The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

The usability of daytime and night-time heart rate dynamics as digital biomarkers of depression severity.

BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Improvement of photocatalytic activity in the degradation of 4-chlorophenol and phenol in aqueous medium using tin-modified TiO2 photocatalysts.

In this work, we present the synthesis of TiO2 photocatalysts modified with different % mol of tin using the sol-gel method. The materials were characterized using different analytical techniques. The Rietveld refinement, XPS, Raman and UV-Vis techniques confirm the substitution of tin in the TiO2 structural lattice due to changes in crystal lattice parameters, the low-energy shift of the Sn 3d5/2 orbital, generation of oxygen vacancies and the decreased band gap and increased BET surface area. The material with 1 mol% tin shows superior catalytic activity compared to the references for the degradation of 40 ppm 4-chlorophenol (3 hours of reaction) and 50 ppm phenol (6 hours of reaction). Reactions fit pseudo first order kinetics in both instances. The increase in photodegradation efficiency was attributed to the generation of energy levels below the TiO2 conduction band caused by the incorporation of 1% mol of tin, oxygen vacancies, and the heterojunction formed between the brookite-anatase-rutile, causing inhibition of the recombination of the electron (e-) and hole (h+) photogenerated species. The easy synthesis, low cost and increased photodegradation efficiency of the photocatalyst with 1 mol% tin have the potential to favor the remediation of recalcitrant compounds in water.

Eficacia del ejercicio terapéutico en el síndrome del ovario poliquístico. Una revisión sistemática / Efficacy of therapeutic exercise in polycystic ovary syndrome. A systematic review

El síndrome del ovario poliquístico es uno de los problemas hormonales más frecuentes en mujeres en edad reproductiva. Este síndrome presenta gran cantidad de síntomas como desorden hormonal, ciclos menstruales irregulares o amenorrea, presencia de masas en los ovarios, aumento de peso, hirsutismo, acné, infertilidad, entre otros síntomas de hiperandrogenismo. El ejercicio físico ha sido pautado principalmente en estas mujeres con el objetivo de pérdida de peso; sin embargo, sería interesante conocer los efectos del ejercicio no solo en la pérdida de peso. Por ello el objetivo de esta revisión sistemática es conocer los efectos que produce el ejercicio terapéutico en las mujeres que presenta el SOP en aspectos como los cambios hormonales y el ciclo menstrual y otras alteraciones metabólicas. Para ello se realizó una busca bibliográfica en el mes de febrero del 2021 en las bases de datos CINAHL, Medline y PubMed. Empleándose los términos Medical Subject Heading (MeSH): «Exercise therapy», «Polycystic Ovary Syndrome» y «Therapeutic Exercise». Se incluyeron ensayos clínicos publicados en los últimos 10 años en idioma español o inglés. Tras la aplicación de los criterios de exclusión, resultaron 10 ensayos clínicos para su análisis. En la mayoría de las publicaciones se utilizan el ejercicio aeróbico y el ejercicio de resistencia progresiva, comprobando cuáles son los efectos que se consiguen al final del tratamiento. Se observó una mejora en los parámetros antropométricos y hormonales.Tras el análisis de los diferentes resultados de esta revisión, se puede concluir que el ejercicio terapéutico tiene efectos beneficiosos en el síndrome del ovario poliquístico, especialmente en el nivel hormonal y el ciclo menstrual.(AU)

Polycystic ovary syndrome is one of the most frequent hormonal problems in women of reproductive age, this syndrome presents many symptoms such as hormonal disorders, irregular menstrual cycles or amenorrhea, presence of masses in the ovaries, weight gain, hirsutism, acne, infertility, among other symptoms of hyperandrogenism. Physical exercise has been prescribed in these women with the aim of weight loss; however, it would be interesting to know the effects of exercise other than on weight loss. Therefore, the objective of this work is to know the effects that therapeutic exercise produces in women with this syndrome. A bibliographic search was conducted in February 2021 in the CINAHL, Medline and PubMed databases. Using the terms Medical Subject Heading (MeSH): “Exercise therapy”, “Polycystic Ovary Syndrome”, and “Therapeutic Exercise”. Clinical trials published in the last 10 years in Spanish or English were included. After application of the exclusion criteria, 10 clinical trials resulted from the analysis. In most of the publications, aerobic exercise and progressive resistance exercise are used, verifying the effects that are achieved at the end of the treatment. An improvement in anthropometric and hormonal parameters was observed.After analysing the different results of this review, we can conclude that therapeutic exercise has a benefit in polycystic ovary syndrome, especially for hormonal levels and the menstrual cycle.(AU)

Characterization of the hierarchical architecture and micromechanical properties of walnut shell (Juglans regia L.).

In the present work a comprehensive characterization of the hierarchical architecture of the walnut shell (Juglans regia L.) was carried out using scanning electron microscopy (SEM), atomic force microscopy (AFM) and confocal laser scanning microscopy (CLSM). Furthermore, micromechanical properties (hardness, HIT and elastic modulus, EIT) of plant tissues were evaluated at cell wall level by applying the instrumented indentation technique (IIT). The complex architecture of the material was described in terms of four hierarchical levels (HL): endocarp (H1), plant tissues (H2), plant cells (H3) and cell wall (H4). Our findings revealed that the walnut shell consists of a multilayer structure (sclerenchyma tissue, ST; interface tissue, IT; porous tissue, PT; and flattened parenchyma tissue, FPT), where differences in the microstructure and composition of plant tissues generate parallel gradients along the cross-section. The indentation tests showed a functional gradient with a sandwich-like configuration, i.e., a lightweight and soft layer (PT, HIT = 0.04 GPa) is located between two dense and hard layers (ST, HIT = 0.33 GPa; FPT, HIT = 0.28 GPa); where additionally there is an interface between ST and PT (IT, HIT = 0.16 GPa). This configuration is a successful strategy designed by nature to improve the protection of the kernel by increasing the strength of the shell. Therefore, the walnut shell can be considered as a functionally graded material (FGM), which can be used as bioinspiration for the design of new functional synthetic materials. In addition, we proposed some structure-property-function relationships in the whole walnut shell and in each of the plant tissues.

Vascular compression syndromes: the value of Doppler ultrasonography.

Vascular compression syndromes arise when a vessel in a tight anatomic space is entrapped by another structure, resulting in diverse symptoms for which different imaging tests are used to diagnose. Radiologists need to be familiar with vascular compression syndromes and to be able to identify their most representative findings. This paper aims to review the principal symptoms of vascular compression, describing and illustrating the key findings on Doppler ultrasonography that enable accurate diagnosis and guide further workup, avoiding unnecessary invasive tests and pointing to the appropriate treatment.

Síndromes de compresión vascular. Valor de la ecografía Doppler / Vascular compression syndromes: the value of Doppler ultrasonography

Los síndromes de compresión vascular consisten en el atrapamiento de un vaso por otra estructura en un espacio anatómico reducido, lo que provoca sintomatología diversa y para cuyo diagnóstico se emplean diferentes pruebas de imagen. Es importante familiarizarse con este tipo de patología y ser capaces de identificar sus hallazgos más representativos. El objetivo de este artículo es revisar los principales síndromes de compresión vascular, aportando datos clave de hallazgos en la ecografía Doppler que permitan establecer un diagnóstico acertado, evitar otras pruebas más agresivas o seleccionar aquellos pacientes que las requieran y orientar el tratamiento adecuado.(AU)

Vascular compression syndromes arise when a vessel in a tight anatomic space is entrapped by another structure, resulting in diverse symptoms for which different imaging tests are used to diagnose. Radiologists need to be familiar with vascular compression syndromes and to be able to identify their most representative findings. This paper aims to review the principal symptoms of vascular compression, describing and illustrating the key findings on Doppler ultrasonography that enable accurate diagnosis and guide further workup, avoiding unnecessary invasive tests and pointing to the appropriate treatment.(AU)

Effect of calcium oxalate crystals on the micromechanical properties of sclerenchyma tissue from the pecan nutshell (Carya illinoinensis).

The objective of this study was to evaluate the effect of the presence of calcium oxalate (CaOx) crystals on the micromechanical properties of sclerenchyma tissue from the pecan nutshell (Carya illinoinensis). The microstructure of the cross-section nutshell was examined using light microscopy (LM) and atomic force microscopy (AFM). Using an instrumented indentation system, indentation tests with maximum loads of 500 mN were made on the biological material where the variables studied were the number of crystals present in the evaluated area and the size of individual crystals. Microscopic analysis revealed that the pecan nutshell consists of sclerenchyma tissue with multiple CaOx crystals randomly distributed throughout the material, exhibiting prismatic shapes and various sizes. The results of the indentation tests showed that the examined areas where there were crystals (1, 2 or up to 3) presented values of hardness and elastic modulus significantly higher (P < 0.05) compared to the sclerenchyma (without crystals). Likewise, there were no significant differences (P > 0.05) between the values of the micromechanical properties of the areas evaluated as a function of the number of crystals. On the other hand, it was observed that the size of the crystals did not show a direct correlation with the mechanical properties evaluated as expected. In conclusion, the biomineralization phenomenon is a successful strategy designed by nature to improve the rigidity of the pecan nutshell, where the CaOx crystals strengthen the structure by increasing the micromechanical properties.

Comparison of the third molar maturity index (I3M) between left and right lower third molars to assess the age of majority: a multi-ethnic study sample.

The diagnostic accuracy of the I3M to assess the legal age of 18 years has already been tested in several specific-population samples. The left lower third molar has been extensively used for discriminating between minors and adults. This research aimed to compare the usefulness of lower third molar maturity indexes, from both left and right side (I3ML and I3MR), in samples originating from four distinct continents in order to examine possible differences in their accuracy values. For this purpose, a sample of 10,181 orthopantomograms (OPGs), from Europe, Africa, Asia and America, was analysed and previously scored in other studies. The samples included healthy subjects with no systemic disorders with both third molars and clear depicted root apices. Wilcoxon Signed Rank test for left and right asymmetry did not show any significant differences. Data about sensitivity, specificity, predictive values, likelihood ratio and accuracy were pooled together and showed similar results for I3ML and I3MR, respectively. In addition, all these quantities were high when only the I3MR was considered to discriminate between adults and minors. The present referable database was the first to pool third molar measurements using panoramic radiographs of subjects coming from different continents. The results highlighted that both I3ML and I3MR are reliable indicators for assessing the legal age of 18 years old in those jurisdictions where this legal threshold has been set as the age of majority.

Organized breast cancer screening not only reduces mortality from breast cancer but also significantly decreases disability-adjusted life years: analysis of the Global Burden of Disease Study and screening programme availability in 130 countries.

BACKGROUND: Multiple studies over the past 4 decades have shown the significant benefit of breast cancer screening (BCS) in reducing mortality rates from breast cancer (BC). However, significant debate exists about the role of BCS in this regard, with some studies also showing no benefit in terms of mortality along with issues such as overdiagnosis, health care utilisation costs, psychological distress or overtreatment. To date, no BCS study has focused on disability. Hence the aim of this study is to evaluate the relative contribution of BCS approaches to age-standardized mortality and disability-adjusted life years (DALYs) rates along with other related risk factors, from a country-level perspective. PATIENTS AND METHODS: This study created a country-dataset by merging information from the Global Burden of Disease study regarding female age-standardized BC mortality, DALYs rates and other risk factors with the BCS programme availability at the national or regional level (versus no or only pilot such programme), BCS type (mammography, digital screening, breast self-examination and clinical breast examination) and other BCS-related information among 130 countries. Mixed-effect multilevel regression models were run to examine the associations of interest. RESULTS: The most important factor predictive of lower mortality was the more advanced type of BCS programme availability [mammography: -4.16, 95% CI -6.76 to -1.55; digital mammography/ultrasound: -3.64, 95% CI -6.59 to -0.70] when compared with self- or clinical breast examinations. High levels of low-density lipoprotein cholesterol (LDL-c) and smoking were also related to higher mortality and DALYs from BC. In terms of BC DALYs, BCS had a 21.9 to 22.3-fold increase in the magnitude of effect compared with that in terms of mortality. Data on mortality and DALYs in relation to BCS programmes were also calculated for high-, middle- and low-income countries. CONCLUSIONS: These data further support the positive effects of BCS in relation to age-standardized BC mortality rates, and for the first time show the impact of BCS on DALYs too. Additional factors, such as diabetes, high levels of LDL-c or smoking seemed to be related to BC mortality and disability, and could be considered as additional components of possible interventions to be used alongside BCS to optimize the BCS benefit on patients.

