Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Bacterial Production of a Pederin Analogue by a Free-Living Marine Alphaproteobacterium.

The polyketide pederin family are cytotoxic compounds isolated from insects, lichen, and marine sponges. During the past decade, different uncultivable bacteria symbionts have been proposed as the real producers of these compounds, such as those found in insects, lichen, and marine sponges, and their trans-AT polyketide synthase gene clusters have been identified. Herein we report the isolation and biological activities of a new analogue of the pederin family, compound 1, from the culture of a marine heterotrophic alphaproteobacterium, Labrenzia sp. PHM005. This is the first report of the production of a pederin-type compound by a free-living marine bacteria that could be cultured in the laboratory.

Newborn screening for Fabry disease in the north-west of Spain.

Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy is available to treat patients, who often experience delayed diagnosis. A newborn screening for Fabry disease was performed to study the prevalence of the pathology and to evaluate the possibility to implement the test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males and 7025 females) and carried out a diagnostic study by fluorometric measurement of α-galactosidase A enzymatic activity and GLA gene sequencing. We detected one patient with a mutation in GLA associated with classical Fabry Disease (M290I), ten subjects carrying genetic variants of uncertain diagnosis (S126G, R118C, A143T), and a girl with the non-characterized variant F18Y, which was not previously described. Additional 25 samples presented nucleotide substitutions described as polymorphisms (D313Y, rs2071225, and rs2071397). The estimated prevalence for Fabry disease in north-western Spanish males is of 0.013%. CONCLUSION: These results confirm that the prevalence of Fabry disease is underestimated and systematic screening is feasible; however, further characterization of variants of uncertain clinical significance is necessary to establish protocols of patients' management. What is Known: • Fabry disease is a rare disease of delayed diagnosis, whose prevalence is underestimated. However, early diagnosis is important for better efficiency of the current available treatment. What is New: • This newborn screening for Fabry disease performed on Spanish population reveals a prevalence of genetic alterations in GLA of 0.1% in males (0.013% with classic Fabry disease) and also characterizes these modifications in order to discriminate between pathogenic mutations and genetic variants of unknown significance.

Beyond the 510(k): The regulation of novel moderate-risk medical devices, intellectual property considerations, and innovation incentives in the FDA's De Novo pathway.

Moderate-risk medical devices constitute 99% of those that have been regulated by the U.S. Food and Drug Administration (FDA) since it gained authority to regulate medical technology nearly five decades ago. This article presents an analysis of the interaction between the 510(k) process -the historically dominant path to market for most medical devices- and the De Novo pathway, a more recent alternative that targets more novel devices, including those involving new technologies, diagnostics, hardware, and software. The De Novo pathway holds significant potential for innovators seeking to define new categories of medical devices, as it represents a less burdensome approach than would have otherwise been needed historically. Moreover, it supports the FDA in its effort to modernize the long-established 510(k) pathway by promoting the availability of up-to-date device "predicates" upon which subsequent device applications can be based, reflecting positive spillovers that are likely to encourage manufacturers to adopt current state-of-the-art technologies and modern standards of safety and effectiveness. We analyze the of characteristics all the De Novo classification requests to date, including the submission type, trends, FDA review times, and device types. After characterizing how the De Novo process has been used over time, we discuss its unique challenges and opportunities with respect to medical device software and AI-enabled devices, including considerations for intellectual property, innovation, and competition economics.

New Plastic Crack-Tip Opening Displacement Tool Based on Digital Image Correlation for Estimating the Fatigue-Crack-Growth Law on 316L Stainless Steel.

This work presents a new approach for studying crack growth resulting from fatigue, which utilizes the plastic contribution of crack-tip opening displacement (CTODp). CTODp is used to predict austenitic stainless-steel crack propagation. Unlike linear elastic fracture mechanics analysis, the method presented here is also helpful for tasks other than small-scale yielding. The approach was based on correlating full-field displacement information with post-processing digital images. This work describes a detailed post-processing protocol that can be used to calculate CTODp. The results for steel compact-tension specimens were especially promising. Of note, there was a linear relationship between the propagation rate of fatigue cracks and the CTODp range.

Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment.

Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and PM060431 (4), were isolated from the cell extract of the marine-derived Streptomyces albus POR-04-15-053. Their structures were elucidated by a combination of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS. They consist of an α-methoxy-γ-pyrone ring containing a highly substituted tetraene side chain glycosylated at C-10 in the case of 1 and 4. Compounds 1 and 4 displayed strong cytotoxicity against three human tumor cell lines with GI50 values in the submicromolar range, whereas 2 showed subnanomolar activity as an inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of EGF-mediated AP1 trans-activation and EGF-mediated ERK activation and slight inhibition of EGF-mediated JNK activation. Taken together, these results suggest that members of the pyranone family of compounds could be developed as potential antitumor agents.

Study of Recycling Potential of FFP2 Face Masks and Characterization of the Plastic Mix-Material Obtained. A Way of Reducing Waste in Times of Covid-19.

The purpose of this study is to investigate how to recycle FFP2 face masks used during Covid-19 pandemic without using previous sorting process and to characterize the properties of the material obtained. The way of splitting and processing the mixture of materials was studied as well as the final properties such as chemical, thermal and mechanical characteristics. The resulting recycled material is a blend of polymers with such mechanical and thermal properties that could be used as an alternative to recycled PP (polypropylene). Avoidance of previous sorting process gives the face mask recycling a new and simplified way of preventing this material to be disposed in environment and an opportunity of second life for the polymers they are made of. With this work we lay the basis to reduce the plastic pollution related with the recommended use of face masks during Covid-19 pandemic.

Vertical Dimension of Occlusion: A comparative study between Anthropometric and Knebelman's craniometric methods.

The masticatory system changes as time passes. The vertical dimension of occlusion (VDO) undergoes alterations due to temporomandibular joint disorders which in turn may be caused by related muscle modifications or pathological tooth wear. There are many methods to measure VDO. Among these, the anthropometric method and Knebelman's craniometric method have been shown to be the most closely related to facial biotype. The aim of this study was to compare data recorded with those two methods. A descriptive cross-sectional study was performed with a total 200 patients. A vernier caliper was used to measure facial landmarks. Results were analyzed using paired t-test, setting the level of significance at p<0.05. There was no significant difference between the two methods but Knebelman's method had less variability. Results suggest that Knebelman's method should provide more reliability for determining VDO in all the facial biotypes studied.

El sistema masticatorio cambia con el paso del tiempo. La dimensión vertical oclusal sufre alteraciones que se atribuyen a trastornos temporomandibulares a su vez causados por modificaciones en la musculatura relacionada o al desgaste patológico de las piezas dentarias. Existen muchos métodos para medir la dimensión vertical, entre los cuales el método antropométrico y el método craneométrico de Knebelman mostraron ser los más vinculados con el biotipo facial. El objetivo de este estudio fue comparar datos registrados con ambos métodos. La comparación fue realizada mediante un estudio de diseño transversal descriptivo con un total de 200 pacientes, usando un calibrador vernier para realizar mediciones entre puntos faciales establecidos. Los resultados fueron analizados por medio de la prueba de t de Student para datos emparejados estableciendo el nivel de significación en P<0,05. No se encontró diferencia significativa entre los métodos, pero el método de Knebelman mostró generar menos variabilidad en sus medidas. Este último método parece proporcionar más confiabilidad para su aplicación en la determinación de la dimensión vertical oclusal en todos los biotipos faciales estudiados.

Estimation of the Plastic Zone in Fatigue via Micro-Indentation.

Accurate knowledge of the plastic zone of fatigue cracks is a very direct and effective way to quantify the damage of components subjected to cyclic loads. In this work, we propose an ultra-fine experimental characterisation of the plastic zone based on Vickers micro-indentations. The methodology is applied to different compact tension (CT) specimens made of aluminium alloy 2024-T351 subjected to increasing stress intensity factors. The experimental work and sensitivity analysis showed that polishing the surface to #3 µm surface finish and applying a 25 g-force load for 15 s produced the best results in terms of resolution and quality of the data. The methodology allowed the size and shape of both the cyclic and the monotonic plastic zones to be visualised through 2D contour maps. Comparison with Westergaard's analytical model indicates that the methodology, in general, overestimates the plastic zone. Comparison with S355 low carbon steel suggests that the methodology works best for alloys exhibiting a high strain hardening ratio.

Therapeutic Approaches in Lysosomal Storage Diseases.

Lysosomal Storage Diseases are multisystemic disorders determined by genetic variants, which affect the proteins involved in lysosomal function and cellular metabolism. Different therapeutic approaches, which are based on the physiologic mechanisms that regulate lysosomal function, have been proposed for these diseases. Currently, enzyme replacement therapy, gene therapy, or small molecules have been approved or are under clinical development to treat lysosomal storage disorders. The present article reviews the main therapeutic strategies that have been proposed so far, highlighting possible limitations and future perspectives.

Tartrolon D, a cytotoxic macrodiolide from the marine-derived actinomycete Streptomyces sp. MDG-04-17-069.

