Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Chemical composition and antifungal activity of the essential oil from the Hymenaea stigonocarpa Mart. Ex Hayne (jatobá-do-cerrado) fruit peel.

This study investigated the chemical composition and the antifungal activity of the essential oil extracted from the Hymenaea stigonocarpa fruit peel (HSFPEO) against Botrytis cinerea, Sclerotinia sclerotiorum, Aspergillus flavus and Colletotrichum truncatum. The HSFPEO obtained through hydrodistillation was analyzed with gas chromatography coupled to mass spectrometry. The antifungal activity was determined by the mean mycelial growth inhibition of the fungus treated with essential oils and growth control. The major constituents of HSFPEO were spathulenol (25.19%) and caryophyllene oxide (13.33%). HSFPEO demonstrated antifungal activity against all fungi tested in all concentrations evaluated in a dose-dependent behavior. The best results were observed against B. cinerea and A. flavus, in which the lowest concentration tested inhibited more than 70% of mycelial growth. Based on the current knowledge, this study describes for the first time the chemical composition and the antifungal activity of HSFPEO against the phytopathogenic fungi B. cinerea and C. truncatum.

Limonoids and insecticidal activity on Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) of Trichilia catigua A. Juss. (Meliaceae).

The aim of the study was to evaluate the effects of the seeds, exocarp and aril extracts from Trichilia catigua A. Juss. (Meliaceae) against Spodoptera frugiperda and present the phytochemical study carried out with the aril extract of T. catigua. Limonoids were isolated from the aril of T. catigua through chromatographic techniques and their structures were proposed by spectroscopic analysis and comparison with literature data. The effects of the seeds, exocarp and aril extracts from T. catigua against S. frugiperda were evaluated considering as parameters the duration and mortality of the larval phase, in addition to the pupal weight. Phytochemical investigation of the aril extracts of T. catigua has led to the identification of the limonoids 6α-O-acetyl-7-deacetyl-14,15-dihydro-15-oxo-nimocinol (1), cedrelone (2) and 6α-O-acetyl-7-deacetylnimocinol (3). The hexane and CH2Cl2 extracts of the aril showed a high rate of larval mortality (100 and 90%, respectively). In addition, a prolongation of larval phase and a reduction in the pupal weight were observed for insects treated with hexane, CH2Cl2 and methanol extracts of seeds and with CH2Cl2 extract of exocarp of T. catigua.

The interplay between HPV, other Sexually Transmissible Infections and genital microbiome on cervical microenvironment (MicroCervixHPV study).

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

Consumo de antibióticos em regime ambulatório: panorama português 2015-2018

A resistência a antibióticos torna-se cada vez mais um problema preocupante em matéria de saúde pública. O elevado consumo de antibióticos para fins terapêuticos e profiláticos, nomeadamente quando usados inadequadamente, é um dos fatores que mais promove a resistência a agentes antimicrobianos. O presente trabalho tem por objetivo analisar a evolução do consumo de antibióticos em Portugal continental estimado a partir da prescrição médica e é expresso em DDD, forma agrupada por região, com destaque para alguns distritos, entre 2015 e 2018. Trata-se de um estudo observacional e descritivo que tem por base dados da Autoridade Nacional do Medicamento e Produtos de Saúde, I.P (Infarmed). Como principais resultados se verificou que o consumo total de antibióticos no período 2015-2018 variou entre 71.613.882,21 DDD e 73.143.461,37 DDD, o que representa um crescimento de a 2,1%, crescendo assim o uso de beta-lactâmicos (J01C), sulfonamidas (J01E), macrólidos (J01F), aminoglicosídeos (J01G) e outras antibactérias (J01X). Destaca-se ainda uma grande redução do uso de quinolonas (J01M) com -18% e uma redução mais discreta das tetraciclinas (J01A) em 3,1%. Como principais conclusões verificou-se um aumento do uso de antibióticos no ambulatório em Portugal com um pico de consumo que alcançou 75.660.771,43 DDD em 2017. No ano seguinte registou-se uma redução do consumo em 3,3%, dando sinais de uma trajetória descendente. Contudo, o valor em 2018 apesar da redução é ainda elevado, sendo por isso necessário reforçar a promoção do uso racional dos antibióticos junto dos utentes e de cada médico prescritor.

