Staghorn Calculi: an Unusual and Serious Clinical Case

Introdução: Este artigo tem como objectivo apresentar um caso clínico de litíase coraliforme que exemplifica a gravidade resultante desta patologia. Caso Clínico: Caso clínico de uma doente do sexo feminino, 43 anos, sem antecedentes pessoais de relevo, que recorreu ao Serviço de Urgência por prostração, astenia e anorexia. Foi-lhe diagnosticada insuficiência renal grave, litíase coraliforme bilateral e hidronefrose com conteúdo não puro no excretor. A doente foi submetida a colocação bilateral de nefrostomias e uma semana depois, num contexto de pionefrose à esquerda e sépsis, foi submetida a nefrectomia total à esquerda. Ficou a realizar hemodiálise em ambulatório. Posteriormente concluiu-se perda irreversível da função renal, com consequente nefrectomia direita. Discussão: Este caso constitui um exemplo da gravidade resultante da litíase coraliforme. Mesmo sem manifestação clínica prévia, pode causar insuficiência renal avançada, com infecção urinária grave e sépsis que colocam a vida em risco

REALMS Study: Real-World Effectiveness and Safety of Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis in Portugal

Background: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). Objectives: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. Methods: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. Results: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. Conclusions: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.info:eu-repo/semantics/publishedVersio

Ground-motion networks in the Groningen field: usability and consistency of surface recordings

Several strong-motion networks have been installed in the Groningen gas field in the Netherlands to record ground motions associated with induced earthquakes. There are now more than 450 permanent surface accelerographs plus a mobile array of 450 instruments, which, in addition to many instrumented boreholes, yield a wealth of data. The database of recordings has been of fundamental importance to the development of ground-motion models that form a key element of the seismic hazard and risk estimations for the field. In order to maximise the benefit that can be derived from these recordings, this study evaluates the usability of the recordings from the different networks, in general terms and specifically with regards to the frequency ranges with acceptable signal-to-noise ratios. The study also explores the consistency among the recordings from the different networks, highlighting in particular how a configuration error was identified and resolved. The largest accelerograph network consists of instruments housed in buildings around the field, frequently installed on the lower parts of walls rather than on the floor. A series of experiments were conducted, using additional instruments installed adjacent to these buildings and replicating the installation configuration in full-scale shake table tests, to identify the degree to which structural response contaminated the recordings. The general finding of these efforts was that for PGV and oscillator periods above 0.1 s, the response spectral ordinates from these recordings can be used with confidence

Consenso Português para a Identificação Precoce de Esclerose Múltipla Secundária Progressiva: Painel Delphi

Introduction: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. Material and methods: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. Results: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. Conclusion: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.Introdução: A esclerose múltipla é uma doença de evolução heterogénea. A identificação precoce da forma secundária progressiva é um desafio clínico, carecendo da definição de biomarcadores e ferramentas de diagnóstico aplicáveis na fase de transição da forma surto-remissão para a forma secundária progressiva. Este trabalho teve como objetivo estabelecer um consenso nacional português sobre a monitorização dos doentes e das variáveis clínicas mais relevantes para a identificação precoce da progressão da esclerose múltipla. Material e Métodos: Um painel Delphi constituído por 11 neurologistas portugueses respondeu a duas rondas de perguntas entre julho e agosto de 2021. Na primeira ronda foram incluídas 39 questões relacionadas com a avaliação funcional, cognitiva, imagiológica, de biomarcadores e outras, e na segunda, as questões para as quais não foi atingido consenso (menos de 80% de concordância) na primeira ronda voltaram a ser submetidas a avaliação pelo painel. Resultados: A taxa de resposta foi de 100% em ambas as rondas e 33 das 39 questões (84,6%) atingiram concordância. Foi atingido consenso relativamente ao tempo de monitorização dos doentes, às escalas de avaliação a empregar e a variáveis clínicas tais como o grau de atrofia cerebral ou redução da mobilidade, cuja alteração é sugestiva de esclerose múltipla secundária progressiva. Adicionalmente, os dispositivos digitais foram considerados ferramentas com potencial para identificar a progressão da doença. A maioria das questões para as quais não foi obtido consenso dizem respeito à avaliação cognitiva, estando as restantes inseridas nos domínios funcional e imagiológico. Conclusão: Foi obtido consenso para a determinação do intervalo de monitorização e para a maioria das variáveis clínicas. A maioria das questões sem consenso estavam relacionadas com a confirmação do diagnóstico de progressão tendo em conta apenas um teste/domínio, realçando a natureza multifatorial da esclerose múltipla.info:eu-repo/semantics/publishedVersio

Free daily newspapers : too strong incentives to print?

A free daily newspaper distributes news to readers and sells ad-space to advertisers, having private information about its audience. For a given number of distributed copies, depending on the type of audience (favorable or unfavorable), the newspaper may either have a large readership or a small readership. A large readership provides a greater return to advertisers, because ads are visualized by more people. A favorable audience has also the advantage of requiring a lower distribution cost (for a given number of distributed copies), because readers are willing to exert more effort to obtain a copy of the free newspaper and are less likely to reject a copy that is handed to them. We find that when the audience is unfavorable, the number of distributed copies and the price of ad-space coincide with those of the perfect information scenario. In contrast, if the audience is favorable, the newspaper prints extra copies to send a credible signal to the advertisers that the audience is favorable. Overprinting is not necessarily welfare-detrimental since readers benefit from the existence of additional copies.info:eu-repo/semantics/publishedVersio

A pre-Caloris synchronous rotation for Mercury

The planet Mercury is locked in a spin-orbit resonance where it rotates three times about its spin axis for every two orbits about the Sun. The current explanation for this unique state assumes that the initial rotation of this planet was prograde and rapid, and that tidal torques decelerated the planetary spin to this resonance. When core-mantle boundary friction is accounted for, capture into the 3/2 resonance occurs with a 26% probability, but the most probable outcome is capture into one of the higher-order resonances. Here we show that if the initial rotation of Mercury were retrograde, this planet would be captured into synchronous rotation with a 68% probability. Strong spatial variations of the impact cratering rate would have existed at this time, and these are shown to be consistent with the distribution of pre-Calorian impact basins observed by Mariner 10 and MESSENGER. Escape from this highly stable resonance is made possible by the momentum imparted by large basin-forming impact events, and capture into the 3/2 resonance occurs subsequently under favourable conditions.Comment: Nature Geosci., 201

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

A Randomized Double-Blind Study Comparing the Efficacy and Safety of Orlistat Versus Placebo in Obese Patients with Mild to Moderate Hypercholesterolemia

INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters

EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization for photothermal therapy

The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer -coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100-200 nm) showed a plasmon absorption band located within the near infrared range (650-900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0-25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.Support was provided by: Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012 [https://www.fct.pt/apoios/projectos)]. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) [https://www.fct.pt/apoios/projectos]; European Commission through the project H2020-644242-SAPHELY (https://saphely.eu/project.php) and the project H2020-634013-2-PHOCNOSIS [http://cordis.europa.eu/project/rcn/193268_en.html].The authors would like to thank Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI). The authors acknowledge the funding from the European Commission through the project H2020-644242-SAPHELY and the project H2020-634013-2-PHOCNOSIS. Finally, the authors would also like to thank the master student Joao Lopes from Universidade Lusofona (Portugal) for the help with in vitro cytotoxic assays. Isabel Correia acknowledges FCT for Investigator FCT contract.info:eu-repo/semantics/publishedVersio

Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript