Development of Bioactive Hybrid Poly(lactic acid)/Poly(methyl methacrylate) (PLA/PMMA) Electrospun Fibers Functionalized with Bioglass Nanoparticles for Bone Tissue Engineering Applications.

Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.

BACKGROUND: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. METHODS: We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). RESULTS: ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. CONCLUSIONS: ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.

Uncertainty and associated risks in the analysis of pesticides in homogeneous paprika samples.

In this study, risk estimation based on sampling and subsampling uncertainty was performed for pesticide analysis in homogeneous spice products such as paprika. The results of the subsampling were also used to estimate the minimum weight necessary in subsampling to minimize overall uncertainty. The results show that subsampling has more uncertainty than sampling in the product due to high homogeneity in the manufacturer's batch. On the other hand, results using the Monte Carlo (MC) simulation on the size of the subsample indicate that uncertainty is lower for weights between 20 and 30 g and increases for sample sizes of 100 g. A sample size of 30 g was used for saffron, and the values simulated with the MC method were confirmed.

[Factors associated with the duration of SARS-CoV-2 infection in healthcare professionals at a second-level public hospital in the Community of Madrid (Spain) during the sixth wave.] / Factores asociados a la duración de la infección por SARS-CoV-2 en profesionales sanitarios de un hospital público de segundo nivel de la Comunidad de Madrid durante la sexta ola.

OBJECTIVE: The incidence of COVID-19 infections among health professionals during the sixth wave has suffered an exponential increase, mainly due to the rapid community transmission caused by the Omicron variant. The main objective of the study was to evaluate the time to negativization in COVID-positive health professionals during the sixth wave, according to the PDIA result; and secondarily, to evaluate the possible influence of other factors (previous infection, vaccination, sex, age, job position) on the time to get negative status. METHODS: A descriptive, longitudinal, observational and retrospective study was carried out at Infanta Sofía University Hospital (Madrid, Spain). Made from the registry of the Occupational Risk Prevention Service of suspected or confirmed cases of SARS-COV-2 infection in health professionals, during the period between November 1, 2021 and February 28, 2022. Bivariate comparisons were made using Mann Whitney, Kruskal Wallis or Chi-square test (or exact test) according to variables. Subsequently, logistic regression (explanatory model) was performed. RESULTS: The cumulative incidence of SARS-COV-2 infection in health professionals was 23.07%. The mean time to become negative was 9.94 days. Only the history of previous SARS-COV-2 infection had a statistically significant influence on the time to negativization of PDIA. The variables vaccination, sex and age had no effect on the time to negativization of PDIA. CONCLUSIONS: Professionals with a history of COVID-19 infection present lower times of negativization than those who had not have the disease. The results of our study confirm the immune escape of the vaccine against COVID-19, since more than 95% of those infected had received a complete vaccination schedule.

OBJETIVO: La incidencia de contagios por COVID-19 entre profesionales sanitarios durante la sexta ola, ha sufrido un incremento exponencial motivado principalmente por la rápida trasmisión comunitaria ocasionada por la variante Ómicron. El objetivo principal del estudio fue evaluar el tiempo de negativización en los profesionales sanitarios COVID positivos durante la sexta ola, según resultado de PDIA; y, de forma secundaria, evaluar la posible influencia de otros factores (infección previa, vacunación, sexo, edad, puesto de trabajo) en el tiempo de negativización. METODOS: Se realizó un estudio descriptivo, longitudinal, observacional y retrospectivo en el Hospital Universitario Infanta Sofía (Madrid), a partir del registro del Servicio de Prevención de Riesgos Laborales de casos sospechosos o confirmados de infección por SARS-COV-2 en profesionales sanitarios, durante el periodo comprendido entre el 1 de noviembre de 2021 y el 28 de febrero de 2022. Se hicieron comparaciones bivariadas mediante Mann Whitney, Kruskal Wallis o test de Chi-cuadrado (o test exacto) según variables. Posteriormente se realizó regresión logística (modelo explicativo). RESULTADOS: La incidencia acumulada de infección por SARS-COV-2 en profesionales sanitarios fue del 23,07%. El tiempo medio en negativizar fue de 9,94 días. Únicamente el antecedente de infección previa por SARS-COV-2 influyó de forma estadísticamente significativa en el tiempo de negativización de PDIA. Las variables vacunación, sexo y edad no tuvieron efecto en el tiempo de negativización de PDIA. CONCLUSIONES: Los profesionales con antecedente de infección por COVID-19 presentan tiempos inferiores de negativización que aquellos que no han pasado la enfermedad. Los resultados de nuestro estudio constatan el escape inmunológico de la vacuna frente al COVID-19, pues más del 95% de los infectados habían recibido una pauta de vacunación completa.

Trends in dithiocarbamates food research: A bibliometric vision.

Dithiocarbamate Fungicides (DTFs) are widely analyzed and studied mainly due to the fact that they play an important role in the cultivation of fruits and vegetables. This manuscript aims to display the results of a bibliometric analysis based on the Web of Science© database, performed in the DTF and food research area. A total of 374 publications were examined. The most scientific production was concentrated between 2012 and 2021, showing a decrease of 32% over the last two years. The Journal of Agricultural and Food Chemistry, India, and Sardar Vallabhbhai National Institute of Technology were the most productive journal, country, and institution, respectively. Reference Publication Year Spectroscopy index showed a decrease of 95% in the last last years studied. Finally, current and future trends should focus on keywords such as individual DTF (Mancozeb, Thiram and Maneb), metabolites (Ethylenethiourea, Propilenthiourea) and a change in the analysis methodology: HPLC versus traditional GC.

Is the prognosis of non-hypertensive, COVID-19 patients treated with renin-angiotensin-aldosterone system inhibitors more uncertain?

Previous studies suggested that ongoing treatment with renin-angiotensin-aldosterone system (RAAS) inhibitor drugs may alter the course of SARS-CoV-2 infection and promote the development of more severe forms of the disease. The authors conducted a comparative, observational study to retrospectively analyze data collected from 394 patients admitted to ICU due to SARS-CoV-2 pneumonia. The primary aim of the study was to establish an association between the use of RAAS inhibitor drugs and mortality in the ICU. The secondary aims of the study were to establish an association between the use of RAAS inhibitor drugs and clinical severity at ICU admission, the need for tracheal intubation, total days of mechanical ventilation, and the ICU length of stay. The authors found no statistically significant difference in ICU mortality between patients on RAAS inhibitor drugs at admission and those who were not (31.3% versus 26.2% mortality, p-value 0.3). However, the group of patients taking RAAS inhibitor drugs appeared to be more critical at ICU admission, and this difference became statistically significant in the subgroup of non-hypertensive patients. ICU mortality in the subgroup of non-hypertensive patients treated with RAAS inhibitor drugs also tended to be higher. Overexpression of the angiotensin-converting enzyme 2 (ACE2) in human cells, induced by RAAS inhibitor drugs, promotes viral entry-replication of SARS-CoV-2 and alters the basal balance of the RAAS, which may explain the findings observed in the present study. These phenomena may be amplified in non-hypertensive patients treated with RAAS inhibitor therapy.

Postoperative Intracranial Hypotension-Associated Venous Congestion after Spinal Surgery Managed with Multiple Blood Patches: Case Report.

BACKGROUND: Postoperative intracranial hypotension-associated venous congestion (PIHV) is a rare event. The authors report the case of a patient presenting with PIHV after spinal surgery following the sudden loss of cerebrospinal fluid (CSF) induced by suction drainage. METHODS: A 69-year-old patient underwent uneventful revision surgery for wound dehiscence after lumbar surgery with placement of a subfascial suction drain. RESULTS: Postoperatively, the patient presented with fluctuating consciousness and a generalized tonic-clonic seizure. Computed tomography (CT) and serial magnetic resonance imaging (MRI) were performed showing convexity subarachnoid hemorrhages (SAHs), diffuse swelling of the brain and thalami and striatum bilaterally without diffusion restriction, and signs of intracranial hypertension resulting in pseudohypoxic brain swelling in PIHV. A dural leak at L3-L4 was treated with several CT-guided patches combining autologous blood and fibrin glue injections. The patient recovered without neurologic deficit and follow-up MRI revealed progressive complete reversal of brain swelling, and re-expansion of CSF spaces. CONCLUSION: PIHV is a rare but potentially fatal entity. Awareness of PIHV after cranial or spinal surgery leads to early treatment of CSF hypovolemia and possibly better clinical outcome. Following acute CSF volume loss, an acute elevation of cerebral blood volume overcoming autoregulatory mechanisms seems a likely explanation for diffuse cerebral vasogenic edema and SAH in PIHV.

Concordance in Adolescent and Caregiver Report of Social Determinants of Health.