Microhemorragias cerebrales múltiples asociadas con el desarrollo de coagulación intravascular diseminada / Multiple cerebral microbleeds associated with disseminated intravascular coagulation

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A full Bayesian calibration model for assessing age in adults by means of pulp/tooth area ratio in periapical radiography.

The Bayesian approach is being a fundamental tool in forensic and legal field where inferences and decisions are made. In this study, a full Bayesian calibration model was developed to make probabilistic inferences about age estimation in a reference sample of 891 periapical X-rays of upper and lower canines. These teeth belonged to both deceased and living adult subjects, aged between 20 and 86 years, coming from five different countries (Turkey, Italy, Portugal, Japan and Mexico). For this purpose, the narrowing of pulp chamber due to the apposition of secondary dentine was analysed by means of the pulp/tooth area ratio. To determine the agreement of the method, intra- and inter-observer differences for measuring process were calculated by means of the intraclass correlation coefficient (ICC) analysis. Observer error tests showed excellent agreement between observers and between repeated assessments. According to the results of the ANCOVA, neither nationality nor sex was associated to the secondary dentine apposition while it is associated with individual's age. The results of the present study indicated that the concept of probability is intrinsically linked to the assessment of age in a forensic context, and the Bayesian approach could be considered a robust tool to overtake the bias generated by traditional regression models, thus helping the decision-making process in a legal framework.

Síndrome CLIPPERS. A propósito de un caso / CLIPPERS syndrome: A case report

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Neumotórax espontáneo primario, ¿dónde podemos mejorar? / Primary spontaneous pneumothorax, room for improvement

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Sequential pretreatment to recover carbohydrates and phosphorus from Desmodesmus sp. cultivated in municipal wastewater.

This study focused on the simultaneous recovery of carbohydrates (CHO) and phosphorus (P) from Desmodesmus sp. biomass cultivated in municipal wastewater, through a sequential pretreatment. The pretreatment consisted first of ultrasound to trigger cell disruption followed by ozonation to recover CHO and P. For ozone pretreatment, three different parameters were considered: ozone concentration (9, 15, 21, 27, 36, and 45 mg O3/L), contact time (15, 25 and 35 min), and pH (8 and 11). The maximum simultaneous release of 84% of CHO and 58% of P was achieved at the experimental parameters of ozone concentration of 45 mg O3/L, contact time of 35 min, and pH of 11. Also, P was concentrated in solution by 8- to 14-fold with respect to municipal wastewater. The sequential pretreatment was conducted at alkaline pH of 11 and atmospheric conditions, which may considerably reduce energy demand and reagents, in comparison to a traditional hydrolysis pretreatment. The results found suggest that the sequential pretreatment could be feasible on a large scale.

Intensified recovery of lipids, proteins, and carbohydrates from wastewater-grown microalgae Desmodesmus sp. by using ultrasound or ozone.