Concomitant Nitrofurantoin-Induced Autoimmune Hepatitis and Interstitial Lung Disease.

Antibiotics are known to cause adverse reactions, but multiple organ involvement associated with nonspecific symptoms can lead to a delay in diagnosis. A definitive correlation between each toxin and its effects is difficult to establish due to concomitant potential toxins in the circulation. This article highlights an uncommon case of concomitant nitrofurantoin-induced autoimmune hepatitis and lung fibrosis that fulfills the definitive clinical criteria for diagnosis, presenting histological, imagiological, and immunological evidence of nitrofurantoin-induced toxicity. It occurred in a 68-year-old woman with extended nitrofurantoin intake for urinary tract infection prophylaxis who presented with progressive exercise dyspnea and jaundice. Similar published cases are also reviewed in this article.

Os antibióticos são causas conhecidas de reações adversas, mas o envolvimento multiorgânico associado à sintomatologia inespecífica pode conduzir ao atraso diagnóstico. Devido às potenciais toxinas concomitantemente em circulação, é muitas vezes difícil estabelecer uma correlação definitiva entre cada toxina e os seus efeitos.Este artigo salienta um caso incomum de hepatite autoimune e fibrose pulmonar induzidas pela nitrofurantoína e que cumpre critérios definitivos de diagnóstico, apresentando-se dados histológicos, imagiológicos e imunológicos da toxicidade induzida pela nitrofurantoína.O caso ocorre numa mulher de 68 anos de idade, com toma prolongada de nitrofurantoína como profilaxia de infeção urinária, e que se apresenta com dispneia de esforço progressiva e icterícia. O artigo faz ainda uma revisão de casos semelhantes publicados.

Insecticidal activity of copper (II) complexes with flavanone derivatives.

In this work, we describe the insecticidal activity against Spodoptera frugiperda of flavanone derivatives (naringin, naringenin and hesperidin) complexed to copper (II). For the assays, the compounds were incorporated into an artificial diet and offered to S. frugiperda during its larval period. The duration of larval and pupal phases, the weight of pupae and the percentage of dead insects at the end of the larval phase were evaluated. Among the tested compounds, the free flavanones 1 and 3 and the complexes 4 and 6 showed a shortening of the larval phase when compared to the control. Complex 9 showed the highest toxicity, with 96.66% larval mortality. This is the first report on the insecticidal activity of the Cu2+ complexes of the flavanones naringin, naringenin and hesperidin.[Formula: see text].

Aplicação de terapia por pressão negativa adaptada em lesão por queimadura no norte do Brasil: Relato de caso / Application of low cost negative pressure therapy in burn injury in northern Brazil: Case report

OBJETIVO: Relatar um caso clínico ocorrido em um Centro de Referência de Tratamento de Queimados, submetido a terapia por pressão negativa (TPN) adaptada com materiais hospitalares durante o período de internação, visando a cicatrização mais eficaz da lesão. RELATO DE CASO: Paciente de 47 anos de idade, sexo masculino, vítima de queimadura por descarga elétrica, apresentando lesão em pé direito, região submetida há 16 dias de tratamento por TPN adaptada, tendo como resultado a cicatrização da lesão sem necessidade de enxertia. CONSIDERAÇÕES FINAIS: A aplicação de TPN adaptada demonstrou ser um importante alicerce na cicatrização da lesão, permitindo como resultados a redução da planimetria da lesão, aumento do tecido de granulação, redução do esfacelo, além da aproximação das bordas.