Exploration of marine-derived actinomycetes as a source of antitumor compounds has led to the isolation of a new member of the tartrolon series, tartrolon D (4). This new compound was obtained from Streptomyces sp. MDG-04-17-069 fermentation broths and displayed strong cytotoxic activity against three human tumor cell lines. Additionally, the known compound ikarugamycin (5) was also found in the culture broths of the same microorganism. The structure of this new tartrolon was established by a combination of spectroscopic techniques (1D and 2D NMR, HRMS, and UV) as well as by comparison with published data for similar compounds.

Vertical Dimension of Occlusion: A comparative study between Anthropometric and Knebelman's craniometric methods / Dimensión vertical oclusal: un estudio comparativo entre el método antropométrico y el método craneométrico de Knebelman

ABSTRACT The masticatory system changes as time passes. The vertical dimension of occlusion (VDO) undergoes alterations due to temporomandibular joint disorders which in turn may be caused by related muscle modifications or pathological tooth wear. There are many methods to measure VDO. Among these, the anthropometric method and Knebelman's craniometric method have been shown to be the most closely related to facial biotype. The aim of this study was to compare data recorded with those two methods. A descriptive cross-sectional study was performed with a total 200 patients. A vernier caliper was used to measure facial landmarks. Results were analyzed using paired t-test, setting the level of significance at p<0.05. There was no significant difference between the two methods but Knebelman's method had less variability. Results suggest that Knebelman's method should provide more reliability for determining VDO in all the facial biotypes studied.

RESUMEN El sistema masticatorio cambia con el paso del tiempo. La dimensión vertical oclusal sufre alteraciones que se atribuyen a trastornos temporomandibulares a su vez causados por modificaciones en la musculatura relacionada o al desgaste patológico de las piezas dentarias. Existen muchos métodos para medir la dimensión vertical, entre los cuales el método antropométrico y el método craneométrico de Knebelman mostraron ser los más vinculados con el biotipo facial. El objetivo de este estudio fue comparar datos registrados con ambos métodos. La comparación fue realizada mediante un estudio de diseño transversal descriptivo con un total de 200 pacientes, usando un calibrador vernier para realizar mediciones entre puntos faciales establecidos. Los resultados fueron analizados por medio de la prueba de t de Student para datos emparejados estableciendo el nivel de significación en P<0,05. No se encontró diferencia significativa entre los métodos, pero el método de Knebelman mostró generar menos variabilidad en sus medidas. Este último método parece proporcionar más confiabilidad para su aplicación en la determinación de la dimensión vertical oclusal en todos los biotipos faciales estudiados.

[Training degree assessment of staff producing parenteral nutrition in Pharmacy Services]. / Evaluación del grado de formación del personal que elabora las nutriciones parenterales en los Servicios de Farmacia.

OBJECTIVE: To assess the level of expertise of Pharmacy personnel in the manufacturing of total parenteral nutrition. MATERIAL AND METHODS: An on-line survey including 17 questions concerning key aspects of TPN manufacturing was designed. Survey monkey software was used to create the survey and to analize its results. RESULTS: 135 answers were received. 95% of the participant Pharmacy services had written standard manufacturing procedures. 67% answered that phosphate salts should be the first electrolite to be additioned into the total parenteral nutrition and 34% affirmed that validation of the aseptic manufacturing technique was not performed. As far as personnel training was concerned, 19% of respondents had not received any specific training, although 99% considered it would be necessary to receive it. CONCLUSIONS: The polled personell has an acceptable level of expertise but adequate training courses are still necessary and should be promoted from Pharmacy services.

Objetivo: Evaluar el grado de formación del personal que elabora nutrición parenteral en los Servicios de Farmacia. Material y métodos: Se diseñó una encuesta on-line con 17 preguntas en la que se incluyeron los puntos más importantes en la elaboración de nutriciones parenterales. Para el diseño de la encuesta y el análisis posterior se utilizó la aplicación informática Survey monkey®. Resultados: Se obtuvieron un total de 135 respuestas. En el 95% de los Servicios de Farmacia existían normas escritas de elaboración. El 67% contestó que el fosfato se debía añadir cuando se empiezan a añadir los electrolitos y el 34% que no se realizaba la validación de la técnica aséptica de elaboración. En cuanto a la formación, el 19% no la había recibido, considerando necesario recibirla el 99%. Conclusiones: El personal encuestado presenta un grado de formación aceptable, pero son necesarios los cursos de formación que se deben fomentar desde los Servicios de Farmacia.

