Role of protein kinase C and NF-κB in proteolysis-inducing factor-induced proteasome expression in C2C12 myotubes

Proteolysis-inducing factor (PIF) is a sulphated glycoprotein produced by cachexia-inducing tumours, which initiates muscle protein degradation through an increased expression of the ubiquitin–proteasome proteolytic pathway. The role of kinase C (PKC) in PIF-induced proteasome expression has been studied in murine myotubes as a surrogate model of skeletal muscle. Proteasome expression induced by PIF was attenuated by 4alpha-phorbol 12-myristate 13-acetate (100 nM) and by the PKC inhibitors Ro31-8220 (10 muM), staurosporine (300 nM), calphostin C (300 nM) and Gö 6976 (200 muM). Proteolysis-inducing factor-induced activation of PKCalpha, with translocation from the cytosol to the membrane at the same concentration as that inducing proteasome expression, and this effect was attenuated by calphostin C. Myotubes transfected with a constitutively active PKCalpha (pCO2) showed increased expression of proteasome activity, and a longer time course, compared with their wild-type counterparts. In contrast, myotubes transfected with a dominant-negative PKCalpha (pKS1), which showed no activation of PKCalpha in response to PIF, exhibited no increase in proteasome activity at any time point. Proteolysis-inducing factor-induced proteasome expression has been suggested to involve the transcription factor nuclear factor-kappaB (NF-kappaB), which may be activated through PKC. Proteolysis-inducing factor induced a decrease in cytosolic I-kappaBalpha and an increase in nuclear binding of NF-kappaB in pCO2, but not in pKS1, and the effect in wild-type cells was attenuated by calphostin C, confirming that it was mediated through PKC. This suggests that PKC may be involved in the phosphorylation and degradation of I-kappaBalpha, induced by PIF, necessary for the release of NF-kappaB from its inactive cytosolic complex

Starting-up unregistered and firm performance in Turkey

© 2016 The Author(s) Recent years have seen a questioning of the negative representation of informal sector entrepreneurship and an emergent view that it may offer significant benefits. This paper advances this rethinking by evaluating the relationship between business registration and future firm performance. Until now, the assumption has been that starting-up unregistered is linked to weaker firm performance. Using World Bank Enterprise Survey data on 2494 formal enterprises in Turkey, and controlling for other determinants of firm performance as well as the endogeneity of the registration decision, the finding is that formal enterprises that started-up unregistered and spent longer unregistered have significantly higher subsequent annual sales and productivity growth rates compared with those registered from the outset. This is argued to be because in such weak institutional environments, the advantages of registering from the outset are outweighed by the benefits of deferring business registration and the low risks of detection and punishment. The resultant implication is that there is a need to shift away from the conventional eradication approach based on the negative depiction of informal entrepreneurship as poorly performing, and towards a more facilitating approach that improves the benefits of business registration and tackles the systemic formal institutional deficiencies that lead entrepreneurs to decide to delay the registration of their ventures

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Change of chemical constitution of the traditional Macedonian sausage kept of different temperatures

This study reports the changes that occur at vacuum packed Macedonian sausage produced in the traditional way during the storage in cooling chamber at different temperature conditions of 6 C an 15 C. Changes that occur during the storage were examined on 2, 15, 25 and 50 day from production. It was determined that during the storage time of the sausages substantial changes occur in the decreasing content of proteins, fats and mineral materials. The total number of bacteria in the sausages increases during the storage mostly of those at 15 C. Best sensor characteristics till the 50 day showed the sausage kept on 6 C

Cancrum nasalis: a case report

Cancrum nasalis, a variant of cancrum oris, is an oro-facial condition that is rarely reported in the literature. Predisposing factors include malnutrition, infection and reduced immunity. This paper reports a case of a 10 month-old child patient who presented with an isolated necrosis of the nose extending to the cutaneous part of the upper lip without oral manifestation, a rare clinical presentation. A maculo-papular rash which was diagnosed as measles preceeded the necrosis of the nose and the child was also seen to be malnourished at presentation. Laboratory investigations and clinical management of the condition are described. It is also suggested that the public should be continuosly educated on the importance of balanced diet and routine medical check for growing children. Keywords: Cancrum nasalis, malnutritionNigerian Dental Journal Vol. 16 (1) 2008: pp. 32-3

