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Introdução: Além do coronavírus, a pandemia de COVID-19 trouxe uma carga emocional e psicológica extensa para toda sociedade, a qual afetou diversos grupos sociais e faixas etárias. Dessa forma, este trabalho tem como objetivo realizar uma revisão integrativa acerca dos transtornos mentais e os fatores a eles associados no Brasil pandêmico. Metodologia: Para proceder com tal estudo, foi realizado uma pesquisa bibliográfica de artigos pertinentes ao tema nos bancos de dados “SciElo” e “Lilacs”, utilizando de descritores definidos de acordo com os Descritores em Ciências da Saúde (DeCS), sendo eles: “infecções por coronavírus”, “ansiedade”, “depressão”. Resultados: Após a seleção com base nos critérios de inclusão e exclusão, foram selecionados 11 artigos para essa revisão. Discussão: A análise crítica dos artigos evidenciou a fragilidade da saúde mental de uma grande gama de indivíduos, dentre eles se destacaram os profissionais de saúde e as mulheres. Houve também um significativo aumento no número de casos de depressão, ansiedade e problemas relacionados ao sono. A incerteza sobre o futuro e a ausência de uma cura para o vírus foram fatores que se associaram com essas mazelas. Consequentemente, altos níveis de estresse, medo e angústia são percebidos pela população em geral que, por muitas vezes, acaba não procurando auxílio. Diante disso, ilustrou-se que práticas como Yoga e Reiki podem ser grandes ferramentas para uma boa saúde mental. Conclusão: Pode-se argumentar que a situação de dubiedade e grande receio tornou a sociedade suscetível a alterações na rotina e desencadeou novos padrões negativos na vida das pessoas, ameaçando seu bem-estar de várias maneiras. Para tanto, são necessárias ações que os motivem a buscar medidas, como a atividade física e até mesmo o tratamento terapêutico, visando o progresso e a consistência do estado de saúde mental.

GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism. Knocking out GATA4 in the adult liver (Gata4LKO) decreased transcriptional activity at GATA4 binding sites, especially during feeding. Gata4LKO mice have reduced plasma HDL cholesterol and increased liver triglyceride levels. The expression of a panel of GATA4 binding genes involved in hepatic cholesterol export and triglyceride hydrolysis was down-regulated in Gata4LKO mice. We further demonstrate that GATA4 collaborates with LXR nuclear receptors in the liver. GATA4 and LXRs share a number of binding sites, and GATA4 was required for the full transcriptional response to LXR activation. Collectively, these results show that hepatic GATA4 contributes to the transcriptional control of hepatic and systemic lipid homeostasis.

The aim of this study was to compare the 2-year outcomes of de novo versus postendovascular lesion treatment of femoropopliteal occlusions included in a national, multicenter, observational, prospective registry based on the treatment of critical Limb-threatening IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE) registry.From January 2018 to December 2019, 541 patients from 43 centers have been enrolled in the LIMBSAVE registry. Of these patients, 460 were included in the present study: 341 (74.1%) with de novo lesions (DN group) and 119 (25.9%) with postendovascular treatment lesions (PE group). Initial outcome measures were assessed at 30 days after treatment. Furthermore, at the 2-year follow-up, the estimated outcomes of primary patency, primary-assisted patency, secondary patency, and limb salvage were analyzed with Kaplan-Meier curves and compared between groups with the log-rank test.Both groups were homogeneous in terms of demographic data, preoperative risk factors, and clinical presentation. However, compared with DN group, more patients in PE group had a great saphenous vein diameter of less than 3 mm (11.1% vs 21%; P = .007). Intraoperatively, both groups showed similar distal anastomosis sites: below-the-knee popliteal artery (63% DN group, 66.4% PE group) and tibial vessel (37% DN group, 33.6% PE group) (P = .3). The overall mean duration of follow-up was 11.6 months (range, 1-24 months). At the 2-year follow-up, there were no differences between the two groups in terms of primary patency (66.3% DN group vs 74.1% PE group; P = .9), primary-assisted patency (78.2% DN group vs 79.5% PE group; P = .2), secondary patency (85.1% DN group vs 91.4% PE group; P = .2), and limb salvage (95.2% DN group vs 95.1% PE group; P = .9).The LIMBSAVE registry did not show a worsening of overall patency and limb salvages rates at the 2-year follow-up in patients undergoing in situ saphenous bypass after a failed endovascular approach for long femoropopliteal occlusive disease. This finding is in contrast with what has been published in literature.

Abstract Introduction During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients. Objective To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients. Methods The EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10–20 μV) or suppressed ( Results Among 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate. Conclusions EEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

Iron supplementation improves the erythropoiesis-stimulating agents' (ESAs) response in chemotherapy-related anemia. The primary aim of our study is to assess the efficacy of sucrosomial iron, a new oral iron formulation, in cancer patients with chemotherapy-induced anemia treated with ESAs. The secondary objectives included the efficacy into two subgroups of patients (iron replete and functional iron deficiency) between the two study arms, safety and the effect on transfusion need.In this randomized, multicentre, open-label, phase III clinical trial, 60 cancer patients were enrolled. Each patient was randomly assigned (1:1) to receive 12 weeks of oral sucrosomial iron at the dose of 30 mg daily in combination with ESAs or no supplementation to ESA treatment. The endpoint considered for efficacy was the proportion of patients achieving complete hematological response at 12 weeks (increase in Hb 2 g/dL from baseline, without RBC transfusions in the previous 28 days or achieving Hb ≥ 12 g/dL).There was a statistically significant association between oral sucrosomial iron supplementation in combination with ESAs and the achievement of a complete hematological response. This response was achieved within 12 weeks by 31% of patients in the control group and by 52% of patients supplemented with oral sucrosomial iron. A trend of greater response in sucrosomial iron arm was found in both subgroups. No difference was observed about safety and transfusion need.Sucrosomial iron is well tolerated and its combination with ESAs improves the hematological response in cancer patients with chemotherapy-related anemia.This study has been reviewed by the Institutional Ethics Committee of the IRCCS Policlinico San Matteo Foundation, Pavia, Italy (28/04/2015; prot. N. 20,150,002,059), and by the Institutional Ethics Committee of the other Italian oncological centers involved in this study.

Introduction/background: This single-arm, phase 2, multi-center, study aims to assess the safety and efficacy of a regimen of induction chemo-immunotherapy followed by de-intensified, hypo-fractionated thoracic radiotherapy (RT) given concurrently with durvalumab and maintenance durvalumab in patients with unresectable, stage III NSCLC. Material and methods: we will enroll 45 patients with unresectable stage III NSCLC, any PD-L1, deemed ineligible for concurrent CRT by a thoracic oncology multidisciplinary team, and candidate to sequential chemoradiation followed by durvalumab. Results: Primary endpoint is safety, defined by the incidence of grade 3 and 4 possibly related adverse events (PRAEs) within 6 months from the initiation of treatment. The secondary objectives are PFS and OS (median and 12 months). Ancillary endpoints are molecular response evaluated by cfDNA isolation baseline, after chemo-immuno RT and at progression, and radiomics analysis on CT scans at baseline and before maintenance. Conclusion: DEDALUS phase 2 trial explores the safety and efficacy of a novel sequence of chemo-radiation (with de-intensified RT) plus the anti-PD-L1 agent durvalumab in patients with stage III unresectable NSCLC who are candidates to sequential chemoradiation plus maintenance immunotherapy.

PurposeThe purpose of this article is to investigate the interrelationships between innovation climate and human capital in the development of dynamic capabilities related to innovation. The study presents a set of concepts about variables involved in the innovation process and their interrelationship, addressing the analysis of international scientific production related to the antecedents of the innovation climate, human capital and dynamic capabilities.Design/methodology/approachA review of the literature from 1998 to 2018 was carried out, using descriptive statistical methods, at first, and qualitative analysis of the results in order to visualize the current configuration of the field of study of innovation background.FindingsThe results demonstrate a significant number of studies relating human capital and dynamic capabilities and little quantitative significance in studies relating to a climate of innovation and dynamic capabilities. The research describes how the dynamic capabilities of innovation have been approached in a conceptual model based on the perspective of human capital and innovation climate.Research limitations/implicationsThe study did not contemplate the analysis of the interrelationship between the resource configuration construct and the dynamic innovation capacities (part of the gap pointed out by Tuzovic, Wirtz and Heracleous (2018), constituting a perceptible limitation of the analyzes carried out in this article.Practical implicationsThe influence of the innovation climate construct and its relationship with dynamic innovation capabilities deserves greater attention in research with an empirical approach, constituting a field to be explored by scientific research in organizations.Originality/valueThe research sought to investigate the gap involving the interrelations between innovation climate and human capital in the development of dynamic capabilities related to innovation, indicating the need for further empirical studies on the subject.

