Síndrome do osso trígono

A causa mais frequente da síndrome de conflito posterior do tornozelo envolve o osso trígono e o processo talar, chamando-se síndrome do osso trígono à compressão sintomática de tecidos moles e osso a nível do intervalo calcâneo-tibial. Trata-se de uma entidade controversa, atualmente ainda com evidência limitada na literatura. A presença do osso trígono é na maior parte dos casos apenas um achado imagiológico sem tradução clínica, no entanto o seu traumatismo, agudo ou crónico, em movimentos de flexão plantar forçada pode ser responsável pela sua lesão e conversão sintomática. O diagnóstico é feito pela clínica e pela evidência imagiológica e é frequentemente subdiagnosticado ou tem diagnóstico tardio. É necessário um nível elevado de suspeição para diagnóstico precoce, que é fundamental não só para iniciar rapidamente o tratamento adequado para alívio sintomático, como também em termos de prognóstico. O tratamento pode ser conservador ou cirúrgico, envolvendo a ressecção deste ossículo acessório, por técnicas de cirurgia aberta ou minimamente invasivas de artroscopia ou endoscopia. O presente trabalho faz uma revisão da literatura científica existente sobre este tema. Introduzimos com a definição da síndrome, noções anatómicas e fisiopatológicas, seguindo-se a apresentação dos sinais e sintomas clínicos e dos meios complementares de diagnóstico e finalizando com as várias abordagens terapêuticas, tanto conservadora como cirúrgica. São descritas e comparadas entre si as três técnicas cirúrgicas mais praticadas atualmente, a cirurgia aberta, a artroscópica subtalar e a endoscópica

Pé de Charcot – Um caso clínico

A artropatia neuropática de Charcot é uma doença osteoarticular primária progressiva que atinge mais frequentemente o pé e tornozelo. Trata-se de uma patologia característica de doentes diabéticos de longa evolução e com mau controlo glicémico. Aceita-se hoje em dia que esta condição tem origem numa combinação de hiperémia/inflamação óssea, osteopénia e défices sensitivo-motores, ou seja, uma combinação das clássicas teorias neuro-traumática e neuro-vascular, com a nova teoria inflamatória. A doença pode estar na fase aguda, activa ou inflamatória, verificando-se um pé edemaciado, com calor e eritema, ou na fase crónica ou inactiva, onde são características deformidades acentuadas devido a luxações e fracturas. O diagnóstico faz-se sobretudo pela clínica, podendo a radiografia, a ressonância magnética e a cintigrafia óssea serem úteis, nomeadamente em termos de diagnóstico diferencial. Os objectivos do tratamento são analgesia, estabilidade articular, pé plantígrado, marcha e prevenção de úlceras, deformidades e amputação. A opção de tratamento depende da fase de doença, local, gravidade e grau de ulceração. Para a fase aguda reserva-se imobilização com bota gessada por 2-4 meses e descarga, enquanto na fase crónica está indicada imobilização com ortóteses tornozelo-pé ou calçado especializado ou correcção cirúrgica das deformidades em casos específicos. Casos de dor incapacitante, exostose, úlcera recorrente, deformidades acentuadas e luxações ou fracturas, têm indicação de correcção cirúrgica, que pode ir desde exostosectomia, a artrodese ou mesmo amputação. Apresenta-se um caso clínico de um caso de pé de Charcot com evolução rápida de destruição osteo-articular em 6meses. Quanto a classificações trata-se de Sanders-Frykberg grau III-IV (sub-talar, médiotársica),Brodsky grau II (sub-talar, talo-navicular, calcâneo-cuboideia) e Eichenholtz grau III (estadio crónico/consolidação - Deformidade). Face a deformidade acentuada instável e dor incapacitante, opta-se por tratamento cirúrgico com artrodese tripla do tornozelo com encavilhamento calcâneo-tibial retrógrado. Intraoperatoriamente verifica-se destruição osteo-articular necrótica acentuada do astrágalo e parcial do calcâneo, é então feita astragalectomia, encavilhamento calcâneo-tibial retrógrado e artrodese com 2 parafusos canulados: calcâneo-tibial e fíbulo-tíbio-navicular, bem como aplicação de aloenxerto. É feita imobilização com bota gessada, que é renovada em consulta a cada 2 semanas sob vigilância. A imobilização e descarga são mantidas até sinais deconsolidação. Quanto a prognóstico é conhecida a taxa elevada de complicações deste tipo de procedimento no pé de Charcot, estando relatadas percentagens superiores a 70%, nomeadamente de infecção, mau posicionamento de material cirúrgico, úlcera recorrente e fractura. São fundamentais para boa evolução manter a descarga e imobilização prolongada, a renovação de imobilização e inspecção frequente do pé e um bom controlo da glicémia. Face à localização e presença de deformidade acentuada e lesão cutânea, este caso clínico apresenta um prognóstico reservado, podendo eventualmente por complicações progredir para amputação

A relocatable ocean model in support of environmental emergencies

During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio

Emulation of a Target Trial From Observational Data to Compare Effectiveness of Casirivimab/Imdevimab and Bamlanivimab/Etesevimab for Early Treatment of Non-Hospitalized Patients With COVID-19

OBJECTIVES: Comparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta. METHODS: Allocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7. Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period. RESULTS: COVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p<0.001) on D7. CONCLUSIONS: In a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response