This study evaluates the effect of ultrasound and ozone pretreatments for the subsequent recovery of Desmodesmus sp. biocomponents-lipids, proteins, and carbohydrates-using a response surface methodology. Both pretreatments impact on the recovered lipids quality, solvent waste production and extraction time is analysed for process intensification purposes. For ultrasound pretreatment, independent parameters were energy applied (50-200 kWh/kg dry biomass), biomass concentration (25-75 g/L), and ultrasonic intensity (0.32 and 0.53 W/mL). While for ozone pretreatment, independent parameters were ozone concentration (3-9 mg O3/L), biomass concentration (25-75 g/L), and contact time (5-15 min). In the case of ultrasound pretreatment, recovery yield reached 97 ±â€¯0.4%, 89 ±â€¯3%, and 73 ±â€¯0.6% for proteins, carbohydrates and lipids respectively. Given process required: energy applied of 50 kWh/kg dry biomass, 75 g/L of biomass concentration, 0.32 W/mL of ultrasonic intensity, and 56 min of time process. Ultrasound caused high cell disruption releasing all proteins, thereby obviating downstream processing for its recovery. Ozone pretreatment recovery yield was 85 ±â€¯2%, 48 ±â€¯1.4%, and 25 ±â€¯1.3%, for carbohydrates, lipids and proteins respectively, under the following conditions: 9 mg O3/L of ozone concentration, 25 g/L of biomass concentration, and 5 min of contact time that depicts an energy consumption of 30.64 kWh/kg dry biomass. It was found that ultrasound and ozone pretreatments intensified the lysis and biocomponents recovery process by reducing solvent consumption by at least 92% and extraction time between 80% and 90% compared with extraction of untreated biomass biocomponents. Both pretreatments improve the composition of the recovered lipids. It was noted that the yield of neutral lipids increased from 28% to 67% for ultrasound pretreatment while for ozone pretreatment from 49% to 63%. The method used for lipid extraction may also have an effect but here it was kept constant.

Predictor of enhanced mortality in patients with multimorbidity and atrial fibrillation in an acute hospital setting.

BACKGROUND: Patients with atrial fibrillation (AF) admitted to hospital commonly have comorbidities. Few studies have attempted to determine factors prognostic of mortality in hospitalized AF patients with multimorbidity. AIM: To identify factors associated with mortality in hospitalized AF patients. DESIGN: Retrospective cohort study. METHODS: Patients with multimorbidity (≥2 chronic diseases), with or without AF, discharged from Lugo hospital (Spain) between 1 January 2000 and 31 December 2015. Data were extracted from hospital medical records. RESULTS: Of 74 220 patients (170 978 hospitalizations), 52 939 had multimorbidity (14 181 had AF; 38 758 no AF) and were included in our study. Patients with AF were older (mean ± standard deviation 78.6 ± 10.0 vs. 71.9 ± 14.2 years) and had a higher mortality rate (27.1 vs. 20.5%) than those without AF. Gender (female), age, stroke and congestive heart failure (CHF), but not AF, were independently associated with mortality. AF significantly increased the mortality risk in women [relative risk (RR) 1.091; 95% confidence interval (CI) 1.021-1.165; P = 0.010] and in those aged >80 years (RR 1.153; 95% CI, 1.1-1.2; P < 0.001). CHF independently increased the risk of mortality across all age groups (RR 1.496; 95% CI 1.422-1.574; P < 0.001). CONCLUSIONS: Hospitalized patients with AF have a higher mortality rate than those without AF. The prognostic significance of AF changes with age and gender while CHF is associated with the greatest risk of death.

Study of the porosity of calcified chicken eggshell using atomic force microscopy and image processing.

In this work, the porosity of the layers of calcified chicken eggshell (vertical crystal layer VCL, palisade layer PL and mammillary layer ML) was evaluated using atomic force microscopy (AFM) and image processing (IP). AFM topographic images were obtained from different locations for each layer and along the cross-section of calcified eggshell. Roughness parameters, surface area values, pore size and shape, surface porosity, area occupied by pores and pore density were obtained from AFM and IP. It was observed that the thickest layer (PL) exhibited the highest degree of porosity (surface porosity = 2.75 ± 1.68%, pore density = 162 ± 60 pores/µm2) when compared to the other two layers. In general, the pores located in all layers ("bubble pores") had circular shape and similar sizes. Measurements revealed a porosity gradient along the cross-section which varied with position, i.e., increasing surface porosity from the VCL towards the region of the PL closer to the ML, and decreasing surface porosity from this location towards the ML innermost surface. This suggests that the calcified eggshell has a sandwich-like structure where porosity may influence gas exchange and mechanical properties. The combination of AFM with IP presented here provides a simple and precise method to study porosity in calcified chicken eggshell, and this methodology could be used to examine other types of porous biological materials.