Logistics in the health sector

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and EconomicsThis project aims to analyse a hospital’s logistic processes and to find strategies to improve it’s efficacy. As a result of the literature review and the study of Faro Hospital’s practices, it was possible to make some proposals, leading to a more efficient use of the resources. Consignment contracts with the suppliers, to use an existent hangar as the unique consumption materials’ warehouse, employ inventory management techniques widely used in other industries and create advanced warehouses inside the main hospital departments, are the key recommendations of this project. These ideas can be applied to other hospitals, helping to reduce costs and improve levels of quality in the health sector

Characterization of the clinical, histological and genetic profile of articular damage in hereditary hemochromatosis

RESUMO: A osteoartrose (OA) é a patologia articular mais frequente nos humanos. Afecta a articulação como um todo e as suas características principais são a destruição progressiva da superfície articular, a remodelação anormal do osso subcondral, a formação de osteofitos, o enfraquecimento das estruturas ligamentares, a atrofia muscular e, em alguns casos, a inflamação da membrana sinovial. Todas estas alterações levam a uma articulação dolorosa e incapaz de cumprir a sua função. Existem vários factores que aumentam o risco de vir a desenvolver OA mas a sequência exacta de acontecimentos que levam à destruição de uma articulação ainda não está totalmente esclarecida. A Hemocromatose Hereditária (HH) é uma doença causada por mutações no gene HFE e caracteriza-se por causar uma sobrecarga sistémica de ferro e acumulação tóxica de ferro nas células parenquimatosas do fígado, do coração e das glândulas endócrinas. Está também associada a uma maior prevalência de patologias do aparelho osteoarticular, nomeadamente OA. Ainda não está definido qual o papel que a sobrecarga de ferro desempenha na génese da OA secundária à HH. Para melhor entender os mecanismos moleculares responsáveis pelo aparecimento da OA secundária à HH, no decorrer do presente trabalho, foi induzida cirurgicamente OA no joelho de um modelo murino de hemocromatose e foram estudadas as alterações verificadas ao nível da cartilagem articular e do osso. Para além disso, para perceber se as diferentes mutações no gene HFE influenciavam a sobrecarga sistémica de ferro e as complicações osteoarticulares desta doença, foi estudada a prevalência de patologia osteoarticular em coortes de doentes com diferentes genótipos de HH. Os ratinhos Hfe-KO apresentaram uma sobrecarga sistémica de ferro e uma deposição aumentada de ferro na membrana sinovial do joelho após a cirurgia. Às 8 semanas após cirurgia os ratinhos Hfe-KO apresentavam uma pontuação histológica da OA significativamente superior aos seus controlos saudáveis, traduzindo-se numa maior degeneração da cartilagem articular. Utilizando um aparelho de microtomografia computorizada foi possível estudar as alterações do osso subcondral ao nível da tíbia proximal. Esta apresentava-se com um volume ósseo aumentado e as trabéculas que a constituíam eram mais espessas do que as do grupo de controlo. Ao nível da expressão genética e imunohistoquímica observámos nos joelhos dos ratinhos Hfe-KO, um aumento significativo da expressão da metaloproteinase da matriz 3. No estudo das coortes de doentes com HH, a maioria dos doentes eram homozigóticos para a mutação C282Y. A concentração de ferritina sérica e a saturação da transferrina sérica na altura do diagnóstico eram significativamente mais altas no grupo dos doentes homozigóticos quando comparadas com a dos doentes heterozigóticos compostos (C282Y/H63D). Para além disso os doentes homozigóticos para a mutação C282Y referiam uma maior prevalência de complicações osteoarticulares. Os resultados deste estudo sugerem que a sobrecarga sistémica de ferro não é uma causa direta de OA mas sim um factor que aumenta a vulnerabilidade das articulações à sobrecarga mecânica. Supõe-se que a sobrecarga de ferro a nível sistémico e sinovial aumenta a resposta catabólica da cartilagem articular ao stress mecânico, acelerando o processo patológico da osteoartrose. Os dados obtidos sugerem ainda que a prevalência de complicações osteoarticulares na HH está relacionada com a magnitude da sobrecarga de ferro, uma vez que observámos uma maior prevalência de OA nos doentes homozigotos para a mutação C282Y, um genótipo associado a uma maior sobrecarga sistémica de ferro.ABSTRACT: Osteoarthritis (OA) is the most common joint disease in humans. It affects the joint as a whole and is characterized by progressive articular cartilage destruction, abnormal subchondral bone remodelling, formation of osteophytes, ligament and periarticular muscle weakening and in some cases synovial inflammation, which ultimately lead to a painful and impaired joint. There are several known risk factors for the development of OA but the exact sequence of events that lead to the destruction of the articular cartilage is not yet fully understood. Hereditary hemochromatosis (HH), a disease caused by mutations in the HFE gene, is characterised by systemic iron overload, toxic accumulation of iron in parenchymal cells of liver, heart, and endocrine glands. It is also associated with musculoskeletal complications, namely an increased prevalence of OA. The role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved in the pathology of HHrelated OA, we surgically induced OA in the knee of a murine model of hereditary hemochromatosis and studied the changes to cartilage and bone. Also, in order to understand how the different mutations in the HFE gene affect systemic iron overload and related musculoskeletal complications, we studied the prevalence of musculoskeletal complications in a cohort of patients with different HH genotypes. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro-CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. Among our cohort of HH patients the majority were homozygous for the C282Y mutation. The serum ferritin concentration and serum transferrin saturation at diagnosis were significantly higher in C282Y homozygous patients compared with those who were compound heterozygous (C282Y/H63D). Also the overall prevalence of self-reported musculoskeletal complications was significantly higher in patients with C282Y homozygosity. The findings of this study suggest that systemic iron overload does not cause OA directly but acts as a susceptibility factor. The systemic and synovial iron overload both contribute to increase the catabolic response of the articular cartilage to mechanical also suggests that the prevalence of musculoskeletal complications of HH is related to the magnitude of the iron overload, since there was a greater prevalence of OA in the homozygotes for the C282Y mutation, a genotype associated with higher systemic iron overload

Os militares portugueses na Guiné- Bissau: da contestação à descolonização

A 25 de Abril de 1974, Portugal despertava com um golpe militar, depois de um longo período de regime ditatorial, iniciado a 28 de Maio de 1926 e fossilizado sob a forma do Estado Novo. Os militares revoltosos decidiram tomar o poder com vista à mudança do paradigma governativo vigente, que persistia no arrastamento de uma guerra no Ultramar dividida em três frente distintas – Guiné, Angola e Moçambique – e sem fim aparente. Com efeito, a ruptura que se verificou em Portugal proporcionou o começo da etapa final do processo de Descolonização, que conhecera o seu princípio, em 1961, com o despontar das lutas nacionalistas armadas nas colónias portuguesas. A transferência de poderes e de soberania, nas colónias, para os movimentos nacionalistas foi um desígnio assumido pela elite governativa que se estabeleceu após o 25 de Abril de 1974, dando origem ao processo mais marcante da história contemporânea portuguesa, que culminou no fim do domínio português sobre vastos territórios africanos. O presente trabalho é fruto de uma investigação que procurou averiguar como se desenvolveu, numa dessas colónias – a Guiné -, um núcleo de militares contestatários e, posteriormente, conspirativos, cuja acção viria a derrubar governo, e a forma como, consumado esse derrube, foi conduzido o respectivo processo de transferência de poder para uma entidade política previamente existente e internacionalmente reconhecida – a República da Guiné-Bissau. Assim, ficou claro quando é que o processo conspirativo se iniciou na Guiné, que os processos negociais se deram à escala local entre militares do MFA e do movimento nacionalista PAIGC, que originaram um processo de retirada das forças portuguesas bastante célere, sem interferências do poder político português e que, como consequências mais visíveis, acabaram por impedir a pluralidade partidária na Guiné-Bissau e não salvaguardaram muitos dos que, combatendo por Portugal, permaneceram aquele território.On April the 25th, 1974, Portugal awoke in a military coup after a long period of dictatorship which began in May the 28th, 1926, and fossilized in the form of Estado Novo (New State). The military insurgents decided to seize power in order to change the existing government frame that persisted in dragging a war overseas in three different fronts - Guinea, Angola and Mozambique - with no end in sight. Indeed, the coup d’état that occurred in Portugal began the final stage of the decolonization process which had started in 1961 with the beginning of the armed nationalist struggle in the Portuguese colonies. The transfer of powers and sovereignty in the colonies for the nationalist movements was a plan made by the governing elite established after April 25, 1974, giving rise to the most significant process of the contemporary Portuguese history – the end of the Portuguese ruling over vast territories in Africa. This work is the result of an investigation that sought to ascertain how a core of disaffected military developed in a particular colony - Guinea –, overthrowing the government and how the new portuguese military and political elite led the process of transferring power to a political entity that already existed and was internationally recognized - the Republic of Guinea-Bissau. It became clear when the Portuguese military began plotting against the regime, how the negotiating process was conducted at a local dimension almost without Lisbon’s interference and how it originated a quick withdraw of the Portuguese forces that did not provide protection neither to political parties other than PAIGC nor to those who fought by the portuguese side and remained in Guinea-Bissau after the portuguese retreat

Effect of C282Y genotype on self-reported musculoskeletal complications in hereditary hemochromatosis

Objective Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. Methods A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. Results In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) mu g/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). Conclusion Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.Association Rhumatisme et Travail (Centre Viggo Petersen, Hospital Lariboisiere, Paris

On mining protein unfolding simulation data with inductive logic programming

The detailed study of folding and unfolding events in proteins is becoming central to develop rational therapeutic strategies against maladies such asAlzheimer and Parkinson disease. A promising approach to study the unfolding processes of proteins is through computer simulations. However, these computer simulations generate huge amounts of data that require computational methods for their analysis.In this paper we report on the use of Inductive Logic Programming (ILP) techniques to analyse the trajectories of protein unfolding simulations. The paper describes ongoing work on one of several problems of interest in the protein unfolding setting. The problem we address here is that of explaining what makes secondary structure elements to break down during the unfolding process. We tackle such problem collecting examples of contexts where secondary structures break and (automatically) constructing rules that may be used to suggest the explanations

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Funding Information: This project was partially supported by an IDI&CA grant IPL/2021/DiffMeDiME_ESTeSL by H&TRC- Health & Technology Research Center, ESTeSL- Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa and by Retina Institute of Lisbon (IRL).Purpose: DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. Methods: A total of 27 diabetic patients, aged 59–90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. Results: The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = −0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = −0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = −0.815; p = 0.007) with HbA1c and RNFL (r = −0.664; p = 0.026) in CG. Conclusions: Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.publishersversionepub_ahead_of_prin

Role of DNA methylation in persistent diabetic macular edema

Projeto ID&CA 2021_IPL/2021/DiffMeDiME_ESTeSLBackground: a) Disease duration and metabolic control are insufficient to understand Diabetic Macular Edema (DME), the leading cause of vision loss in people with diabetes; b) 30-40% of cases of DME do not respond optimally to AVEGF (loading phase); c) poor genetic association in DR development (<25% RD) and PDR progression (25-50%). Purpose: To study the role of DNA methyltransferase expression (DNMT1,DNMT3a, DNMT3b) in persistent diabetic macular edema.info:eu-repo/semantics/publishedVersio

New occurrence of B chromosomes in Partamonahelleri (Friese, 1900) (Hymenoptera, Meliponini)

Cytogenetic analyses of the stingless bee Partamona helleri collected in the state of Bahia, Northeast Brazil revealed the chromosome numbers n = 18 in the haploid males and 2n = 35 in the diploid females. All karyotypes displayed one large acrocentric B chromosome, which differs from the minute B chromosomes previously described in the populations from southeastern Brazil. Giemsa staining, C-banding and DAPI/CMA3 fluorochrome staining also revealed a remarkable interpopulational divergence regarding both the regular karyotype and the B chromosomes. The B chromosomes found in the samples from Jequié, Bahia, were entirely heterochromatic, while those found in Cravolândia, Bahia, displayed a euchromatic portion at the telomeric end of the long arm. CMA 3 labeling sites varied from seven to eight between the two localities in Bahia, due to the presence of an extra GC-rich block in the karyotype of the samples from Jequié. This is the first report of a large B chromosome in P. helleri and reveals the occurrence of a geographic differentiation within this species

Cytogenetic characterization of Partamona cupira (Hymenoptera, Apidae) by fluorochromes

Four colonies of the stingless bee Partamona cupira (Hymenoptera: Apidae) were cytogenetically analyzed using conventional staining and the fluorochromes CMA3 e DAPI. The females have 2n = 34 chromosomes (2K = 32 M¯+2 A¯). Some females, however, presented an additional large B acrocentric chromosome, to a total of 2n = 35. Chromosome B and the chromosomal pairs 2, 9 and 10 showed CMA 3+ bands, indicating an excess of CG base-pairs. A clear association was verified between the P. helleri B chromosome SCAR marker and the presence of a B chromosome in P. cupira. The data obtained suggests that B chromosomes in P. helleri and P. cupira share a common origin