OBJECTIVE: To report a clinical case that occurred in Reference Center for Burn Treatment, submitted to negative pressure therapy (NPT) adapted with hospital materials during the period of hospitalization, aiming at a more effective wound healing. CASE REPORT: 47-year-old male patient, victim of burns caused by electrical discharge, presenting a lesion in the right foot, region submitted to 16 days of treatment with adapted NPT, resulting in healing of the lesion without the need for grafting. FINAL CONSIDERATIONS: the application of adapted not proved to be an important foundation in the healing of the lesion, resulting in a reduction in the planimetry of the lesion, an increase in granulation tissue, a reduction in slough, in addition to approximation of the edges.

Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression.

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

Mortality predictive factors of people living with human immunodeficiency virus and bloodstream infection.

INTRODUCTION: Portugal has one of the highest mortality rates for people living with HIV (PLWHIV) in Europe. After antiretroviral therapy introduction, HIV-associated mortality declined, included the one associated with bloodstream infection (BSI). However it is still high, and European data are scarce . Therefore, characterizing BSI and defining prognostic factors may improve our approach. METHODS: This was a 10-year retrospective study of predictive factors for 30-day and 3-year mortality in PLWHIV with BSI in a tertiary infectious diseases ward. RESULTS: Of 2134 PLWHIV admissions, 145 (6.8%) had a BSI, mostly respiratory and catheter-related bacteremia and globally community-acquired. Nosocomial infections occurred in 42 (36%) cases, mostly caused by Enterococcus spp, Staphylococcus aureus, and Candida spp. PLWHIV with a BSI had higher 30-day mortality (27%) compared to those without a BSI (14%). APACHE II score, corticotherapy, and current intravenous drug use (IDU) had a prognostic impact on 30-day mortality. Three-year survival was 54% in PLWHIV with a BSI; a CD4 <200 cells, vascular or chronic pulmonary disease, and lymphoma were prognostic factors. CONCLUSIONS: Patients with a BSI were more likely to present advanced HIV disease, have more comorbidities, a longer length of stay, and higher 30-day mortality. IDU and severity of infection determined the short-term prognosis. Three-year mortality was primarily influenced by lower CD4 cell counts, hematological tumor, and cardiopulmonary comorbidities. Systemic corticotherapy may influence nosocomial BSI and short-term prognosis.

Skeletal Muscle-Adipose Tissue-Tumor Axis: Molecular Mechanisms Linking Exercise Training in Prostate Cancer.

Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- and adipokines. Together, myokines and adipokines may act in an endocrine-like manner to favor communication between skeletal muscle and WAT, as they may work together to improve whole-body metabolic health. This crosstalk may constitute a potential mechanism by which ET exerts its beneficial role in the prevention and treatment of PCa-related disorders; however, this has not yet been explored. Therefore, we reviewed the current evidence on the effects of skeletal muscle-WAT-tumor crosstalk in PCa, and the potential mediators of this process to provide a better understanding of underlying ET-related mechanisms in cancer.

Association of Aquaporin-3, Aquaporin-7, NOS3 and CYBA polymorphisms with hypertensive disorders in women.

Preeclampsia (PE), a pregnancy disorder influenced by oxidative stress and hypoxia, affects the health of the mother and baby and is associated with an increased risk of future hypertension (HT). Aquaporins are a family of water channels, comprising members that also transport glycerol (aquaglyceroporins) and hydrogen peroxide (peroxiporins), key molecules for metabolic homeostasis and redox signaling. Here, we investigated the association of Aquaporin-3 (AQP3; rs2231231), Aquaporin-7 (AQP7; rs2989924), NOS3 (4B/A intron) and CYBA (rs4673) genetic polymorphisms with the development of hypertensive disorders by qPCR/PCR in a cohort of 150 normotensive (NT) women (N = 90) or with previous PE (N = 60) during pregnancy. Prospectively, women were reclassified 2-16 years after pregnancy as NT (N = 98) or hypertensive (N = 48) and the genetic associations were reevaluated. In addition, genetic associations were reevaluated and compared between normotensive and hypertensive (HT) subjects. We found that AQP3 rs2231231, an aquaglyceroporin/peroxiporin, is associated with the development of HT, whereas AQP7, NOS3 and CYBA polymorphism did not correlate with PE or future HT. Because AQP3 was associated with hypertension only after pregnancy, its role might be related to later risk factors of hypertension such as metabolic syndrome or oxidative stress.

