Ketogenic Diet and Weight Loss: Is There an Effect on Energy Expenditure?

A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or "keto" diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-beta-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals

FRESH CUT VEGETABLE: BREATHABLE FILM

The importance of minimally processed vegetables is increasing since the consumer requires products that keep their health properties, as well as their freshness and nutritional values. The deterioration processes of fresh-cut vegetables can be retarded by using suitable pre-treatments and/or adequate packaging systems, besides/ in addition to storage temperature. Fresh produce continue to respire in a post-harvest environment. Once the produce is packed, film with relatively high oxygen (O2) permeability must be used to avoid the risk of anaerobic respiration and excessive carbon dioxide (CO2) levels within the packages (2). In this paper, we will analyse how the use of specific raw materials and/or process conditions, has led to the production of film with the unique combination of high oxygen transmission, with relatively low water vapour transmission rate, and excellent optical and stiffness performances. Moreover, we will analyse how the film performs and affects the shelf life of fresh cut vegetables

Illness Experiences and Attitudes towards Medication in Online Communities for People with Fibromyalgia

Abstract: Fibromyalgia is a chronic disabling syndrome, and the legitimacy of its diagnosis is still debated. Internet and online communities may become a relevant resource for affected people. This present study aims to understand the role of online communities relating to fibromyalgia syndrome (FMS) patients’ illness experiences and their attitudes towards medication. A qualitative content analysis based on the grounded theory approach was conducted on 19 conversations from an online forum, and 14 online interviews. Illness experience, lack of reference points, online communities, personal role and attitude towards medication were the five categories identified, with the search for recognition as the core category. The study highlighted that online communities represent a resource that allows users to express and share their needs, especially in terms of legitimacy and recognition

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed

Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma.

SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB

Immunological features of patients affected by Barraquer-Simons syndrome

Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. Results: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti- FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population). Conclusions: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.This work was supported by Instituto de Salud Carlos III (Ministerio de Ciencia, Innovación y Universidades, Gobierno de España) and Fondos FEDER (PI15–00255 to M.L-T. and PI08–1449 to D.A-V.), Complemento II-CM network (B2017/BMD3673 to M.L-T), the intramural research program of the Xunta de Galicia (Programa de Consolidación e Estructuración de Unidades de Investigación Competitivas, grant ED341b 2017/19 to D.A-V.), the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP) (to D.A-V., to F.C. and to P.N.

Parâmetros meteorológicos e infecção hospitalar de corrente sanguínea: estudo caso-referência

OBJECTIVE To evaluate if temperature and humidity influenced the etiology of bloodstream infections in a hospital from 2005 to 2010. METHODS The study had a case-referent design. Individual cases of bloodstream infections caused by specific groups or pathogens were compared with several references. In the first analysis, average temperature and humidity values for the seven days preceding collection of blood cultures were compared with an overall “seven-days moving average” for the study period. The second analysis included only patients with bloodstream infections. Several logistic regression models were used to compare different pathogens and groups with respect to the immediate weather parameters, adjusting for demographics, time, and unit of admission. RESULTS Higher temperatures and humidity were related to the recovery of bacteria as a whole (versus fungi) and of gram-negative bacilli. In the multivariable models, temperature was positively associated with the recovery of gram-negative bacilli (OR = 1.14; 95%CI 1.10;1.19) or Acinetobacter baumannii (OR = 1.26; 95%CI 1.16;1.37), even after adjustment for demographic and admission data. An inverse association was identified for humidity. CONCLUSIONS The study documented the impact of temperature and humidity on the incidence and etiology of bloodstream infections. The results correspond with those from ecological studies, indicating a higher incidence of gram-negative bacilli during warm seasons. These findings should guide policies directed at preventing and controlling healthcare-associated infections.OBJETIVO Avaliar se temperatura e umidade influenciam a etiologia das infecções na corrente sanguínea em hospital, no período de 2005 a 2010. MÉTODOS O estudo teve delineamento caso-referência. Casos individuais de infecções de corrente sanguínea por patógenos ou grupos de interesse foram comparados com diferentes referências. Na primeira etapa, valores médios de temperatura e umidade, para os sete dias que precederam a coleta de culturas de sangue, foram comparados com a “média-móvel de ordem 7” para todos os dias do período do estudo. A segunda etapa incluiu somente os casos com culturas positivas. Foram realizadas análises por regressão logística para avaliar a influência dos parâmetros meteorológicos imediatos sobre a etiologia dessas infecções, ajustando os resultados para dados demográficos, tempo e unidade de internação. RESULTADOS Temperatura e umidade mais elevadas foram associadas às infecções de corrente sanguínea causadas por bactérias como um todo (versus fungos) e por bacilos Gram-negativos. Nos modelos multivariados, a temperatura foi positivamente associada com o isolamento nas culturas de bacilos Gram-negativos (OR = 1,14; IC95% 1,10;1,19) ou A. baumannii (OR = 1,26; IC95% 1,16;1,37), mesmo após ajuste para dados demográficos e de internação. Associação inversa foi identificada por umidade. CONCLUSÕES O estudo documentou o impacto de temperatura e umidade sobre incidência e etiologia de infecções da corrente sanguínea. Os resultados são coerentes com os relatados em estudos ecológicos, apontando para maior incidência de bacilos Gram-negativos durante as estações quentes. Esses achados devem orientar as estratégias direcionadas à prevenção e controle de infecções relacionadas à assistência à saúde

Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation

The aberrant activation of hedgehog (HH) signaling is a leading cause of the development of medulloblastoma, a pediatric tumor of the cerebellum. The FDA‑approved HH inhibitor, Vismodegib, which targets the transmembrane transducer SMO, has shown limited efficacy in patients with medulloblastoma, due to compensatory mechanisms that maintain an active HH‑GLI signaling status. Thus, the identification of novel actionable mechanisms, directly affecting the activity of the HH‑regulated GLI transcription factors is an important goal for these malignancies. In this study, using gene expression and reporter assays, combined with biochemical and cellular analyses, we demonstrate that mitogen‑activated kinase kinase kinase 1 (MEKK1), the most upstream kinase of the mitogen‑activated protein kinase (MAPK) phosphorylation modules, suppresses HH signaling by associating and phosphorylating GLI1, the most potent HH‑regulated transcription factor. Phosphorylation occurred at multiple residues in the C‑terminal region of GLI1 and was followed by an increased association with the cytoplasmic proteins 14‑3‑3. Of note, the enforced expression of MEKK1 or the exposure of medulloblastoma cells to the MEKK1 activator, Nocodazole, resulted in a marked inhibitory effect on GLI1 activity and tumor cell proliferation and viability. Taken together, the results of this study shed light on a novel regulatory mechanism of HH signaling, with potentially relevant implications in cancer therapy

Coworking: uma revisão sistemática

Este trabalho pretendeu despender um olhar científico sobre o coworking, um espaço de trabalho compartilhado por profissionais independentes e remotos. Trata-se de um fenômeno crescente em várias cidades e diferentes nações, porém novo para a ciência (Spinuzzi, 2012; Capdevila, 2014a & 2014b; Gerdenitsch, Sheel, Andorfer e Korunka (2016). Neste contexto, foi desenvolvido um estudo com abordagem quali-quantitativo, e descritivo bibliográfico, por meio de revisão sistemática, em que a bibliometria foi utilizada para análise de dados. Neste levantamento, a maioria das obras localizadas foi de origem europeia, com abordagem qualitativa e natureza exploratória e descritiva. Em relação aos conceitos, teorias e resultados, diversos dados foram observados entre os estudos selecionados, como, por exemplo, o enfoque das pesquisas e a questão da necessidade das pessoas que utilizam os espaços coworking (social, econômica ou profissional). Foi oferecida atenção a esse quesito em todos os estudos localizados nesta busca, seja a necessidade em aspecto social, econômico ou profissional. Sobre a possível relação entre secretariado executivo e coworking, percebem-se pontos comuns na literatura dos temas. Para as possíveis dificuldades relacionadas à rotina do secretário remoto, os espaços coworking podem proporcionar as soluções. Sugere-se, para pesquisas futuras, estudo referente à produtividade dos usuários do coworking e investigação referente à questão da sustentabilidade financeira desses lugares

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico⁻chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors