Robotic implantation of intracerebral electrodes for deep brain stimulation

This dissertation objective is to contribute for the development of a robotic system towards neurosurgery assistance in Deep Brain Stimulation (DBS) stereotactic procedures. Being DBS neurosurgery typically a long, physically and cognitively demanding procedure; the introduction of a robotic assistant to hold, manipulate and position instrumentation would improve the medical team working conditions and lead to better surgery outcomes. Upon understanding how could the robot be used and what robotic systems were adequate to the task, we implemented a simulation environment to emulate several industrial robot manipulators and the operating room. It was also developed each robot geometric and differential kinematic equations, and control algorithms specifically oriented for DBS neurosurgery assistance. Taking into account the operating room arrangement, the robot characteristics and task requirements, we selected the most apt industrial robotic manipulator and further elaborated on its placement and orientation to achieve utmost performance.This work has been partially financed by projects FP7 Marie Curie ITN - NETT (project no289146), FCT FCOMP-01-0124-FEDER-022674, Pest-C/MAT-UI0013/2011 (FCT grant ref. UMINHO/BIC/8/2012) and FCT PhD grant (ref. SFRH/BD/86499/2012)

Recurrent hypercortisolism after removal of an ACTH secretor pituitary adenoma associated with an adrenal macronodule

A 29 years old patient was sent to our Outpatient Clinic of Endocrinology presenting clinic of hypercortisolism. Laboratorial study: High urinary free cortisol (UFC); serum cortisol - 25 microg/dl (8 am) (5-25) and 20 microg/dL (11pm); ACTH - 20 pg/mL (9-52) (8 am) and 14 pg/mL (11 pm); serum cortisol after dexamethasone suppression test: 14,9 mg/dL; CRH test: elevation of ACTH; Pituitary MRI: microadenoma; abdominal CT: nodule on the left adrenal. During inferior petrosal sinus sampling with CRH stimulation, ACTH reached 368 pg/mL on the right and 136 pg/mL on the left side. The patient was submitted to transsphenoidal surgery. After surgery, hypertension and physical stigmata improved. In 2006, a relapse of Cushing syndrome was suspected due to worsening of hypertension and increase of weight. A slight increase of UFC, undetectable ACTH and serum cortisol after dexamethasone suppression test equal to 16 microg/dL were found. On abdominal CT, the adrenal nodule kept the same characteristics. In December 2006, the patient was submitted to left adrenalectomy. After surgery, blood pressure normalized, UFC and serum cortisol were reduced, needing substitutive therapy. Progressive tapering of hydrocortisone doses lead to discontinuation in March 2007. He is clinically well, without any treatment. This is an unusual case, in which after surgical cure of Cushing disease, secretory autonomy of a coexisting adrenal nodule occurred. This clinical case is relevant, pointing out the complexity of hypercortisolism cases and the need of long follow-up

Economics of Chronic Diseases Protocol: Cost-effectiveness modelling and the future burden of non-communicable disease in Europe

Background: The majority of chronic disease is caused by risk factors which are mostly preventable. Effective interventions to reduce these risks are known and proven to be applicable to a variety of settings. Chronic disease is generally developed long before the fatal outcome, meaning that a lot of people spend a number of years in poor health. Effective prevention measures can prolong lives of individuals and significantly improve their quality of life. However, the methods to measure cost-effectiveness are a subject to much debate. The Economics of Chronic Diseases project aims to establish the best possible methods of measuring cost-effectiveness as well as develop micro-simulation models apt at projecting future burden of chronic diseases, their costs and potential savings after implementation of cost-effective interventions. Method: This research project will involve eight European countries: Bulgaria, Finland, Greece, Lithuania, The Netherlands, Poland, Portugal and the United Kingdom (UK). A literature review will be conducted to identify scientific articles which critically review the methods of cost-effectiveness. Contact will be made health economists to inform and enrich this review. This evidence will be used as a springboard for discussion at a meeting with key European stakeholders and experts with the aim of reaching a consensus on recommendations for cost-effectiveness methodology. Epidemiological data for coronary heart disease, chronic kidney disease, type 2 diabetes and chronic obstructive pulmonary disease will be collected along with data on time trends in three major risk factors related to these diseases, specifically tobacco consumption, blood pressure and body mass index. Economic and epidemiological micro-simulation models will be developed to asses the future distributions of risks, disease outcomes, healthcare costs and the cost-effectiveness of interventions to reduce the burden of chronic diseases in Europe. Discussion: This work will help to establish the best methods of measuring cost-effectiveness of health interventions as well as test a variety of scenarios to reduce the risk factors associated with selected chronic diseases. The modelling projections could be used to inform decisions and policies that will implement the best course of action to curb the rising incidence of chronic diseases.The EConDA project is supported by the European Commission Health Programme and the Executive Agency for Health and Consumers, grant agreement n0 20121213.www.econdaproject.e

ACTH-dependent Cushing's syndrome: a revision of 43 cases

AIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients

Design, Metallurgical Features, and Mechanical Behaviour of NiTi Endodontic Instruments from Five Different Heat-Treated Rotary Systems

UIDB/50025/2020-2023The current study aimed to compare the F1 endodontic instruments from five different heat-treated rotary systems regarding their design, metallurgical properties, and mechanical performance. Five F1 root canal shaping instruments (ProTaper Gold [PTG], Premium Taper Gold, Go-Taper Flex, EdgeTaper Platinum, and Super Files Blue)—plus, a conventional ProTaper Universal (PTU)—which were evaluated regarding their design, nickel/titanium ratio, phase transformation temperatures, microhardness, cyclic fatigue, and torsional and bending strengths. Mood's median test was used for the statistical comparison with a significance set at 5%. The instruments were similar regarding the nickel/titanium ratio and overall design. Go-Taper Flex had the closest transformation temperatures to PTG. PTU and Go-Taper Flex had the highest microhardness (408.3 and 410.5 HVN). The time to fracture of Super Files Blue was three and seven times higher than PTG and PTU, respectively. No difference was observed in the maximum torque to fracture among PTG (1.30 N·cm) and the other systems, except for the Premium Taper Gold (1.05 N·cm) and Go-Taper Flex (1.10 N·cm). Significantly lower bending loads than PTG (269.2 gf) were observed for the EdgeTaper Platinum (158.3 gf) and Premium Taper Gold (103.5 gf) instruments. Super Files Blue outperformed PTG in the cyclic fatigue test, while EdgeTaper Platinum and Premium Taper Gold were more flexible. Premium Taper Gold and Go-Taper Flex showed lower torsional strength.publishersversionpublishe

Functional and sequence-based metagenomics to uncover carbohydrate-degrading enzymes from composting samples

The online version contains supplementary material available at: https://doi.org/10.1007/s00253-023-12627-9.The renewable, abundant, and low-cost nature of lignocellulosic biomass can play an important role in the sustainable production of bioenergy and several added-value bioproducts, thus providing alternative solutions to counteract the global energetic and industrial demands. The efficient conversion of lignocellulosic biomass greatly relies on the catalytic activity of carbohydrate-active enzymes (CAZymes). Finding novel and robust biocatalysts, capable of being active under harsh industrial conditions, is thus imperative to achieve an economically feasible process. In this study, thermophilic compost samples from three Portuguese companies were collected, and their metagenomic DNA was extracted and sequenced through shotgun sequencing. A novel multi-step bioinformatic pipeline was developed to find CAZymes and characterize the taxonomic and functional profiles of the microbial communities, using both reads and metagenome-assembled genomes (MAGs) as input. The samples' microbiome was dominated by bacteria, where the classes Gammaproteobacteria, Alphaproteobacteria, and Balneolia stood out for their higher abundance, indicating that the degradation of compost biomass is mainly driven by bacterial enzymatic activity. Furthermore, the functional studies revealed that our samples are a rich reservoir of glycoside hydrolases (GH), particularly of GH5 and GH9 cellulases, and GH3 oligosaccharide-degrading enzymes. We further constructed metagenomic fosmid libraries with the compost DNA and demonstrated that a great number of clones exhibited $\beta$-glucosidase activity. The comparison of our samples with others from the literature showed that, independently of the composition and process conditions, composting is an excellent source of lignocellulose-degrading enzymes. To the best of our knowledge, this is the first comparative study on the CAZyme abundance and taxonomic/functional profiles of Portuguese compost samples.Open access funding provided by FCT|FCCN (b-on). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, the projects LIGNOZYMES—Metagenomics approach to unravel the potential of lignocellulosic residues towards the discovery of novel enzymes (POCI-01–0145-FEDER-029773), and B3iS—Biodiversity and Bioprospecting of Biosurfactants in Saline Environments (PTDC/BII-BIO/5554/2020); and by RNCA Advanced Computing Project MetaLignoZymes, metagenomic analysis of lignocellulosic residues towards the discovery of novel enzymes (CPCA/A0/408464/2021).info:eu-repo/semantics/publishedVersio

Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential

Mitochondrial proteins are coded by nuclear (nDNA) and mitochondrial (mtDNA) genes, implying a complex cross-talk between the two genomes. Here we investigated the diversity displayed in 104 nuclear-coded mitochondrial proteins from 1,092 individuals from the 1000 Genomes dataset, in order to evaluate if these genes are under the effects of purifying selection and how that selection compares with their mitochondrial encoded counterparts. Only the very rare variants (frequency < 0.1%) in these nDNA genes are indistinguishable from a random set from all possible variants in terms of predicted pathogenicity score, but more frequent variants display distinct signs of purifying selection. Comparisons of selection strength indicate stronger selection in the mtDNA genes compared to this set of nDNA genes, accounted for by the high hydrophobicity of the proteins coded by the mtDNA. Most of the predicted pathogenic variants in the nDNA genes were restricted to a single continental population. The proportion of individuals having at least one potential pathogenic mutation in this gene set was significantly lower in Europeans than in Africans and Asians. This difference may reflect demographic asymmetries, since African and Asian populations experienced main expansions in middle Holocene, while in Europeans the main expansions occurred earlier in the post-glacial period

Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays

In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent, and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings

Resolving the ancestry of Austronesian-speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The “out-of-Taiwan” model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion

Genomic Diversity and Antimicrobial Susceptibility of Invasive Neisseria meningitidis in South Africa, 2016–2021

Background: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W, and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016–2021. Methods: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. Results: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%), and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9, or penA14. Conclusions: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008; however, peni was higher than previously reported, and occurred in a variety of lineages