Deducing the source and composition of rare earth mineralising fluids in carbonatites: insights from isotopic (C, O, 87Sr/86Sr) data from Kangankunde, Malawi

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Carbonatites host some of the largest and highest grade rare earth element (REE) deposits but the composition and source of their REE-mineralising fluids remains enigmatic. Using C, O and 87Sr/86Sr isotope data together with major and trace element compositions for the REE-rich Kangankunde carbonatite (Malawi), we show that the commonly observed, dark brown, Fe-rich carbonatite that hosts REE minerals in many carbonatites is decoupled from the REE mineral assemblage. REE-rich ferroan dolomite carbonatites, containing 8–15 wt% REE2O3, comprise assemblages of monazite-(Ce), strontianite and baryte forming hexagonal pseudomorphs after probable burbankite. The 87Sr/86Sr values (0.70302–0.70307) affirm a carbonatitic origin for these pseudomorph-forming fluids. Carbon and oxygen isotope ratios of strontianite, representing the REE mineral assemblage, indicate equilibrium between these assemblages and a carbonatite-derived, deuteric fluid between 250 and 400 °C (δ18O + 3 to + 5‰VSMOW and δ13C − 3.5 to − 3.2‰VPDB). In contrast, dolomite in the same samples has similar δ13C values but much higher δ18O, corresponding to increasing degrees of exchange with low-temperature fluids (< 125 °C), causing exsolution of Fe oxides resulting in the dark colour of these rocks. REE-rich quartz rocks, which occur outside of the intrusion, have similar δ18O and 87Sr/86Sr to those of the main complex, indicating both are carbonatite-derived and, locally, REE mineralisation can extend up to 1.5 km away from the intrusion. Early, REE-poor apatite-bearing dolomite carbonatite (beforsite: δ18O + 7.7 to + 10.3‰ and δ13C −5.2 to −6.0‰; 87Sr/86Sr 0.70296–0.70298) is not directly linked with the REE mineralisation.This project was funded by the UK Natural Environment Research Council (NERC) SoS RARE project (NE/M011429/1) and by NIGL (NERC Isotope Geoscience Laboratory) Project number 20135

New Insight into the Transcarbamylase Family: The Structure of Putrescine Transcarbamylase, a Key Catalyst for Fermentative Utilization of Agmatine

Transcarbamylases reversibly transfer a carbamyl group from carbamylphosphate (CP) to an amine. Although aspartate transcarbamylase and ornithine transcarbamylase (OTC) are well characterized, little was known about putrescine transcarbamylase (PTC), the enzyme that generates CP for ATP production in the fermentative catabolism of agmatine. We demonstrate that PTC (from Enterococcus faecalis), in addition to using putrescine, can utilize L-ornithine as a poor substrate. Crystal structures at 2.5 Å and 2.0 Å resolutions of PTC bound to its respective bisubstrate analog inhibitors for putrescine and ornithine use, N-(phosphonoacetyl)-putrescine and δ-N-(phosphonoacetyl)-L-ornithine, shed light on PTC preference for putrescine. Except for a highly prominent C-terminal helix that projects away and embraces an adjacent subunit, PTC closely resembles OTCs, suggesting recent divergence of the two enzymes. Since differences between the respective 230 and SMG loops of PTC and OTC appeared to account for the differential preference of these enzymes for putrescine and ornithine, we engineered the 230-loop of PTC to make it to resemble the SMG loop of OTCs, increasing the activity with ornithine and greatly decreasing the activity with putrescine. We also examined the role of the C-terminal helix that appears a constant and exclusive PTC trait. The enzyme lacking this helix remained active but the PTC trimer stability appeared decreased, since some of the enzyme eluted as monomers from a gel filtration column. In addition, truncated PTC tended to aggregate to hexamers, as shown both chromatographically and by X-ray crystallography. Therefore, the extra C-terminal helix plays a dual role: it stabilizes the PTC trimer and, by shielding helix 1 of an adjacent subunit, it prevents the supratrimeric oligomerizations of obscure significance observed with some OTCs. Guided by the structural data we identify signature traits that permit easy and unambiguous annotation of PTC sequences

Altered Intracellular Localization and Mobility of SBDS Protein upon Mutation in Shwachman-Diamond Syndrome

Shwachman-Diamond Syndrome (SDS) is a rare inherited disease caused by mutations in the SBDS gene. Hematopoietic defects, exocrine pancreas dysfunction and short stature are the most prominent clinical features. To gain understanding of the molecular properties of the ubiquitously expressed SBDS protein, we examined its intracellular localization and mobility by live cell imaging techniques. We observed that SBDS full-length protein was localized in both the nucleus and cytoplasm, whereas patient-related truncated SBDS protein isoforms localize predominantly to the nucleus. Also the nucleo-cytoplasmic trafficking of these patient-related SBDS proteins was disturbed. Further studies with a series of SBDS mutant proteins revealed that three distinct motifs determine the intracellular mobility of SBDS protein. A sumoylation motif in the C-terminal domain, that is lacking in patient SBDS proteins, was found to play a pivotal role in intracellular motility. Our structure-function analyses provide new insight into localization and motility of the SBDS protein, and show that patient-related mutant proteins are altered in their molecular properties, which may contribute to the clinical features observed in SDS patients