Introduction: US National Cancer Institute’s (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. Methods: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). Results: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). Discussion: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.

Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

We analyse the effectiveness of financial reforms in the transition economy of Vietnam, from the early years until the present day. Our focus is on the changes and the determinants of banks cost efficiency, which was widely criticised and was the focus of the reforms package. We find that regulatory changes impact favourably the development of the sector. Technological and efficiency improvements characterise the period of analysis, helped by better capitalisation and increased diversification. Any technological spillovers from foreign banks are quickly transferred to the domestic market, and larger domestic banks rapidly become the best performing institutions, in support of the more recent liberalisation and privatisation policies.

Objective: To analyze the scientific production related to the market performance in the high-tech market from 1997 to 2019. Method: Bibliometrics and systematic review methodologies were used. The search process was performed in the Web of Science and SPELL databases and resulted in the selection of 23 articles within the defined scope, among 82 studies. The selected studies were analyzed through descriptive statistics, Descending Hierarchical Classification (DHC) and Corresponding Factor Analysis (CFA).Results: The results point to recent interest in measuring performance in the high-tech market, especially in emerging markets such as Taiwan and China, with the use of multidimensional indicators of a financial and non-financial nature. Through the DHC and CFA analyses, we have been able to observe four Classes - ‘Internal Abilities’, ‘Alliances’, ‘Downstream Focus’ and ‘Upstream Focus’ – and these dominant areas indicate the interest associated with market performance in the high-tech market.Originality/relevance: The study innovates by proposing a protocol to perform textual analysis of scientific articles with the aid of Iramuteq software, enabling the identification of different approaches of the studies and grouping by similarities.Contributions: We propose an agenda for future studies based on the results and gaps about performance and indicators used by companies in the high-tech market. From the managerial point of view, it is noteworthy that the most used indicators in this market are sales, market share and new product performance., Objetivo: Analizar la producción científica relacionada con el desempeño del mercado en el mercado de alta tecnología de 1997 a 2019.Método: Las metodologías Bibliometría y revisión sistemática se utilizaron. El proceso de búsqueda se realizó en las bases de datos Web of Science y SPELL y resultó en la selección de 23 artículos dentro del alcance definido, entre 82 estudios. Los estudios seleccionados se analizaron mediante estadística descriptiva, clasificación jerárquica descendente (CHD) y análisis de factores de correspondencia (AFC).Resultados principales: Los resultados apuntan al interés reciente en medir el desempeño en el mercado de alta tecnología, especialmente en mercados emergentes como Taiwán y China, utilizando indicadores multidimensionales, financieros y no financieros. A través de los análisis CHD y AFC, se formaron cuatro clases – 'Habilidades internas', 'Alianzas', 'Enfoque descendente' y 'Enfoque ascendente' – cuyos temas predominantes explican el foco de interés asociado con el desempeño del mercado en el mercado de alta tecnología.Relevancia/Originalidad: El estudio innova al proponer un protocolo para realizar análisis textuales de artículos científicos con la ayuda del software Iramuteq, que permite la identificación de diferentes enfoques de los estudios y agrupación por similitudes.Contribuciones: Se propone una agenda de estudios futuros basada en los resultados y las brechas en el desempeño y los indicadores utilizados por las empresas en el mercado de alta tecnología. Desde el punto de vista gerencial, es notable que los indicadores más utilizados en este mercado son las ventas, la participación en el mercado y el rendimiento de los nuevos productos., Objetivo: Analisar a produção científica relativa ao desempenho mercadológico no mercado de alta tecnologia no período de 1997 a 2019.Método: Foram utilizadas as metodologias de bibliometria e revisão sistemática. O processo de busca foi realizado nas bases Web of Science e SPELL e resultou na seleção de 23 artigos dentro do escopo definido, dentre 82 estudos. Os estudos selecionados foram analisados por meio de estatística descritiva, Classificação Hierárquica Descendente (CHD) e Análise Fatorial de Correspondência (AFC).Principais resultados: Os resultados apontam um recente interesse sobre a mensuração de desempenho no mercado de alta tecnologia, sobretudo nos mercados emergentes como Taiwan e China, com o uso de indicadores multidimensionais, financeiros e não financeiro. Por meio das análises de CHD e AFC observou-se a formação de quatro Classes – ‘Habilidades internas’, ‘Alianças’, ‘Foco a jusante’ e ‘Foco a montante’ – cujas temáticas predominantes explicitam os focos de interesse associados ao desempenho mercadológico no mercado de alta tecnologia.Relevância/originalidade: O estudo inova ao propor um protocolo para realizar análises textuais de artigos científicos com auxílio do software Iramuteq, possibilitando a identificação dos diferentes enfoques dos estudos e agrupamento por semelhanças.Contribuições: É proposta uma agenda de estudos futuros em função dos resultados e de lacunas sobre desempenho e indicadores utilizados pelas empresas no mercado de alta tecnologia. Sob o prisma gerencial, destaca-se que os indicadores mais utilizados nesse mercado são as vendas, a participação de mercado e o desempenho de novos produtos.

