Green synthesis of gold nanoparticles via Moringa oleifera seed extract: antioxidant, antibacterial and anticarcinogenic activity on lung cancer.

Plant-mediated biosynthesis of nanoparticles is a green method that allows synthesis in one-pot process. Synthesis of gold nanoparticles with plant extracts has gained interest in the field of biomedicine due to its variety of applications. This study presents the synthesis via green chemistry of gold nanoparticles (AuNPs) using the methanol extract of Moringa oleifera seeds. The AuNPs were synthesized at room temperature. UV-Vis spectroscopy confirmed the formation of AuNPs by identifying the surface plasmon resonance located at 546 nm. TEM analysis shows spherical nanoparticles. FTIR analysis demonstrated the presence of specific bioactive molecules responsible for the Au3+ ion reduction process. The antioxidant activity of the nanoparticles was evaluated on the stabilization of the DPPH radical (1,1-diphenyl-2-picrylhydrazyl, 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl). The antimicrobial activity analysis was developed by broth microdilution method at different concentrations against Escherichia coli and Staphylococcus aureus. Minimum inhibitory concentration were 400 µg/mL and 200 µg/mL, respectively. A549 lung cancer cell proliferation was measured according to the MTT protocol, indicating a dose-dependent response and a IC50 of 163.9 ± 13.27 µg/mL. The AuNPs synthesized using M. oleifera seeds showed promise as active materials for antimicrobial or anticancer products.

Dynamic Nanoindentation and Short-Range Order in Equiatomic NiCoCr Medium-Entropy Alloy Lead to Novel Density Wave Ordering.

Chemical short-range order is believed to be a key contributor to the exceptional properties of multicomponent alloys. However, its direct validation and confirmation has been highly elusive in most compounds. Recent studies for equiatomic NiCoCr alloys have shown that thermal treatments (i.e., annealing and aging) may facilitate and manipulate such ordering. In this work, by using molecular simulations, we show that nanomechanical probes, such as nanoindentation, may be utilized toward further manipulation of chemical short-range order, providing explicit validation pathways. By using well established interatomic potentials, we perform hybrid molecular-dynamics-Monte Carlo at room temperature to demonstrate that particular dwell nanoindentation protocols can lead, through thermal Monte Carlo equilibration, to local reorganization under the indenter tip, toward a density-wave stripe pattern. We characterize the novel density-wave structures, which are highly anisotropic and dependent on local, nanoindentation-induced stress concentrations, and we show how they deeply originate from intrinsic features of interelemental interactions. Furthermore, we show that these novel patterns consistently scale with the incipient plastic zone, under the indenter tip, justifying their observation at experimentally feasible nanoindentation depths.

Manejo de extrusión forzada ortodóntica: Reporte de un caso / Management and Follow-up of Orthodontic Forced Extrusion: A Case Report

El presente caso clínico se enfoca en el diagnóstico y el tratamiento de erupción forzada en un paciente con trauma dental. Objetivo: Proponer una alternativa de tratamiento multidisciplinario el cual permita incrementar estructura dentaria a través de la extrusión forzada y posteriormente rehabilitarlo en función y estética. Métodos: Se describe el caso de un paciente adulto de 78 años de sexo masculino, sano y sin antecedentes patológicos, acude a la clínica de la Especialidad de Ortodoncia y Ortopedia Dentomaxilo facial, referido por un especialista en Endodoncia, debido a fractura corono-radicular de canino superior derecho, pilar de puente fijo de tres unidades En la exploración intraoral presenta fractura cervical de la corona del canino superior derecho. Como primer paso, se realizó tratamiento endodóntico en la pieza dentaria y colocación de un aditamento intraconducto de soporte (endoposte vaciado), con el objeto de mejorar la tracción ortodóntica. Este aditamento consistió en un poste colado con perforaciones. Se procede a colocar aparatología fija en la arcada superior con técnica MBT (slot 0.022), del molar derecho hasta el canino izquierdo de cementado indirecto y pasivo (con los slots de los brackets alineados). Inmediatamente después, se colocó un arco rectangular 0.019 x 0.025 de acero inoxidable con un doblez de extrusión a nivel del canino superior derecho. En el mismo doblez, se adaptó un loop tipo helix que funcionó como apoyo para colocar la ligadura pasiva (lace back). Resultados : El tratamiento realizado en este paciente es satisfactorio, coadyuvando en su estado de salud general mejorando su autoestima. Conclusión: Aquí se aprovecharon todas las ventajas que ofrece la extrusión ortodóntica forzada, incluso en un paciente adulto mayor, logrando una tracción de cuatro milímetros, que se consiguió gracias al empleo de fuerzas extrusivas ligeras y controladas sobre el órgano dentario afectado. Con la modalidad de tratamiento descrita se puede lograr un alargamiento de corona sin la necesidad de realizar una resección ósea, lo que permite una correcta rehabilitación protésica, devolviendo la función y estética al diente lesionado y brindando un beneficio integral al paciente.

The case of an adult patient with a complicated Crown fracture of the right upper canine due to trauma is reported, diagnosing a class VII Ellis coronal fracture. There are several treatment alternatives that range from the extraction, placement of a bone graft and placement of an implant, to a forced root extrusión with bone removal to allow the biological space and subsequently be restored. In the present case, a multidisciplinary orthodontic forced extrusion treatment is performed, which allows to increase the amount of clinical remnant, preserving the periodontal support and maintaining the biologic thickness, thus achieving to maintain the root remnant with good length so that prosthetic rehabilitation is facilitated. The clinical and radiographic follow-up was 12 months. The multidisciplinary treatment involved: Root canal treatment, forced extrusion with orthodontics, fibrotomy with root planing and fixed prosthesis.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study.

BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.

Practical recommendations for the clinical evaluation of patients with hereditary ataxia and hereditary spastic paraplegia.

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP.

Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection.

BACKGROUND: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. METHODS: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). DISCUSSION: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735445. Registered on 25 June 2019.

Role of the Interchangeable Cations on the Sorption of Fumaric and Succinic Acids on Montmorillonite and its Relevance in Prebiotic Chemistry.

It has been proposed that clays could have served as key factors in promoting the increase in complexity of organic matter in primitive terrestrial and extraterrestrial environments. The aim of this work is to study the adsorption-desorption of two dicarboxylic acids, fumaric and succinic acids, onto clay minerals (sodium and iron montmorillonite). These two acids may have played a role in prebiotic chemistry, and in extant biochemistry, they constitute an important redox couple (e.g. in Krebs cycle) in extant biochemistry. Smectite clays might have played a key role in the origins of life. The effect of pH on sorption has been tested; the analysis was performed by UV-vis and FTIR-ATR spectroscopy, X-ray diffraction and X-ray fluorescence. The results show that chemisorption is the main responsible of the adsorption processes among the dicarboxylic acids and clays. The role of the ion, present in the clay, is fundamental in the adsorption processes of dicarboxylic acids. These ions (sodium and iron) were selected due to their relevance on the geochemical environments that possibly existed into the primitive Earth. Different mechanisms are proposed to explain the sorption of dicarboxylic acids in the clay. In this work, we propose the formation of complexes among metal cations in the clays and dicarboxylic acids. The organic complexes were probably formed in the prebiotic environments enabling chemical processes, prior to the appearance of life. Thus, the data presented here are relevant to the origin of life studies.

Incubation period of COVID-19: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n=792) in the meta-analysis. The heterogeneity (I2 83.0%, p<0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2-6.0) to 6.7 days (95% CI: 6.0-7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods.

BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.

Consensus and recommendations on vaginal-cuff Brachytherapy of the Spanish Brachytherapy Groups of SEOR and SEFM.

PURPOSE/OBJECTIVE(S): On October 5, 2018, a meeting of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group was held, in collaboration with the Spanish Society of Medical Physics (SEFM), with the aim of preparing a consensus document on postoperative vaginal-cuff brachytherapy (VCBT). MATERIALS/METHODS: A survey including 42 questions was sent to Spanish Radiation Oncology Centres before the meeting. The survey items included: experience in VCBT, technique indications, previous patient preparation, applicator type, implant procedure, computerized tomography (CT) simulation, definition of target volumes and organs at risk (OAR), dose prescription, fractionation, treatment planning, dosimetric parameters and constraints to OAR. Thirty-three centres answered the survey. Statistical analysis of the survey considered that there was consensus when there was ≥ 85% of agreement related to a survey item, otherwise an item with < 85% of agreement would be discussed during the meeting to reach consensus. RESULTS: The results of the survey are reported here. The mean number of patients treated per centre in 2017 was 52 ± 41 (range 7-175), and the mean number of procedures per centre was 175 ± 150 (range 24-701).There was consensus on: the indications, applicator type, the OAR to be considered, the prescription point, standardisation and dosimetric quality parameters. There was no consensus on: patient preparation for the implant, the need for performing CT simulation and the frequency, the length of the vagina to be treated, if CTV should be delimited, the definition of the clinical target volume, fractionation, overall EQD2, active source length, separation between dwelling stepping source positions, if considering the uniformity/maximum values for dwelling stepping sources, the optimization mode, and the limiting doses to the OAR. After presenting the results of the survey, the consensus meeting discussion focused on the issues for which there was no consensus. CONCLUSION: A consensus document on postoperative VCBT of the Spanish Brachytherapy Groups of SEOR-SEFM was elaborated.

[Incubation period of COVID-19: A systematic review and meta-analysis]. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.