Chemical characterization and bioactivities of sericin extracted from silkworm cocoons from two regions of Portuga

Along the years, sericin has been undervalued and discarded as waste from the textile silk industry. However, recent studies have shown that sericin has great potential for biomedical applications. The potential for medicinal applications depends on its physicochemical properties and molecular heterogeneity. In addition, the characteristics of sericin are influenced by its extraction method, its origin and the variety of cocoon. This work aimed to characterize the biochemical and bioactivities of sericin from Bragança and Castelo Branco. Sericin was extracted using the autoclave method, and its physicochemical properties were then characterized by analyzing its amino acid content by HPLC. In addition, its potential for antioxidant by TBARS and CAA assays, anti- inflammatory by NO inhibition, antimicrobial by microdilution method, anti-proliferative by SBR assay, and anticoagulant activities by APTT method was evaluated. In its pure state, sericin did not have a high content of free amino acids, with tyrosine being identified as the most abundant. On the other hand, when hydrolyzed sericin showed a higher content of amino acids and serine was the most abundant. In terms of bioactivities, the sericin tested did not show antioxidant or anti-inflammatory potential in the tests carried out. Despite this, it showed anti-proliferative activity in contact with human tumor cell lines and in non-tumor cell lines at a minimum concentration of 0.52 and 0.32 mg /mL, respectively. As far as antimicrobial activity is concerned, sericin proved capable of inhibiting the growth of the bacteria and fungi tested at concentrations between 5 and 10 mg/mL. Finally, sericin was also shown to be able to prolong the coagulation time in adult mice plasma, presenting anticoagulant potential. The sericin from Bragança and Castelo Branco, collected in 2019, did not differ greatly, differences in amino acid composition were identified. In addition, the sericin collected in Bragança in 2021 and 2022, S3 and S4, respectively, showed differences compared to the other samples and showed the best antiproliferative, antibacterial and anticoagulant potential. Additionally, there are also differences between extracted and commercial samples.Ao longo do tempo, a sericina foi desvalorizada e descartada como resíduo da indústria têxtil da seda, no entanto, estudos recentes comprovam o grande potencial da sericina em aplicações biomédicas. O potencial para aplicações medicinais depende das suas propriedades físico-químicas e heterogeneidade molecular. Além disso, as características da sericina são influenciadas pelo seu método de extração, a sua origem e a variedade do casulo. Este trabalho teve como objetivo a caracterização bioquímica e bioactiva da sericina com origem em Bragança e Castelo Branco. A sericina foi extraída através do método da autoclave, e, posteriormente as propriedades físico-químicas foram caracterizadas através da análise do teor de aminoácidos por HPLC. Além disso, foi avaliado o seu potencial para as atividades antioxidante pelos ensaios TBARS e CAA, anti-inflamatória pela inibição de NO, antimicrobiana pelo método da microdiluição, anti proliferativa pelo método SRB, e, anticoagulante pelo método APTT. No seu estado puro, a sericina não apresentou um grande teor de aminoácidos livres, tendo sido identificado como mais abundante a tirosina. Por outro lado, quando hidrolisada, a sericina apresentou um teor mais elevado, sendo a serina a mais abundante. Relativamente às bioatividades, a sericina testada não apresentou potencial antioxidante nem anti-inflamatória nos ensaios realizados. Apesar disso, apresentou atividade anti proliferativa em contacto com linhas celulares tumorais humanas e em linhas celulares não tumorais a uma concentração mínima de 0.52 e 0.32 mg /mL, respectivamente. Relativamente à atividade antimicrobiana, a sericina mostrou ser capaz de inibir o crescimento das bactérias e fungos testados para concentrações compreendidas entre 5 e 10 mg/ mL. A sericina também mostrou ser capaz de prolongar o tempo de coagulação em plasma de ratos adultos, apresentando potencial anticoagulante. Além disso, as sericinas de Bragança e Castelo Branco, de 2019, não diferiram muito, contudo foram identificadas diferenças na sua composição de aminoácidos. Por outro lado, a sericina recolhida em Bragança em 2021 e 2022, S3 e S4, respetivamente, apresentou diferenças em relação às outras amostras e apresentou o melhor potencial antiproliferativo, antibacteriano e anticoagulante. Adicionalmente, existem também diferenças entre as amostras extraídas e as comerciais. Palavras-chaveThis work was founded by the project Sericina: um resíduo da indústria da Seda com potencial biomédico (PTDC/BTA-BTA/0696/2020)

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Boas práticas ao Serviço do Utente - Centro Hospitalar do Tâmega e Sousa, EPE

O CHTS pretende e ambiciona na literacia em saúde, na vertente do cidadão, que haja mais igualdades em saúde e que, este cidadão perante a necessidade de tomar decisões de forma autónoma (muitas vezes de elevada complexidade), sobre a promoção de saúde, prevenção das doenças ou seu tratamento, esteja informado e com conhecimentos para o fazer. Pretende que o cidadão seja capaz de obter melhor acesso aos cuidados de saúde, usar e usufruir da forma mais adequada e, de forma intencional e consciente, possa obter os maiores benefíciospara a manutenção do seu estado de saúde. A OMS, define Literacia em Saúde como “o grau em que os indivíduos têm a capacidade de obter, processar e entender as informações básicas de saúde para utilizarem os serviços e tomarem decisões adequadas de saúde”, ou seja, a literacia em saúde contempla um conjunto de conhecimentos, atitudes, habilidades e até competências que capacitam a pessoa no acesso, compreensão das informações para que possa avaliar de forma critica a sua relevância no uso responsável desse conhecimento. Foi, neste contexto, que surgiu no CHTS uma nova ótica de leitura e de intervenção das suas equipas multidisciplinares, na consecução de projetos e ações que visam reforçar os níveis de literacia, de forma multidimensional e colaborativa, aproximando-se cada vez mais da centralidade no cidadão, bem como de uma maior eficiência e eficácia dos serviços, qualidade assistencial e satisfação do cidadão e profissional. Deve-se muito à capacidade dos profissionais de saúde, mesmo com diferenças de uns para outros, em identificar as necessidades das pessoas, em estarem disponíveis para promover mudança, a avaliar diariamente o nível de compreensão, capacidades para realizar tarefas prescritas, motivação e nível de mudança comportamental do cidadão, tendo em conta a sua idade e o seu estado de saúde. José Ribeiro Nunes, Enf. Diretor, Prefácioinfo:eu-repo/semantics/publishedVersio

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).publishersversionpublishe

Portuguese guide lines for the use of biological agents in rheumatoid arthritis - october 2011 update

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 des pite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regi -mens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2,without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opi -nion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituxi mab or tocilizumab).publishersversionpublishe

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics