Ocular severe involvement in oculofaciocardiodental syndrome: Description of a case series.

BACKGROUND: Oculofaciocardiodental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental, and cardiac systems, being an X-linked condition caused by pathogenic variants in the BCL-6 corepressor gene (BCOR). We report a case series of three female patients with OFCD syndrome with severe glaucoma. RESULTS: Three female patients with OFCD syndrome with different variants involving BCOR gene, in heterozygosity: a seven-years-old girl with an insertion (c.2037_2038dupCT), a nine years-old girl with a microdeletion in the X (p21.2-p11.4)) spanning the BCOR gene; and a 25 years-old female with a deletion (c.3858_3859del). Systemic involvement is variable among patients ranging from one patient mainly with ocular and dental involvement to one with associated intra-auricular and intra-ventricular defects. All the patients presented with congenital cataracts diagnosed in the first days of life. Cataract surgery was performed without incidents between 6 and 16 weeks of age in all the patients. Postoperatively, the three patients developed ocular hypertension and glaucoma with the need for surgical interventions, including trabeculectomy, Ahmed valve implantation, and cyclophotocoagulation. CONCLUSION: OFCD syndrome characterizes by a severe ocular involvement with glaucoma as a characteristic feature. Ocular hypertension after cataract surgery in these patients is challenging, almost always needing surgery during childhood. Therefore, we consider BCOR disruption may predispose to a higher incidence of glaucoma due to its aggressiveness and early onset on our case series. The awareness of these complications is crucial to an adequate follow-up of the patients.

Indoor Content Delivery Solution for a Museum Based on BLE Beacons.

The digital transformation advancement enables multiple areas to provide modern services to their users. Culture is one of the areas that can benefit from these advances, more specifically museums, by presenting many benefits and the most emergent technologies to the visitors. This paper presents an indoor location system and content delivery solution, based on Bluetooth Low Energy Beacons, that enable visitors to walk freely inside the museum and receive augmented reality content based on the acquired position, which is done using the Received Signal Strength Indicator (RSSI). The solution presented in this paper was created for the Foz Côa Museum in Portugal and was tested in the real environment. A detailed study was carried out to analyze the RSSI under four different scenarios, and detection tests were carried out that allowed us to measure the accuracy of the room identification, which is needed for proper content delivery. Of the 89 positions tested in the four scenarios, 70% of the received signals were correctly received throughout the entire duration of the tests, 20% were received in an intermittent way, 4% were never detected and 6% of unwanted beacons were detected. The signal detection is fundamental for the correct room identification, which was performed with 96% accuracy. Thus, we verified that this technology is suitable for the proposed solution.

Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review.

INTRODUCTION: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. OBJECTIVE: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. METHODS: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. RESULTS: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. CONCLUSION: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.

Terson Syndrome - Clinical Presentation, Management, and Visual Outcomes in a Tertiary Centre.

Purpose: The purpose of this study was to characterize the clinical presentation, management strategy and visual outcomes of patients diagnosed with Terson syndrome and followed in a tertiary centre in Portugal. Patients and Methods: A single-centre retrospective study was performed, based on the survey review of the medical records of every consecutive patient diagnosed with Terson syndrome and followed from January 2018 to August 2021. The change in best-corrected visual acuity (BCVA) from baseline to the final evaluation was the primary outcome. Results: Fifteen eyes from 8 patients (50% female) were included. The mean age at diagnosis was 55±7 years. The neurological event was traumatic brain injury in 37.5% (n=3) and subarachnoid haemorrhage in 62.5% of the patients (n=5). Bilateral intraocular haemorrhage occurred in 875% (n=7) of the patients. Vitreous and preretinal haemorrhages occurred each in 66.7% (n=10), intraretinal in 30% (n=3) and subretinal in 13.3% (n=2) of the eyes. In 40% of the eyes (n=6), spontaneous resolution of intraocular haemorrhage occurred, while PPV was performed in the remaining 60% (n=9). Ocular haemorrhage detection occurred 58.47 ± 40.94 days after the neurological event (range 11 to 121 days). Baseline BCVA was 1.11 ± 1.01 logMAR and improved to 0.32 ± 0.69 logMAR in the follow-up period (p=0.004). A positive correlation was found between initial and final BCVA (Spearman's rho = 0.643, p=0.01). Baseline BCVA of eyes undergoing PPV was lower than of those conservatively managed (1.84±0.72 vs 0.20±0.28 logMAR, p<0.001). However, there were no statistically significant differences in final BCVA after surgery or observation (0.56 ± 0.90 vs 0.04 ± 0.04 logMAR, p=0.149). Longer periods between the neurological and the ophthalmological diagnosis were correlated with worse final BCVA (Spearman's rho = 0.688, p=0.005). Conclusion: Terson syndrome is a potential cause of irreversible visual loss. Diagnosis delay may affect visual prognosis. PPV is indicated when intraocular haemorrhage is dense and does not resolve spontaneously or when visual acuity at presentation is low, allowing for good visual outcomes with minimal complications.

Intravitreal Fluocinolone Acetonide Implant (FAc, 0.19 mg, ILUVIEN®) in the Treatment of Patients with Recurrent Cystoid Macular Edema After Pars Plana Vitrectomy.

INTRODUCTION: Postoperative cystoid macular edema (PCME) is a complication of several ocular procedures, including pars plana vitrectomy (PPV), due to the activation of the inflammatory cascade. The purpose of this case series is to evaluate the effectiveness and safety of fluocinolone acetonide intravitreal implant (FAc, 0.2 µg/day; ILUVIEN®) in the treatment of refractory PCME after successful PPV. METHODS: This retrospective observational case series includes consecutive eyes of patients with recurrent PCME after PPV and treated with a single FAc implant at Centro Hospitalar Universitário de São João, Porto, Portugal. Previous treatments, best-corrected visual acuity (BCVA, ETDRS letters), central macular thickness (CMT, µm), intraocular pressure (IOP, mmHg), and IOP-lowering medication needed were recorded at baseline and during follow-up. Total macular edema resolution was defined as CMT less than 300 µm or a reduction of greater than 20%, and partial macular edema resolution was defined as a reduction of greater than 10%. RESULTS: Nine eyes from nine patients were included. Before FAc implant, all eyes received intravitreal short-action corticosteroids (triamcinolone and dexamethasone implant), with a good response but relapse 1-5 months later. At baseline, BCVA was 55.0 ± 10.6 letters, CMT was 514.9 ± 165.6 µm, and IOP was 15.4 ± 2.4 mmHg with four eyes under IOP-lowering medication. After FAc implant, all eyes achieved edema resolution (eight total and one partial) with a peak gain of 17.2 letters and a maximum decrease of 208.2 µm in CMT. During follow-up (44.0 ± 14.8 months), 66.7% of the eyes kept their macula dry and three showed recurrence after 11, 14, and 28 months, respectively. The maximum IOP registered was 17.0 ± 6.0 mmHg. IOP-lowering regimen was increased in one eye and two additional eyes started hypotensive drops. CONCLUSION: FAc implant can be considered a therapeutic alternative in PCME refractory to other therapies in vitrectomized eyes, reducing the need for repeated treatments.

Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review / Transplante de microbiota fecal e suas repercussões em pacientes com melanoma refratário à terapia anti-PD-1: revisão de escopo

ABSTRACT Introduction: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. Objective: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. Methods: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. Results: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. Conclusion: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.

RESUMO Introdução: apesar de extremamente eficaz em alguns casos, até 70% dos pacientes com melanoma não respondem aos anti-PD-1/PD-L1 (resistência primária) e muitos dos respondedores, eventualmente, acabam progredindo (resistência secundária). Extensos esforços estão sendo realizados para superar esta resistência através de novas estratégias, sobretudo, visando a modulação da microbiota intestinal. Objetivo: avaliar se o transplante de microbiota fecal (TMF), associado à imunoterapia, é benéfico no curso clínico do paciente com melanoma refratário. Métodos: trata-se de uma revisão de escopo, baseada em estudos coletados nas plataformas MEDLINE, ScienceDirect, The Cochrane Library, Embase e BMJ Journals; utilizando os descritores: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; e "Microbiota". Foram incluídos ensaios clínicos, na língua inglesa, com dados relevantes sobre a temática e disponíveis integralmente. Não foi determinado um período de corte temporal, devido à quantidade limitada de evidências sobre o tema. Resultados: o cruzamento dos descritores permitiu a identificação de 342 publicações e, após a aplicação dos critérios de elegibilidade, permitiu a seleção de 4 estudos. A partir das análises, observou-se que grande parte dos estudados superaram a resistência aos inibidores do checkpoint imunológico pós-TMF, com melhor resposta ao tratamento, menor crescimento tumoral e aumento da resposta imunológica benéfica. Conclusão: nota-se que o TMF favorece a resposta do melanoma à imunoterapia, traduzido por benefício clínico significativo. Entretanto, novos estudos são necessários para a completa elucidação das bactérias e mecanismos envolvidos, bem como para que haja a translação das novas evidências para a prática assistencial oncológica.

3'Nucleotidase/nuclease is required for Leishmania infantum clinical isolate susceptibility to miltefosine.

BACKGROUND: Miltefosine treatment failure in visceral leishmaniasis in Brazil has been associated with deletion of the miltefosine susceptibility locus (MSL) in Leishmania infantum. The MSL comprises four genes, 3'-nucleotidase/nucleases (NUC1 and NUC2); helicase-like protein (HLP); and 3,2-trans-enoyl-CoA isomerase (TEI). METHODS: In this study CRISPR-Cas9 was used to either epitope tag or delete NUC1, NUC2, HLP and TEI, to investigate their role in miltefosine resistance mechanisms. Additionally, miltefosine transporter genes and miltefosine-mediated reactive oxygen species homeostasis were assessed in 26 L. infantum clinical isolates. A comparative lipidomic analysis was also performed to investigate the molecular basis of miltefosine resistance. FINDINGS: Deletion of both NUC1, NUC2 from the MSL was associated with a significant decrease in miltefosine susceptibility, which was restored after re-expression. Metabolomic analysis of parasites lacking the MSL or NUC1 and NUC2 identified an increase in the parasite lipid content, including ergosterol; these lipids may contribute to miltefosine resistance by binding the drug in the membrane. Parasites lacking the MSL are more resistant to lipid metabolism perturbation caused by miltefosine and NUC1 and NUC2 are involved in this pathway. Additionally, L. infantum parasites lacking the MSL isolated from patients who relapsed after miltefosine treatment were found to modulate nitric oxide accumulation in host macrophages. INTERPRETATION: Altogether, these data indicate that multifactorial mechanisms are involved in natural resistance to miltefosine in L. infantum and that the absence of the 3'nucleotidase/nuclease genes NUC1 and NUC2 contributes to the phenotype. FUNDING: MRC GCRF and FAPES.

Demand Response Contextual Remuneration of Prosumers with Distributed Storage.

Prosumers are emerging in the power and energy market to provide load flexibility to smooth the use of distributed generation. The volatile behavior increases the production prediction complexity, and the demand side must take a step forward to participate in demand response events triggered by a community manager. If balance is achieved, the participants should be compensated for the discomfort caused. The authors in this paper propose a methodology to optimally manage a community, with a focus on the remuneration of community members for the provided flexibility. Four approaches were compared and evaluated, considering contextual tariffs. The obtained results show that it was possible to improve the fairness of the remuneration, which is an incentive and compensation for the loss of comfort. The single fair remuneration approach was more beneficial to the community manager, since the total remuneration was lower than the remaining approaches (163.81 m.u. in case study 3). From the prosumers' side, considering a clustering method was more advantageous, since higher remuneration was distributed for the flexibility provided (196.27 m.u. in case study 3).

A New Exergy Disaggregation Approach for Complexity Reduction and Dissipative Equipment Isolation in Thermoeconomics.

Thermoeconomics connects thermodynamic and economic concepts in order to provide information not available in conventional energy and economic analysis. Most thermoeconomicists agree that exergy is the most appropriate thermodynamic magnitude to associate with cost. In some applications, exergy disaggregation is required. Despite the improvement in result accuracy, the modeling complexity increases. In recent years, different exergy disaggregation approaches have been proposed, mostly to deal with dissipative components and residues, despite all of them also increasing the complexity of thermoeconomics. This study aims to present a new thermoeconomic approach based on exergy disaggregation, which is able to isolate dissipative components with less modeling complexity. This approach, called the A&F Model, splits the physical exergy into two terms, namely, Helmholtz energy and flow work. These terms were evaluated from a thermoeconomic point of view, through a cost allocation in an ideal Carnot cycle, and they were also applied and compared with the UFS Model, through a cost allocation analysis, in a case study with an organic Rankine cycle-powered vapor compression refrigeration system. The complexity and computational effort reduction in the A&F are significantly less than in the UFS Model. This alternative approach yields consistent results.

Dataset of an energy community's generation and consumption with appliance allocation.

Energy data measured on-site from buildings can help describe the consumption behavior of end-users and can be used to examine and prove certain theorems and models, that require a large volume of data to be gathered. However, the direct extraction of this data can often be a lengthily and costly process. As a result, a dataset of a residential community was constructed based on real data, where sample consumption and photovoltaic generation profiles were attributed to 50 residential households and a public building (municipal library), a total of 51 buildings. In addition, the overall power consumption of these houses was desegregated into the consumption of 10 commonly used appliances using real energy profiles. First, several consumption and photovoltaic generation profiles, as well as a vast collection of appliance profiles, were gathered. These profiles were obtained from household readings in different locations, while the public building's profile was based on the consumption and photovoltaic production profiles of the research building GECAD. The profiles went through the process of normalization and new profiles were generated to complete the number of end-users needed. Moreover, these profiles were given a maximum consumption and production level at random before being accepted by one of the end-users. Therefore, fourteen of these households and the public building were randomly attributed with renewable solar energy. Finally, if possible, the tool created allocated, at random in previously determined intervals, the appliances' load profiles into each end-user's available consumption areas.

Canine rabies in Belford Roxo City, Rio de Janeiro, Brazil: a case report.

Rabies is a highly lethal disease and is considered one of the most important zoonoses worldwide. In Brazil, the rabies cycle in domestic animals is under control. However, there is feedback from the wildlife cycle as many bats are present in the cities and rural areas of the country. This paper reports a case of a dog receiving veterinary assistance that presented with misbehavior and other unusual signs. After clinical evaluation by two veterinarians and a period of hospitalization to perform tests and treatment, the dog died, and the Municipal Health Department was contacted due to the suspicion of rabies. After laboratory testing and sample analysis, the diagnosis of rabies was confirmed. This case demonstrates the importance of veterinarians' qualifications in performing clinical and laboratory diagnoses, such as their knowledge concerning surveillance measures and preventive steps before and after exposure. Reinforcing the significance of maintaining vaccination coverage for rabies and promoting public and private vaccination campaigns in areas that lack vaccination campaigns are useful.

A Raiva é uma doença de elevada letalidade e é considerada uma das mais importantes zoonoses do planeta. Seu ciclo urbano está praticamente controlado no Brasil, porém, é constantemente retroalimentado pelo ciclo silvestre devido à presença de morcegos tanto nas áreas rurais como urbanas. Este trabalho relata o caso de um cão que foi levado para atendimento veterinário apresentando comportamento e outros sinais incomuns. Após a avaliação de dois profissionais veterinários e uma internação para exames e tratamento, o animal foi a óbito e o serviço municipal de saúde foi acionado devido à suspeita de Raiva. Após os devidos exames laboratoriais, a Raiva foi confirmada nas amostras analisadas. Este caso demostrou a importância não só da capacitação dos profissionais veterinários para suspeitar, realizar o diagnóstico clínico e laboratorial da Raiva como o conhecimento acerca das medidas de vigilância, prevenção e controle e os esquemas de profilaxia da raiva humana pré e pós exposição. Ressalta-se ainda a importância da manutenção da cobertura vacinal contra a Raiva, seja ela realizada por campanhas públicas de vacinação, seja por iniciativa dos tutores onde as campanhas não mais ocorrem.

Towards circular economy in the textiles and clothing value chain through blockchain technology and IoT: A review.

The textile and clothing industry sector has today a big environmental impact, not only due to the consumption of water and the use of toxic chemicals but also due to the increasing levels of textile waste. One way to reduce the problem is to circularise the, currently linear, textile and clothing value chain, by using discarded clothes as raw material for the production of new clothes, transforming it into a model of circular economy. This way, while reducing the need to produce new raw materials (e.g. cotton), the problem of textile waste produced is also reduced, thus contributing to a more sustainable industry. In this article, we review the current approaches for traceability in the textile and clothing value chain, and study a set of technologies we deem essential for promoting the circular economy in this value chain - namely, the blockchain technology - for registering activities on traceable items through the value chain, and the Internet of Things (IoT) technology, for easily identifying the traceable items' digital twins.

Recruiting strategic human capital from MNCs-Does hiring MNC managers enable exporting in domestic firms?

Exporting is a central growth strategy for most firms and managers with international experience are instrumental for export decisions. We suggest that such managers can be hired from Multinational Corporations (MNCs). We integrate theory from strategic human capital research into models explaining export decisions. We theorize that hiring managers from MNCs increases the odds of domestic firms to start exporting and this effect depends on the similarities between hiring firms and MNCs. We hypothesize that young firms will benefit comparatively less from hiring MNC managers. In contrast, firms with internationally diverse workforces and with high degrees of hierarchical specialization will benefit the most from hiring MNC managers. We test and support these hypotheses for 474,926 domestic firms in Sweden, which we observe between 2007 and 2015.

The Hummingbird Collection of the Natural History and Science Museum of the University of Porto (MHNC-UP), Portugal.

BACKGROUND: The Hummingbird (Family Trochilidae) Collection of the Natural History and Science Museum of the University of Porto (MHNC-UP) is one of the oldest collections of this family harboured in European museums. Almost 2,000 specimens, that encompass most of the taxonomic diversity of this family, were collected in the late 19th Century. The collection is relevant due its antiquity and because all specimens were bought from the same provider, mainly as mounted specimens, for a Portuguese private collection of Neotropical fauna. In the early 20th Century, it was donated to the Museum that is now the MHNC-UP. NEW INFORMATION: The information about the majority of these specimens is now available for consultation on the GBIF platform after curation of all specimens and digital cleaning of the associated metadata. In the process, hundreds of non-catalogued specimens were found and taxonomic and spatial information was updated for many of the specimens.

Fundamental privacy rights in a pandemic state.

Faced with the emergence of the Covid-19 pandemic, and to better understand and contain the disease's spread, health organisations increased the collaboration with other organisations sharing health data with data scientists and researchers. Data analysis assists such organisations in providing information that could help in decision-making processes. For this purpose, both national and regional health authorities provided health data for further processing and analysis. Shared data must comply with existing data protection and privacy regulations. Therefore, a robust de-identification procedure must be used, and a re-identification risk analysis should also be performed. De-identified data embodies state-of-the-art approaches in Data Protection by Design and Default because it requires the protection of direct and indirect identifiers (not just direct). This article highlights the importance of assessing re-identification risk before data disclosure by analysing a data set of individuals infected by Covid-19 that was made available for research purposes. We stress that it is highly important to make this data available for research purposes and that this process should be based on the state of the art methods in Data Protection by Design and by Default. Our main goal is to consider different re-identification risk analysis scenarios since the information on the intruder side is unknown. Our conclusions show that there is a risk of identity disclosure for all of the studied scenarios. For one, in particular, we proceed to an example of a re-identification attack. The outcome of such an attack reveals that it is possible to identify individuals with no much effort.