Potential insecticidal activity of aminonaphthoquinone Mannich bases derived from lawsone and their copper (II) complex derivatives.

The fall armyworm, Spodoptera frugiperda, is a polyphagous pest that causes important damage in different regions of America and mainly affects corn crops in both tropical and subtropical areas. Currently, control relies on both transgenic plants and/or chemical pesticides. In this work, we describe insecticidal activity against the fall armyworm from a series of Mannich bases (1-10), derived from 2-hydroxy-1,4-naphthoquinone (lawsone), substituted benzaldehydes, and two primary amines, and their Cu2+ complexes (11-20). The [Cu(L)2] complexes were more effective in larval mortality compared to the free Mannich bases. Among the tested compounds, complex 11 showed the highest toxicity, with 70.00% larval mortality.

Impact of combined training with different exercise intensities on inflammatory and lipid markers in type 2 diabetes: a secondary analysis from a 1-year randomized controlled trial.

BACKGROUND: Exercise is a well-accepted strategy to improve lipid and inflammatory profile in individuals with type 2 diabetes (T2DM). However, the exercise intensity having the most benefits on lipids and inflammatory markers in patients with T2DM remains unclear. We aimed to analyse the impact of a 1-year combined high-intensity interval training (HIIT) with resistance training (RT), and a moderate continuous training (MCT) with RT on inflammatory and lipid profile in individuals with T2DM. METHODS: Individuals with T2DM (n = 80, aged 59 years) performed a 1-year randomized controlled trial and were randomized into three groups (control, n = 27; HIIT with RT, n = 25; MCT with RT, n = 28). Exercise sessions were supervised with a frequency of 3 days per week. Inflammatory and lipid profiles were measured at baseline and at 1-year follow-up. Changes in inflammatory and lipid markers were assessed using generalized estimating equations. RESULTS: After adjusting for sex, age and baseline moderate-to-vigorous physical activity (MVPA), we observed a time-by-group interaction for Interleukin-6 (IL-6) in both the MCT with RT (ß = - 0.70, p = 0.034) and HIIT with RT (ß = - 0.62, p = 0.049) groups, whereas, only the HIIT with RT group improved total cholesterol (ß = - 0.03, p = 0.045) and LDL-C (ß = - 0.03, p = 0.034), when compared to control. No effect was observed for C-reactive protein (CRP), cortisol, tumour necrosis factor-α (TNF-α), soluble form of the haptoglobin-hemoglobin receptor CD163 (sCD163), triglycerides and HDL-C in both groups (p > 0.05). CONCLUSIONS: Favorable adaptations on IL-6 were observed in both the HIIT and MCT combined with RT groups following a long-term 1-year exercise intervention in individuals with T2DM. However, only the HIIT with RT prevented further derangement of total cholesterol and LDL-C, when compared to the control group. Therefore, in order to encourage exercise participation and improve inflammatory profile, either exercise protocols may be prescribed, however, HIIT with RT may have further benefits on the lipid profile. Trial registration Clinicaltrials.gov ID: NCT03144505.

Organização do trabalho na atenção primária à saúde: a experiência em uma região do interior de Portugal / Organization of work in primary health care: the experience in a region of the interior of Portugal