Recent Advances on Type-2 Cannabinoid (CB2) Receptor Agonists and their Therapeutic Potential

In the last decade, selective modulators of type-2 cannabinoid receptor (CB2) have become a major focus to target endocannabinoid signaling in humans. Indeed, heterogeneously expressed within our body, CB2 actively regulates several physio-patho-logical processes, thus representing a promising target for developing specific and safe therapeutic drugs. If CB2 modulation has been extensively studied since the very beginn-ing for the treatment of pain and inflammation, the more recent involvement of this receptor in other pathological conditions has further strengthened the pursuit of novel CB2 agonists in the last five years. Against this background, here we discuss the most recent evidence of the protective effects of CB2 against pathological conditions, emphasizing central nervous system disor-ders, bone and synovial diseases, and cancer. We also summarize the most recent advances in the development of CB2 agonists, focusing on the correlation between different chemical classes and diverse therapeutic applications. Data mining includes a review of the CB2 ligands disclosed in patents also released in the last five years. Finally, we discuss how the recent elucidation of CB2 tertiary structure has provided new details for the rational design of novel and more selective CB2 agonists, thus supporting innovative strategies to develop effective therapeutics. Our overview of the current knowledge on CB2 agonists provides pivotal information on the structure and function of different classes of molecules and opens possible avenues for future research

Tradução e adaptação transcultural para o português brasileiro da Scale for Quality of Sexual Function (QSF) Translation and cross-cultural adaptation into Brazilian Portuguese of the Scale for Quality of Sexual Function (QSF)

INTRODUÇÃO: Apesar do papel fundamental da função sexual na qualidade de vida da população, há uma escassez na literatura brasileira de instrumentos específicos para sua avaliação e que possam ser utilizados tanto para homens quanto para mulheres. A adaptação da Scale for Quality of Sexual Function (QSF), uma escala unissex, é um passo importante na obtenção de instrumentos que permitam a comparação de resultados entre diferentes populações. OBJETIVO: Descrever o processo de tradução e adaptação semântica da QSF para o português brasileiro. MÉTODOS: A adaptação do instrumento envolveu cinco fases: 1) duas traduções independentes, 2) uma versão de consenso realizada por tradutores e especialistas, 3) avaliação da versão gerada por mais um especialista que não participou das etapas anteriores, 4) retrotradução com avaliação do autor da escala original e, por fim, 5) aplicação da versão obtida em um grupo experimental. RESULTADOS: São descritas todas as etapas de adaptação do instrumento. A participação de especialistas tanto da área de saúde mental quanto de sexualidade humana, desde a primeira fase do processo, contribuiu para discussões amplas, que permitiram a melhor adequação dos itens, tanto conceitual quanto culturalmente. Participaram da aplicação experimental sujeitos de diferentes níveis de escolaridade de ambos os sexos, não sendo detectadas dificuldades na compreensão dos itens. CONCLUSÃO: Por meio dos procedimentos adotados, foi possível elaborar uma versão da QSF em português brasileiro.<br>INTRODUCTION: Despite the important role played by sexual function in quality of life, there is a scarcity of instruments in the Brazilian literature specifically designed to assess this aspect, and especially of instruments that can be used with both men and women. The adaptation of the Scale for Quality of Sexual Function (QSF), a unisex scale, is an important step in the production of instruments that allow to compare results obtained in different populations. OBJECTIVE: To describe the translation and semantic adaptation of the QSF into Brazilian Portuguese. METHODS: Instrument adaptation involved five phases: 1) two independent translations, 2) a consensual version produced by translators and experts, 3) evaluation of this version by a different expert, not involved in the previous phases, 4) back translation with evaluation by the author of the original scale, and, finally, 5) application of the final Brazilian Portuguese version in a experimental group. RESULTS: All stages of the adaptation process are described. The participation of experts from the fields of both mental health and human sexuality since the first stage of the process contributed to broader discussions, which allowed to achieve the best possible adequacy for each item, both conceptually and culturally. The experimental application of the final, adapted version of the scale involved both men and women with different educational backgrounds and levels. No difficulties were faced by this group in understanding the items included in the scale. CONCLUSION: The procedures and process herein described successfully allowed to develop a Brazilian Portuguese version of the QSF