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD – Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 – 4 μg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 μg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 μg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 μg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 μg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 μg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 μg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 μg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 μg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 μg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 μg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 μg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD ­ Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 ­ 4 µg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 µg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 µg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 µg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 µg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 µg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 µg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 µg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 µg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 µg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 µg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 µg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

MYOC Gene Sequencing Analysis in Primary Open-Angle Glaucoma Patients from the Centre Region of Portugal.

INTRODUCTION: Primary open-angle glaucoma is the most frequent subtype of glaucoma. Relatives of primary open-angle glaucoma patients have an increased risk of developing the disease, suggesting a genetic predisposition to the disease. MYOC was the first primary open-angle glaucoma-causing gene identified. This study aimed to identify sequence variations in the MYOC gene that may be responsible for the phenotype in a group of primary open-angle glaucoma patients from the Centre Region of Portugal. MATERIAL AND METHODS: The three coding exons and the proximal splicing junctions of the MYOC gene were studied using a PCR sequencing approach in a group of 99 primary open-angle glaucoma patients. RESULTS: The sequencing analysis enabled the identification of 20 variants, including four in the promoter region, seven in the introns and nine in exons one and three, of which four were missense variants. DISCUSSION: Initially, all four missense sequence variations identified were considered candidates to glaucoma causing disease mutations. However, after literature review, only variant c.1334C>T (Ala445Val) remained as likely responsible for mild late-onset normal tension glaucoma. CONCLUSION: This is the first study performed in a group of primary open-angle glaucoma patients from the Centre Region of Portugal, contributing to the identification of one genetic variant in the MYOC gene and reinforcing the hypothesis that normal tension glaucoma could be also due to MYOC gene mutations.

Introdução: O glaucoma primário de ângulo-aberto é o subtipo mais frequente de glaucoma. Os familiares de doentes com glaucoma primário de ângulo-aberto têm um risco maior de desenvolverem a doença, o que sugere uma predisposição genética para a doença. MYOC foi o primeiro gene causador de glaucoma primário de ângulo-aberto a ser identificado. Este estudo pretendeu identificar variações de sequência no gene MYOC que possam ser responsáveis pelo fenótipo num grupo de doentes com glaucoma primário de ângulo-aberto da Região Centro de Portugal. Material e Métodos: Os três exões codificantes e as regiões adjacentes do gene MYOC foram estudados utilizando o método de PCR-sequenciação num grupo de 99 doentes com glaucoma primário de ângulo aberto. Resultados: A análise de sequenciação permitiu identificar 20 variantes, incluindo quatro na região promotora, sete nos intrões e nove nos exões um e três, das quais quatro eram variantes missense. Discussão: Inicialmente, todas as quatro variações de sequência missense identificadas foram consideradas candidatas a mutações causadoras de glaucoma. No entanto, após análise da literatura, somente a variante c.1334C>T (Ala445Val) permaneceu como provável responsável pelo glaucoma de pressão normal de início tardio. Conclusão: Este é o primeiro estudo realizado num grupo de doentes com glaucoma primário de ângulo aberto da Região Centro de Portugal, contribuindo para a identificação de uma variante genética no gene MYOC e reforçando a hipótese de que o glaucoma de pressão normal também poderá ser causado por mutações no gene MYOC.

Use of Sensors and Analyzers Data for Load Forecasting: A Two Stage Approach.

The increase in sensors in buildings and home automation bring potential information to improve buildings' energy management. One promissory field is load forecasting, where the inclusion of other sensors' data in addition to load consumption may improve the forecasting results. However, an adequate selection of sensor parameters to use as input to the load forecasting should be done. In this paper, a methodology is proposed that includes a two-stage approach to improve the use of sensor data for a specific building. As an innovation, in the first stage, the relevant sensor data is selected for each specific building, while in the second stage, the load forecast is updated according to the actual forecast error. When a certain error is reached, the forecasting algorithm (Artificial Neural Network or K-Nearest Neighbors) is trained with the most recent data instead of training the algorithm every time. Data collection is provided by a prototype of agent-based sensors developed by the authors in order to support the proposed methodology. In this case study, data over a period of six months with five-minute time intervals regarding eight types of sensors are used. These data have been adapted from an office building to illustrate the advantages of the proposed methodology.