleoside uptake inhibitors greatly enhanced the effect of DHODH inhibition. In addition, we observed that pyrimidine ribonucleotide synthesis blockage can cause cell death in a p53 mutant retinoblastoma cell line derived from a patient with metastasis. Explaining these results, the analysis of a published patient cohort revealed that loss of chr16q22.2 (containing the DHODH gene) is amongst the most frequent alterations in retinoblastoma and that these tumors often show gains in chromosome regions expressing pyrimidine ribonucleotide salvage factors. Furthermore, these genome alterations associate with malignancy. These results indicate that targeting pyrimidine ribonucleotide synthesis may be an effective therapeutic strategy to consider as a treatment for retinoblastoma.

Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID).

PURPOSE: To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. METHODS: A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement," measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame. RESULTS: Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group. CONCLUSIONS: Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.

What Do You See? Signature Pedagogy in Continuous Electroencephalography Teaching.

PURPOSE: Electroencephalography (EEG) is commonly used in neurology, but there is variability in how neurologists interpret EEGs, potentially from variability in EEG teaching. Little is known about how EEG teaching is done to prepare neurologists for professional practice. METHODS: We interviewed a group of EEG experts to characterize their teaching practices around continuous EEG (cEEG). We used signature pedagogy as a framework to analyze and interpret the data. RESULTS: We identified pervasive and characteristic forms of cEEG teaching. Teaching is based on apprenticeship, relying on "learning by doing" in the context of real-life clinical practice. There are habitual steps that learners take to anchor teaching, which typically occurs during rounds. There is a common language and core knowledge that trainees need to master early in their training. CONCLUSIONS: There are pervasive characteristic forms of cEEG teaching. These findings can help facilitate instructional design and implementation of complementary or enhanced cEEG teaching practices.

Why Competency Frameworks Are Insufficiently Nuanced for Health Equity Teaching and Assessment.

This article suggests how competency-based medical education should robustly integrate health equity by focusing on physicians' responsibilities to (1) know why and how underlying structural mechanisms contribute to health equity and then (2) take action to achieve health equity in their practice. This article first canvasses currently available frameworks for helping trainees cultivate these 2 specific skills of discernment and action. This article then offers strategies for teaching and assessing these skills in specific learning activities.

Mood induction through imitation of full-body movements with different affective intentions.

Theories of human emotion, including some emotion embodiment theories, suggest that our moods and affective states are reflected in the movements of our bodies. We used the reverse process for mood regulation; modulate body movements to regulate mood. Dancing is a type of full-body movement characterized by affective expressivity and, hence, offers the possibility to express different affective states through the same movement sequences. We tested whether the repeated imitation of a dancer performing two simple full-body dance movement sequences with different affective expressivity (happy or sad) could change mood states. Computer-based systems, using avatars as dance models to imitate, offer a series of advantages such as independence from physical contact and location. Therefore, we compared mood induction effects in two conditions: participants were asked to imitate dance movements from one of the two avatars showing: (a) videos of a human dancer model or (b) videos of a robot dancer model. The mood induction was successful for both happy and sad imitations, regardless of condition (human vs. robot avatar dance model). Moreover, the magnitude of happy mood induction and how much participants liked the task predicted work-related motivation after the mood induction. We conclude that mood regulation through dance movements is possible and beneficial in the work context.

Pharmacological and genetic increases in liver NADPH levels ameliorate NASH progression in female mice.

Non-alcoholic steatohepatitis (NASH) is one of the fastest growing liver diseases worldwide, and oxidative stress is one of NASH main key drivers. Nicotinamide adenine dinucleotide phosphate (NADPH) is the ultimate donor of reductive power to a number of antioxidant defences. Here, we explored the potential of increasing NADPH levels to prevent NASH progression. We used nicotinamide riboside (NR) supplementation or a G6PD-tg mouse line harbouring an additional copy of the human G6PD gene. In a NASH mouse model induced by feeding mice a methionine-choline deficient (MCD) diet for three weeks, both tools increased the hepatic levels of NADPH and ameliorated the NASH phenotype induced by the MCD intervention, but only in female mice. Boosting NADPH levels in females increased the liver expression of the antioxidant genes Gsta3, Sod1 and Txnrd1 in NR-treated mice, or of Gsr for G6PD-tg mice. Both strategies significantly reduced hepatic lipid peroxidation. NR-treated female mice showed a reduction of steatosis accompanied by a drop of the hepatic triglyceride levels, that was not observed in G6PD-tg mice. NR-treated mice tended to reduce their lobular inflammation, showed a reduction of the NK cell population and diminished transcription of the damage marker Lcn2. G6PD-tg female mice exhibited a reduction of their lobular inflammation and hepatocyte ballooning induced by the MCD diet, that was related to a reduction of the monocyte-derived macrophage population and the Tnfa, Ccl2 and Lcn2 gene expression. As conclusion, boosting hepatic NADPH levels attenuated the oxidative lipid damage and the exhausted antioxidant gene expression specifically in female mice in two different models of NASH, preventing the progression of the inflammatory process and hepatic injury.

Digging Deeper, Zooming Out: Reimagining Legacies in Medical Education.

Although the wide-scale disruption precipitated by the COVID-19 pandemic has somewhat subsided, there are many questions about the implications of such disruptions for the road ahead. This year's Research in Medical Education (RIME) supplement may provide a window of insight. Now, more than ever, researchers are poised to question long-held assumptions while reimagining long-established legacies. Themes regarding the boundaries of professional identity, approaches to difficult conversations, challenges of power and hierarchy, intricacies of selection processes, and complexities of learning climates appear to be the most salient and critical to understand. In this commentary, the authors use the relationship between legacies and assumptions as a framework to gain a deeper understanding about the past, present, and future of RIME.

"A Look Under the Hood": Reflections on the Inaugural RIME Mentorship Program.

In 2021, Research in Medical Education (RIME) celebrated 60 years of advancing scholarship in health professions education (HPE). At that time, the nation's educational institutions faced a public reckoning on the long-standing pandemic of racism that sweltered in their practices and policies, laid bare by COVID-19 and the Black Lives Matters movement. RIME responded with a mentorship program for minoritized early career HPE faculty, which aims to amplify their voices in settings where their experiences and contributions are frequently dampened. The program fosters professional development through structured activities, participation as RIME committee interns, and formal mentorship channels to support career growth and offer experiences with scholarly publishing. This commentary was written by the first cohort of RIME mentees who are HPE scholars from various professions and diverse backgrounds with struggles traversing professional landscapes as immigrants and as individuals with minoritized identities and hopes for belonging in medical and educational institutions. In this commentary, the mentees describe the merits of the RIME mentorship program and what it meant to them and their unique marginalities. They also examine opportunities for improvements within the program to further reduce barriers faced by minoritized early career HPE faculty who often face limited support with scholarly activities.

Outcomes and Review in Surgery of Lateral Semicircular Canal Dehiscence in Cholesteatomatous Otitis Media: A Case Series.

Labyrinthine fistula is one of the most frequent complications of cholesteatoma otitis. We report two cases where a canal wall down mastoidectomy is made due to the characteristics of the cholesteatoma, achieving good outcomes in relation to bone conductive hearing. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03973-1.

De novo design of highly selective miniprotein inhibitors of integrins αvß6 and αvß8.

The RGD (Arg-Gly-Asp)-binding integrins αvß6 and αvß8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvß6 and αvß8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed. Here we describe a generalized method for computationally designing RGD-containing miniproteins selective for a single RGD integrin heterodimer and conformational state. We design hyperstable, selective αvß6 and αvß8 inhibitors that bind with picomolar affinity. CryoEM structures of the designed inhibitor-integrin complexes are very close to the computational design models, and show that the inhibitors stabilize specific conformational states of the αvß6 and the αvß8 integrins. In a lung fibrosis mouse model, the αvß6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

Tracheal Inflammatory Myofibroblastic Tumour ALK+ as Cause of Dyspnea in a 10 Years Old Child.

Inflammatory myofibroblastic tumours are rare lesions that could occur in airways. We report a 10 years old male who complains about dyspnea after physical exercise. Making CT and RMI images and a biopsy, we make an accurate diagnosis of an inflammatory myofibroblastic tumour ALK+. After treatment with a subtotal resection and crizotinib as adjuvant, we achieve a complete remission. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03775-5.