Expert Recommendations from the AEDV on Legal Aspects Surrounding the Management of Sexually Transmitted Diseases. / Recomendaciones de expertos de la AEDV sobre los aspectos legales en el manejo de las infecciones de transmisión sexual.

The incidence of sexually transmitted diseases has been on the rise in our setting for decades. These infections represent not only an individual problem, but also a problem of public health. Therefore, the management of STDs involves reducing community incidence, which means that common issues in the clinical practice such as failure to attend may become a more complex problem, which adds to the difficult and delicate task of locating sexual contacts that would benefit from screening and the appropriate treatment. On the other hand, STDs have direct legal implications in cases of underage patients, or suspected sexual assault. Therefore, the correct handling of these scenarios requires knowledge of the legal framework that regulates them. Dermatologists are clinically trained and prepared to deal with these conditions. Nonetheless, the legal issues involved are often difficult to solve. This document stands as a simple reference guide to help solve the main legal issues we may encounter in a consultation when dealing with STDs.

A comparative study on the functional outcomes of patients who underwent internal versus external fixation for Tibial Plateau fractures two years post-surgery

Introduction@#Tibial plateau fractures are due to high energy trauma brought about by axial compression forces and associated varus or valgus component. @*Objective@#Patients diagnosed with tibial plateau fractures from January to December 2018 treated with internal vs. external fixation will be described according to their Schatzker classification. The study further aims to compare the functional outcomes between the two groups in terms of surgery done. @*Methods@#A chart review determined the distribution of demographics. The Modified Rasmussen Score (MRS) was used to determine the clinical and radiographic parameters after taking a new knee radiograph and assessment from the rehabilitation department. The MRS determined the functional outcomes of the said patients. Ethical considerations and proper informed consent were upheld after being reviewed by the hospital’s research committee. @*Results@#Out of 48 patients, 35 underwent internal fixation via open reduction using plates and/or screws, while 13 underwent external fixation using hybrid external fixator. The demographic profile showed mostly males between ages 20 to 49 years old. Most cases were due to vehicular accidents affecting the left lower extremity. In terms of Schatzker classification, the most common was type VI. The computed mean MRS of the internal fixation group was 30.43 while the external fixation group was 30.00, generally showing no significant difference. @*Conclusion@#Surgical intervention of tibial plateau fractures aims for anatomic reduction using internal or external fixation. There was no significant difference on the functional outcome of the two groups despite classifying the respondents according to Schatzker type, hence we can conclude that external fixation be chosen as the treatment of choice for tibial plateau fractures when properly indicated.

COVID in Pediatric Age: an opinion paper.

The incidence of COVID in pediatrics was underestimated during the first months of the pandemic due to the oligosymptomatic nature of the infection in many children and the scarcity of diagnostic tests applied to this population. It is now accepted that children are infected and transmit the disease in the same way as adults. On the contrary, children have less severe and less lethal COVID, probably due to a lower maturity of the child's immune system, a lower number of ACE2 receptors and the lower presence of comorbidities in this population group. The development of a multisystemic inflammatory syndrome after SARS-CoV-2 infection in children, despite its rarity, is a very serious condition that frequently requires intensive care. Other less severe post-COVID manifestations have been described in children but are not yet well defined. COVID has had and continues to have a significant psychological impact on the children themselves, on their caregivers and on the exacerbation of pre-existing psychiatric conditions. We apply adult therapeutic principles to children but with very low levels of evidence. Information on the tolerability of the available medications in this population group is still scarce. The mortality of COVID in children is very low and generally affects children with significant comorbidities. There are, at present, three vaccines licensed for pediatric use which are compatible with all other vaccines applicable to children. In these circumstances, there has been much speculation about the indication for vaccination in the pediatric age group, but given its good tolerance, there are clinical and ethical reasons that, in our opinion, justify it.

Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions.

Genetic sensors with unique combinations of DNA recognition and allosteric response can be created by hybridizing DNA-binding modules (DBMs) and ligand-binding modules (LBMs) from distinct transcriptional repressors. This module swapping approach is limited by incompatibility between DBMs and LBMs from different proteins, due to the loss of critical module-module interactions after hybridization. We determine a design strategy for restoring key interactions between DBMs and LBMs by using a computational model informed by coevolutionary traits in the LacI family. This model predicts the influence of proposed mutations on protein structure and function, quantifying the feasibility of each mutation for rescuing hybrid repressors. We accurately predict which hybrid repressors can be rescued by mutating residues to reinstall relevant module-module interactions. Experimental results confirm that dynamic ranges of gene expression induction were improved significantly in these mutants. This approach enhances the molecular and mechanistic understanding of LacI family proteins, and advances the ability to design modular genetic parts.

Rumination syndrome. A review article. / Síndrome de rumiación. Artículo de revisión.

Rumination syndrome is a functional gastrointestinal disorder characterized by effortless postprandial regurgitation of ingested food into the mouth. An unperceived postprandial contraction of the abdominal wall could be a key mechanism. In those patients, retrograde flow of the ingested gastric content into the mouth is produced due to a simultaneous combination of elevated intra-abdominal pressure and negative intrathoracic pressure. The estimated prevalence is around 2% in the general adult population. The main clinical characteristics include: a) early postprandial regurgitation, b) the effortlessly regurgitated material is similar to the ingested food, c) the regurgitated material is spit out or swallowed again. The clinical diagnosis of rumination syndrome relies on the clinical criteria. High resolution esophageal manometry, ideally including impedance monitoring, can be an important adjunct for making the clinical diagnosis. Its management is based on instruction as to the nature of the pathology, education in postprandial diaphragmatic breathing, and the assessment of possible psychiatric comorbidity. Baclofen use is reserved for second-line treatment in patients with refractory symptoms.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Microwave-Assisted Extraction of Pectin from "Saba" Banana Peel Waste: Optimization, Characterization, and Rheology Study.

One way to valorize "Saba" banana peel waste is to extract high-value compounds, such as pectin, and use it for food applications. In this study, the parameters for the microwave-assisted extraction of pectin were screened and optimized using Response Surface Methodology. The pectin was purified and then subjected to characterization. Results showed that the optimum extraction conditions were 195°C, 8% solid-liquid ratio, and pH 3 hydrochloric acid (HCl), with predicted and actual yields of 12.8% and 14.2%, respectively. The subsequent purification method increased the purity of pectin by 300%. The pectin was found to be low-methoxy in nature and had an average particle size of 300 nm. The pectin application in whey protein isolate resulted in a shear-thinning fluid, with an improved viscosity compared to a control. When applied to a commercial orange juice, the in vitro digestion study showed that the fluid's viscosity was higher before and during the gastric and intestinal digestion at the low physiological shear rate.

Food waste management during the COVID-19 outbreak: a holistic climate, economic and nutritional approach.

Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the "strong fluctuations and short-term changes" on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (-8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.

Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy.

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and ligand response properties of MphR, which is able to control gene expression in response to a molecular signal in cells. Furthermore, we studied molecular interactions between the TetR DNA-binding module and MphR ligand-binding module by using mutant analysis. Together, we demonstrated that TetR family regulators contain discrete and functional modules that can be used to build biological components with novel properties. This work highlights the utility of rational design as a means of creating modular parts for cell engineering and introduces new possibilities in rewiring cellular response pathways.

Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.

Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information.

Regionalizing eco-toxicity characterization factors for copper soil emissions considering edaphic information for Northern Spain and Portuguese vineyards.

The management of vineyards depends on the use of plant protection agents. Regardless of the numerous environmental impacts that these pesticides generate during their production, their dosage as pest control agents in vineyards causes an important toxic effect that must be monitored. Copper-based inorganic pesticides are the most widely used agents to control fungal diseases in humid wine-growing regions. It is, however, significant that the environmental analysis of their use through the Life Cycle Assessment (LCA) methodology does not provide detailed information on the potential toxicity of this type of pesticides. Hence, most studies report average values for copper characterization factors (CFs), excluding local soil characteristics. The objective of the study was the spatial characterization of the ecotoxicity factors of copper soil emissions as a function of the chemical characteristics of vineyard soils located in Portugal and Galicia (NW Spain). A multiple linear regression model was applied to calculate the comparative toxic potential. Subsequently, CFs for copper were calculated based on spatial differentiation considering the variable properties of the soil within each wine appellation. The CFs obtained for the area evaluated ranged from 141 to 5937 PAF·m3·day/kgCu emitted, for fibric histosols (HSf) and dystic cambisols (CMd), respectively. Moreover, the average values obtained for Galician and Portuguese soils were 1145 and 2274 PAF·m3·day/kgCu emitted, respectively. The results obtained illustrate the high variability of CF values as a function of the chemical characteristics of each type of soil. For example, Cu soil mobility was linked to organic carbon content and pH. Finally, to validate the representativeness of the calculated CFs, these were applied to the results of 12 literature life cycle inventories of grape production in the area evaluated, revealing that impact scores associated with Cu emissions can considerably vary when spatially-differentiated CFs are implemented.