Absolute quantification in dopaminergic neurotransmission SPECT using a Monte Carlo-based scatter correction and fully 3-dimensional reconstruction.

UNLABELLED: Dopamine transporter (DAT) ligands have been developed for in vivo imaging of the dopaminergic system in SPECT. Although the visual analysis of SPECT images is, in general, suitable for clinical assessment, the accurate quantification of the striatal uptake might increase the sensitivity of the technique and help in the early diagnosis, follow-up, and eventual treatment response of Parkinson's disease (PD). This work is focused on assessment of the quantification of specific uptake of (99m)Tc-DAT ligands when compensation for all degrading phenomena is performed. METHODS: The SimSET Monte Carlo (MC) code was used to generate a set of SPECT projections of a numeric striatal phantom with different specific uptake ratios (SURs). An absolute quantification method (AQM), which performs a MC-based scatter compensation and a fully 3-dimensional (3D) reconstruction, was implemented. The scatter estimate was included in the reconstruction algorithm. RESULTS: The use of attenuation, point-spread-function (PSF), and scatter corrections resulted in an improvement in the value of the SUR of 37% on average with respect to the reconstruction without corrections. The magnitude of each improvement corresponded to 7% for the attenuation correction, 12% for the PSF correction using a 2-dimensional reconstruction algorithm and a further 11% for the PSF correction using a 3D reconstruction algorithm, and 7% for the scatter correction. CONCLUSION: Our findings indicate that the PSF correction plays a major role in the quantification of striatal uptake in comparison with the attenuation correction and the scatter correction. The implemented method also provides an absolute quantification procedure based on MC methods that do not depend on empiric approximations. The relative quantification results using the proposed AQM accounted for 96%-97% of the nominal SUR, whereas the limit achieved using only primary photons attained 98%-99%. The volumetric activity values obtained using the AQM converged toward the nominal values.

Aspectos socio demográficos y calidad de vida en salud Bucal, del personal del municipio de Azogues - Ecuador / Socio-demographic aspects and quality of life in oral health of the staff of the municipality of Azogues - Ecuador

Objetivo: Asociar los aspectos socio demográficos y la calidad de vida en salud bucal del personal del Municipio de Azogues - Ecuador. Material y métodos: La presente constituye una investigación transversal, descriptiva, observacional misma que investigó a 185 adultos, aplicándoles una encuesta para determinar aspectos relacionadas a datos personales, determinantes sociales y uso de servicio odontológico. Seguido se indagó sobre el impacto de la salud bucal en la calidad de vida utilizando el cuestionario validado Ohip -14Sp. Se efectúo análisis univariado y bivariado. Para el estudio bivariado se utilizó el Odds Ratio (OR) para asociar los factores mencionados con la calidad de vida relacionada a la salud bucal (CVRSB). Se contó con un nivel de confianza del 95% y un p<0,05. Resultados: No se encontró asociación estadísticamente significativa al evaluar todas las variables con CVRSB; el grupo con la mayor prevalencia de impactos según el nivel de instrucción fueron Universitarios con un 46%; según el ingreso mensual, los de ingreso mensual menor a $1000 con un 66%; de acuerdo a la denominación laboral los trabajadores con un 53%; de acuerdo al motivo de consulta, fueron otras causas 39%. Sin embargo, a pesar de que no hay una asociación significativa, se puede apreciar que el sexo masculino fue el más impactado. Conclusiones: Las determinantes sociales y CVRSB no estuvieron asociados. Las dimensiones limitación funcional, dolor físico y obstáculos fueron las más frecuentes.

Objective: To associate the socio-demographic aspects and the quality of life in oral health of the personnel of the Municipality of Azogues - Ecuador. Material and methods: This is a transversal, descriptive, observational research that investigated 185 adults, applying a survey to determine aspects related to personal data, social determinants and use of dental service. Afterwards, the impact of oral health on the quality of life was investigated using the Ohip-14Sp validated questionnaire. Univariate and bivariate analyzes were carried out. For the bivariate study, the Odds Ratio (OR) was used to associate the aforementioned factors with the quality of life related to oral health (HRQOL). There was a confidence level of 95% and p <0.05. Results: No statistically significant association was found when evaluating all variables with CVRSB; The group with the highest prevalence of impacts according to the level of education were University students with 46%; according to the monthly income, the monthly income less than $ 1000 with 66%, according to the labor denomination the workers with 53%; according to the reason for consultation, other causes were 39%. However, although there is no significant association, it can be seen that the male sex was the most impacted. Conclusions: The social determinants and CVRSB were not associated. The dimensions of functional limitation, physical pain and obstacles were the most frequent.