A atenção primária e a resposta em saúde pública, em Portugal, dada a limitação de recursos, encontra ­ se muito dependente do modelo de organização de trabalho das equipes de saúde. No presente estudo, foi realizada uma pesquisa avaliativa, de abordagem qualitativa, com um desenho de estudo de caso para analisar a organização do trabalho numa região do interior de Portugal. A coleta de dados realizou - se com recurso à análise documental, à observação directa e à realização de entrevistas semiestruturadas aplicadas a 96 participantes (gestores, profissionais e usuários) da Unidade Local de Saúde de Castelo Branco, localizada no interior de Portugal. Para interpretação dos dados coletados pelas entrevistas, recorreu ­ se à técnica de análise de conteúdo. Como principais resultados, os usuários relataram dificuldades de comunicação com os funcionários e segundo os profissionais ficou claro as necessárias mudanças na organização, reforço de recursos e definição de metas a atingir para cumprimento de um plano de ação. Em conclusão, a prestação de cuidados na atenção primária à saúde tem uma elevada cobertura de acesso. Porém, mesmo com uma avaliada global positiva por parte dos profissionais, gestores e usuários existem muitas melhorias a implementar, desde a organização do trabalho interno e a articulação com o hospital.

Primary care and public health response in Portugal, given the limited resources, is very dependent on the work organization model of the health teams. In the present study, an evaluation study was carried out, with a qualitative approach, with a case study design to analyze the organization of work in a region of the interior of Portugal. Data collection was carried out using documentary analysis, direct observation and semi- structured interviews applied to 96 participants (managers, professionals and users) of the Local Health Unit of Castelo Branco, located in the interior of Portugal. To interpret the data collected by the interviews, we used the technique of content analysis. As main results, users reported difficulties communicating with employees and according to professionals it was clear the necessary changes in the organization, reinforcement of resources and definition of goals to be reached to fulfill a plan of action. In conclusion, the provision of care in primary health care has high access coverage. However, even with a positive overall assessment by professionals, managers and users there are many improvements to be implemented, from the organization of internal work and articulation with the hospital.

Impact on Longevity of Genetic Cardiovascular Risk and Lifestyle including Red Meat Consumption.

BACKGROUND: Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk. OBJECTIVES: The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity. METHODS: A case-control study involving 521 both gender individuals, 253 centenarians (100.26 ± 1.98 years), and 268 controls (67.51 ± 3.25 years), low (LCR, n = 107) and high (HCR, n = 161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994, AGT-rs4762, AGR1-rs5182, GRK4-rs2960306, GRK4-rs1024323, NOS3-rs1799983, and SLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®. RESULTS: Antilongevity factors consisted (OR 95% CI, p < 0.05) BMI 1.558 (1.445-1.680), hypertension 2.358 (1.565-3.553), smoking habits 4.528 (2.579-7.949), diabetes 5.553 (2.889-10.675), hypercholesterolemia 1.016 (1.010-1.022), and regular consumption of red meat 22.363 (13.987-35.755). Genetic aspects particularly for HCR individuals ACE II (OR: 3.96 (1.83-8.56), p < 0.0001) and NOS3 TT (OR: 3.11 (1.70-5.70), p < 0.0001) genotypes were also risk associate. Obesity, smoking, hypercholesterolemia, and frequent consumption of red meat have an additive action to hypertension in the longevity process. There was a synergistic interaction between the endothelial NOS3 genotypes and the severity of arterial hypertension. An epistatic interaction between functional genetic variants of GRK4 and angiotensinogen was also observed. CONCLUSIONS: Cardiovascular risk-related genetic and multifactorial or predominantly lifestyle aspects and its interactions might influence the aging process and contribute to exceptional longevity in Portuguese centenarians. Besides lifestyle, the activity of nitrite oxide synthase may be one of the main physiologic regulators of cardiovascular protection in the path of longevity.

Gestão hospitalar em Portugal: a busca de um modelo ajustado aos hospitais públicos / Hospital management in Portugal: search the best model to public hospitals

A busca de um modelo de gestão hospitalar adequado à prestação de cuidados de saúde no setor público é já procurado em Portugal há várias décadas. Foram implementados vários modelos e realizadas avaliações quantitativas, ouvindo poucas vezes os intervenientes nos processos. Objetivo: o presente estudo objetivou analisar as percepções dos grupos de interesse (stakeholders) relativamente às medidas aplicadas que mais contribuíram para a consecução dos objetivos da reforma para a melhoria do acesso, qualidade e eficiência. Método: estudo exploratório-descritivo, de abordagem qualitativa, realizado com recurso a 50 entrevistas semiestruturadas gravadas e transcritas, optando-se pela análise de conteúdo. Resultados: as falas indicam que os diferentes grupos têm diferentes interpretações, dependendo da sua atividade ou função no sistema de saúde. Todos referem que a gestão melhorou com a implementação de práticas de gestão empresarial e com a prestação regular de contas. No entanto, exigem mais transparência, incentivos e acesso. Conclusões: A inovação nas práticas de gestão hospitalar contribuiu para a melhoria do acesso, da qualidade e eficiência.