Regeneration of a keystone semiarid shrub over its range in Spain: habitat degradation overrides the positive effects of plant-animal mutualisms.

Global change drivers are currently affecting semiarid ecosystems. Because these ecosystems differ from others in biotic and abiotic filters, cues for plant regeneration and management derived from elsewhere may not be applicable to semiarid ecosystems. We sought to determine the extent to which regional variation in regeneration prospects of a long-lived semiarid keystone shrub depends on anthropogenic habitat degradation, plant-animal interactions and climate determinants. We investigated the regeneration ability (via population size structure, juvenile density and juvenile/adult ratio), fruit set and seed dispersal of Ziziphus lotus in 25 localities spanning the range of its threatened habitats in Spain. We dissected the relative contribution of different regeneration determinants using multiple regression and structural equation modelling. Population regeneration was extremely poor, and size structures were biased towards large classes and low juvenile densities and juvenile/adult ratios. Poor regeneration was often coincident with seed dispersal collapse. However, the positive effect of seed dispersal on population regeneration disappeared after considering its relationship with habitat degradation. Protected areas did have juveniles. Together, these data suggest that habitat degradation directly impacts juvenile establishment. Our results provide insights into habitat and species management at the regional level. Z. lotus populations are currently driven by persistence-based dynamics through the longevity of the species. Nonetheless, collapsed seed dispersal, poor regeneration and the removal of adults from their habitats forecast extinction of Z. lotus in many remnants. The extreme longevity of Z. lotus provides opportunities for recovery of its populations and habitats through effective enforcement of regulations.

[Treatment of encephalopathy by means of valproic acid with carglumic acid. Reply]. / Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

TITLE: Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

[Cognitive impairment as a predictor of functional decline after hospitalization: DECOFIRH Study]. / Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.

AIM: Cognitive impairment is underdiagnosed in the elderly. We aimed to study the rate of positive responses to an informant-based questionnaires and functional disability after hospital discharge. PATIENTS AND METHODS: Observational prospective case series of patients aged 70-85 years-old admitted for hospitalization in an Internal Medicine ward. All medical records were reviewed and those patients with no previous diagnosis of dementia or related neurological conditions, no previous recent hospitalization or not having a caregiver were evaluated after signing an informed consent. A medical interview including the Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained three months after discharge. RESULTS: During a 3-month period a total of 809 admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's mean age was 80 years-old. Common comorbidities were arterial hypertension (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent cause of admission was infectious disease (37.9%). Test positivity for cognitive impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the patients were functionally independent. At three months this percentage dropped to 24%. CONCLUSIONS: In this small sample size, almost a third of older patients, without major comorbidities or neurological disorders, admitted to a general hospital showed an informant-based suggestion of cognitive impairment previously undiagnosed. Functional impairment affects almost a quarter of these patients three months after admission.

TITLE: Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.Objetivo. El deterioro cognitivo esta infradiagnosticado. El estudio DECOFIRH pretende detectar la tasa de deterioro cognitivo no conocido y su impacto en la situacion funcional de estos pacientes tras un ingreso hospitalario mediante cuestionarios realizados a un informador. Pacientes y metodos. Estudio observacional prospectivo realizado sobre una serie de casos, de pacientes comprendidos entre 70 y 85 años, que ingresan en el Servicio de Medicina Interna de un hospital terciario. Se excluyo a los pacientes con diagnostico de demencia o enfermedades neurologicas graves, asi como a los que habian sido hospitalizados recientemente. Los tests empleados en la deteccion de deterioro cognitivo fueron Alzheimer's Disease 8 (AD8) e Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Asimismo, se evaluo la situacion funcional mediante el indice de Barthel en el momento del ingreso y tres meses despues. Resultados. Durante los tres meses de seguimiento ingresaron 809 pacientes y cumplieron los criterios de inclusion 79 (9,7%) de ellos. Su edad media era de 80 años. Mediante el IQCODE se detecto una tasa de deterioro cognitivo del 30,3%, y con el AD8, del 34,1%. En el ingreso, el 37,9% de los pacientes era funcionalmente independiente. A los tres meses, este porcentaje cayo al 24%. Conclusiones. En nuestra muestra, casi un tercio de los ancianos sin comorbilidades sistemicas o neurologicas graves dio positivo para la deteccion de deterioro cognitivo segun nuestros tests basados en el informador, sin ser este conocido previamente. El deterioro funcional afecta casi a una cuarta parte de estos pacientes a los tres meses del ingreso.

[Treatment of encephalopathy by means of valproic acid with carglumic acid: two case reports and a review of the literature]. / Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.

INTRODUCTION: Valproic acid (VPA) is a drug mainly used to treat epilepsy. Hyperammonaemic encephalopathy due to VPA is a rare but serious complication. The mechanism by which VPA influences the increase in ammonia consists in blocking the urea cycle, thereby inhibiting N-acetylglutamate synthase and diminishing acetyl coenzyme A. Generally, the treatment employed has been to withdraw VPA and to administer arginine, carnitine, antibiotics, glucose and protein restriction. Previous experience with carglumic acid is limited to reports of isolated cases of paediatric patients. CASE REPORTS: We report the cases of two adult patients with encephalopathy due to VPA who were treated with carglumic acid, in addition to the conventional measures. Following treatment with the drug, ammonia levels can be seen to return to normal values. In one of the two cases, owing to the existence of another cause of encephalopathy, no clinical improvement was observed. CONCLUSIONS: From the biochemical point of view, treating encephalopathy due to VPA with carglumic acid is a logical step, as it reverses the blockage of the urea cycle conditioned by VPA. The mechanism proposed as being the one by which brain toxicity and, therefore, encephalopathy are produced is the passage of ammonia in the form of glutamine to the inside of the cell, which then returns to ammonia and glutamate in the mitochondria and leads to oxidative stress. Carglumic acid must be considered an important part of the treatment in adult patients with hyperammonaemic encephalopathy due to VPA, although a randomised clinical trial needs to be conducted with the drug in order to test its efficacy.

TITLE: Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.Introduccion. El acido valproico (VPA) es un farmaco principalmente usado en la epilepsia. La encefalopatia hiperamoniemica por VPA es una complicacion grave e infrecuente. El mecanismo por el que el VPA influye en la elevacion del amonio es bloqueando el ciclo de la urea, inhibiendo la N-acetilglutamato sintasa y disminuyendo la acetil coenzima A. De forma general, el tratamiento que se ha empleado ha sido la suspension del VPA y la administracion de arginina, carnitina, antibioticos, glucosa y restriccion proteica. La experiencia con acido carbaglumico se limita a comunicaciones de casos aislados de pacientes pediatricos. Casos clinicos. Descripcion de dos casos de pacientes adultos con encefalopatia por VPA tratados, ademas de las medidas convencionales, con acido carbaglumico. Tras el tratamiento con el farmaco se aprecia una normalizacion de los niveles de amonio. En uno de los casos, al existir otra causa de encefalopatia, no se aprecio mejora clinica. Conclusiones. Desde el punto de vista bioquimico es logico tratar la encefalopatia por VPA con acido carbaglumico, ya que revierte el bloqueo del ciclo de la urea condicionado por el VPA. El mecanismo propuesto por el que se produce la toxicidad cerebral y, por tanto, la encefalopatia, es el paso de amonio en forma de glutamina al interior celular, que retorna a amonio y glutamato en la mitocondria y genera estres oxidativo. El acido carbaglumico ha de considerarse como parte importante del tratamiento en pacientes adultos con encefalopatia hiperamoniemica por VPA, aunque es necesario realizar un ensayo clinico aleatorizado con el farmaco para comprobar su eficacia.

[Distal radius fractures: Which classification is the right one?] / Fractures de l'extrémité distale du radius : quelle classification choisir ?

None of the classification systems for distal radius fractures is ideal. However a validated system to analyze these fractures is available that is based on the "metaphysis, epiphysis, ulna" (MEU) classification and the "patient, accident, fracture" (PAF) system. It makes it possible to understand the injury and select the best treatment.