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

Despite impressive progress, nearly two billion people worldwide have no access to essential medicines. The COVID-19 pandemic revealed Africa’s vulnerability due to its reliance on imports for most vaccines, medicines, and other health product needs. The vaccine manufacturing is complex and requires massive financial investments, with global, regional, and national regulatory structures introducing consistent and urgent reforms to assure the quality and safety of medicines. In 2020, there were approximately 600 pharmaceutical manufacturers in Africa, 80% of which were concentrated in eight countries: Egypt, Algeria, Morocco, Tunisia, Nigeria, Ghana, Kenya, and South Africa. Only 4 countries had more than 50 manufacturers, while 22 countries had no local production. Out of the 600, around 25% were multinational companies. Africa is equally affected by modest scaled capacities substantially engaging in packaging and labelling, and occasionally fill and finish steps, facing criticalities in terms of solvent domestic markets. This article discusses the challenges in the development of a local pharmaceutical manufacturing in Africa and reflects on the importance of the momentum for strengthening the local medical production capacity in the continent as a critical opportunity for advancing universal health coverage (UHC).

The aim was to demonstrate contemporary outcomes of in situ saphenous vein bypass using a valvulotome.Analysis of two year outcomes of a multicentre registry based on the treatment of critical Limb Ischaemia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE). Between January 2018 and December 2019, 541 patients in 43 centres were enrolled. In all patients an innovative valvulotome was used. Early outcomes were assessed. Two year outcomes according to Kaplan-Meier curves in terms of patency and limb salvage were evaluated. Associations between patient and procedure variables were analysed with univariable and multivariable analyses.In all cases, a valvulotome was able to lyse the valves. Vein injury due to the in situ technique was 3.5%. Thirty day mortality and major amputation rates were 3% and 0.9%, respectively. Mean follow up was 12.1 months. Two year estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 69.1%, 81.4%, 86.5%, and 94.5%, respectively. Multivariable analysis showed an association between pre-operative vein diameter3 mm and lower primary patency (hazard ration [HR] 14.3, p.001), primary assisted patency (HR 9.4, p = .002), secondary patency (HR 7.2, p = .007), and limb salvage (HR 7.8, p = .005) rates. Distal anastomosis to a tibial or foot vessel was also associated with lower primary patency (HR 4.8, p = .033), and primary assisted patency (HR 6, p = .011) rates. Use of a suprafascial tributary collateral as a graft was associated with lower primary patency (HR 6.7, p = .013), and primary assisted patency (HR 4.2, p = .042) rates.Vein diameter3 mm, distal anastomosis on a tibial or foot vessel, and use of a suprafascial tributary collateral as a graft were significantly associated with loss of patency and limb loss during follow up.

In recent years, whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. The aim of this study was to evaluate the benefit of WP isolate (WPI) supplementation in addition to nutritional counseling in malnourished advanced cancer patients undergoing chemotherapy (CT). In a single‐center, randomized, pragmatic, and parallel‐group controlled trial (http://www.ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer patients with mixed tumor entities candidate to or undergoing CT were randomly assigned to receive nutritional counseling with (N = 82) or without (N = 84) WPI supplementation (20 g/d) for 3 months. The primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat‐free mass index (FFMI), body weight, muscle strength, and CT toxicity (CTCAE 4.0 events). In patients with the primary endpoint assessed (modified intention‐to‐treat population), counseling plus WPI (N = 66) resulted in improved PhA compared to nutritional counseling alone (N = 69): mean difference, 0.48° (95% CI, 0.05 to 0.90) (P = .027). WPI supplementation also resulted in improved SPA (P = .021), FFMI (P = .041), body weight (P = .023), muscle strength (P, Whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. In malnourished advanced cancer patients undergoing chemotherapy (CT) and receiving nutritional counseling, a 3‐month supplementation with WP resulted in improved body composition, muscle strength, and reduced CT toxicity.