The search for a model of hospital health for public health care has been sought in Portugal for decades. Several models were implemented and met the quantitative needs, and sometimes they were implemented in the processes. Objective: This study aimed to analyze the perceptions of the stakeholders on the measures that contributed most to the achievement of the objectives of the reform in order to improve access, quality and efficiency. Method: na exploratory­descriptive study, with a qualitative approach, performed with a 50 semi­structured interviews recorded and transcribed, opting for content analysis. Results: the speeches indicate that the different groups have different interpretations, depending on their activity or function in the health system. All said that it is beer to implement business and financial management practices. However, call for more transparency, incentives and access. Conclusions: Innovation in hospital management practices built to improve access, quality and efficacy.

Orbital Plasmacytoma, An Uncommon Presentation of Advanced Multiple Myeloma.

INTRODUCTION: Extramedullary plasmacytomas are present in 13% of multiple myeloma (MM) patients. Less than 5% of MM cases are non-secretory. The orbital location is uncommon and a minority of orbital tumours are plasmacytomas. DESCRIPTION: The patient was a 71-year-old man, with right proptosis, retro-ocular pain and epistaxis with visual acuity 2/10, limitation of upper eye movement and scattered ecchymosis. Blood tests revealed severe anaemia, coagulopathy, increased serum creatinine, LDH and C-RP without improvement after antimicrobial treatment. Peripheral immunophenotyping showed 9.4% of plasma cells with intracytoplasmic clonal κ chains. IgG and λ chains were decreased with normal plasma and urine immunofixation. Orbital CT: retro-orbital superomedial tumour with bone destruction. Histology of the tumour and bone biopsy was consistent with plasmacytoma. The patient was deceased in 2 weeks. DISCUSSION: MM accounts for 10% of haematopoietic tumours; 7% of cases present with plasmacytomas at diagnosis. Orbital locations are rarely reported (frequently in the temporal region). Proptosis, ptosis and reduced visual acuity are common symptoms. However, orbital pain is less frequent. Most cases of MM demonstrate hypergammaglobulinaemia. Only 5% of MM cases are non-secretory.The uncommon location, topography, symptom peculiarities and absence of monoclonality led to the diagnostic challenge of this fatal case of MM. LEARNING POINTS: Multiple myeloma (MM) represents 10% of malignant haematologic disease, 13% of which presents plasmacytomas (mostly in the axial skeleton).Orbital plasmacytoma is an uncommon presentation of MM and only 1% of orbital tumours are plasmacytomas. Proptosis is the most common symptom.Although the majority of MM cases demonstrate hypergammaglobulinaemia, non-secretory MM is described as constituting less than 5% of cases.

The Portuguese generic medicines market: What's next?

Brand-name medicines have dominated the Portuguese market for several decades with unquestionable exclusivity. This resulted particularly from the absence of a requirement of prescriptions by international non-proprietary name. To promote the enhancement of both efficiency and sustainability in the health system, the Portuguese government introduced the generics in Portugal by the 90 s. However, only in the first decade of the 21st century were some policies implemented to increase their market share. Although some expectations were created, the use of generics has increased moderately during that period, in which policies to promote them were consolidated by imposing the austerity principles in the midst of the economic and social crisis. This study analyses the main policy measures already implemented as well as the incentives created for the replacement of brand-name medicines with generics. In addition, the present study also makes some recommendations to promote a broader and better use of generics in Portugal.