A key research question that remains largely unanswered especially in the African context is whether the macroeconomic environment and the level of financial development of a country determine the effectiveness of financial reforms. This has important policy implications. We choose Ghana as a case study and carry out an in-depth analysis of its comprehensive set of financial reforms, implemented in the 2000s, which we look at individually. We estimate a stochastic cost frontier to look at efficiency. This is then followed by two different models of competition on the loans market, the main target of the reforms. We find that only the removal of entry restrictions is significant at improving banks efficiency and that private and global foreign, but not regional banks, benefit from it. The results show, however, no improvements in competition, and reveal instead that macroeconomic and institutional weaknesses continue to exert a negative counterbalancing effect. Reforms need to be anchored on stronger macroeconomic fundamentals, institutional initiatives and generally stronger credit environments for their full potential to be revealed in the context of developing financial markets.

Background & aims: To investigate the association between the parameters used in nutritional screening assessment (body mass index [BMI], unintentional weight loss [WL] and reduced food intake) and clinical outcomes in non-critically ill, hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: This was a prospective multicenter real-life study carried out during the first pandemic wave in 11 Italian Hospitals. In total, 1391 patients were included. The primary end-point was a composite of in-hospital mortality or admission to ICU, whichever came first. The key secondary end-point was in-hospital mortality. Results: Multivariable models were based on 1183 patients with complete data. Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was found to have a negative prognostic impact for both the primary and secondary end-point (P < .001 for both). No association with BMI and WL was observed. Other predictors of outcomes were age and presence of multiple comorbidities. A significant interaction between obesity and multi-morbidity (≥2) was detected. Obesity was found to be a risk factor for composite end-point (HR = 1.36 [95%CI, 1.03–1.80]; P = .031) and a protective factor against in-hospital mortality (HR = 0.32 [95%CI, 0.20–0.51]; P < .001) in patients with and without multiple comorbidities, respectively. Secondary analysis (patients, N = 829), further adjusted for high C-reactive protein (>21 mg/dL) and LDH (>430 mU/mL) levels yielded consistent findings. Conclusions: Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was associated with negative clinical outcomes in non-critically ill, hospitalized COVID-19 patients. This simple and easily obtainable parameter may be useful to identify patients at highest risk of poor prognosis, who may benefit from prompt nutritional support. The presence of comorbidities could be the key factor, which may determine the protective or harmful role of a high body mass index in COVID-19.

Background Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient’s age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. Methods A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. Results Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. Conclusions The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

Recent studies have demonstrated the existence of a discrete pool of cholesterol in the plasma membranes (PM) of mammalian cells-referred to as the accessible cholesterol pool-that can be detected by the binding of modified versions of bacterial cytolysins (e.g., anthrolysin O). When the amount of accessible cholesterol in the PM exceeds a threshold level, the excess cholesterol moves to the endoplasmic reticulum (ER), where it regulates the SREBP2 pathway and undergoes esterification. We reported previously that the Aster/Gramd1 family of sterol transporters mediates nonvesicular movement of cholesterol from the PM to the ER in multiple mammalian cell types. Here, we investigated the PM pool of accessible cholesterol in cholesterol-loaded fibroblasts with a knockdown of Aster-A and in mouse macrophages from Aster-B and Aster-A/B-deficient mice. Nanoscale secondary ion mass spectrometry (NanoSIMS) analyses revealed expansion of the accessible cholesterol pool in cells lacking Aster expression. The increased accessible cholesterol pool in the PM was accompanied by reduced cholesterol movement to the ER, evidenced by increased expression of SREBP2-regulated genes. Cosedimentation experiments with liposomes revealed that the Aster-B GRAM domain binds to membranes in a cholesterol concentration-dependent manner and that the binding is facilitated by the presence of phosphatidylserine. These studies revealed that the Aster-mediated nonvesicular cholesterol transport pathway controls levels of accessible cholesterol in the PM, as well as the activity of the SREBP pathway.