INTRODUCTION: Screening youth for negative social determinants of health is a widespread practice across healthcare settings in the U.S., with such systems almost exclusively relying on caregiver reports. Little work has sought to identify the social determinants of health adolescents identify as having the largest influence on their health and well-being or the extent to which adolescents agree with their caregiver. This study sought to (1) identify the most prevalent and influential negative social determinants of health, according to adolescent reports, and (2) assess concordance between adolescent and caregiver reports of social determinants of health. METHODS: In Fall 2021, the study team conducted a cross-sectional, observational study within a predominately Latinx urban high school. The team invited all students and their caregivers to participate, resulting in 520 adolescent and 66 caregiver respondents (73% and 9% response rates, respectively). Data analyses occurred in 2022. RESULTS: The most frequent adolescent-reported negative social determinants of health was stress (67%), followed by financial hardship (27%). The negative social determinant of health with the highest ranking of preventing adolescents from living their best and healthiest lives was depression, followed by isolation and stress. Concordance between caregiver and adolescent report of negative social determinants of health was very low across all negative social determinants of health (Krippendorf's α= -0.08 to 0.21). Caregivers under-reported adolescents' social and mental health needs, whereas adolescents under-reported material needs. CONCLUSIONS: A hybrid informant approach may be a best practice for social determinants of health screening among adolescents, whereby caregivers and adolescents report material needs, and adolescents report social and mental health needs. Future work should evaluate the concordance between adolescent and caregiver social determinants of health reports in other settings.

Process-oriented metrics to provide feedback and assess the performance of students who are learning surgical procedures: The percutaneous dilatational tracheostomy case.

PURPOSE: Assessing competency in surgical procedures is key for instructors to distinguish whether a resident is qualified to perform them on patients. Currently, assessment techniques do not always focus on providing feedback about the order in which the activities need to be performed. In this research, using a Process Mining approach, process-oriented metrics are proposed to assess the training of residents in a Percutaneous Dilatational Tracheostomy (PDT) simulator, identifying the critical points in the execution of the surgical process. MATERIALS AND METHODS: A reference process model of the procedure was defined, and video recordings of student training sessions in the PDT simulator were collected and tagged to generate event logs. Three process-oriented metrics were proposed to assess the performance of the residents in training. RESULTS: Although the students were proficient in classic metrics, they did not reach the optimum in process-oriented metrics. Only in 25% of the stages the optimum was achieved in the last session. In these stages, the four more challenging activities were also identified, which account for 32% of the process-oriented metrics errors. CONCLUSIONS: Process-oriented metrics offer a new perspective on surgical procedures performance, providing a more granular perspective, which enables a more specific and actionable feedback for both students and instructors.

When Enterococcus faecalis becomes a murderer.

We describe the case of a 64 years old patient, known for an Enterococcus faecalis endocarditis on a 25 mm Edwards-Carpentier biological aortic valve in 2020, who was re-hospitalized one year later in cardiac surgery for a recurrence of Enterococcus faecalisbacteriemia. During hospitalization, the patient presented a cardiac arrest. The coronarography revealed an acute occlusion of the left coronary artery. The autopsy confirmed an Enterococcus faecalis thrombus on aortic valve and left coronary artery. Although systemic embolism is a common complication of infective endocarditis, septic embolism is an unsual cause of acute coronary syndrome and a very rare cause of cardiac arrest. Our case highlights a rare and potentially fatal complication of infective endocarditis: acute coronary syndrome on septic coronary embolism.

Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.

BACKGROUND AND OBJECTIVES: Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes. METHODS: A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm based on the network expansion of a seed group of GWMD-related genes derived from the Human Phenotype Ontology terms of each patient. RESULTS: We evaluated 126 patients (101 children and 25 adults) with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis, and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A, and PLP1, and a dual diagnosis underlying complex phenotypes in 6 families, underscoring the importance of genomic analysis to solve these cases. We discovered 9 candidate genes causing novel diseases and propose additional putative novel candidate genes for yet-to-be discovered GWMD. DISCUSSION: Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance.

Parallel shape divergence between ecotypes of the limpet Nacella concinna along the Antarctic Peninsula: a new model species for parallel evolution?

Parallel phenotypic divergence is the independent differentiation between phenotypes of the same lineage or species occupying ecologically similar environments in different populations. We tested in the Antarctic limpet Nacella concinna the extent of parallel morphological divergence in littoral and sublittoral ecotypes throughout its distribution range. These ecotypes differ in morphological, behavioural and physiological characteristics. We studied the lateral and dorsal outlines of shells and the genetic variation of the mitochondrial gene Cytochrome Oxidase subunit I from both ecotypes in 17 sample sites along more than 2,000 km. The genetic data indicate that both ecotypes belong to a single evolutionary lineage. The magnitude and direction of phenotypic variation differ between ecotypes across sample sites; completely parallel ecotype-pairs (i.e., they diverge in the same magnitude and in the same direction) were detected in 84.85% of lateral and 65.15% in dorsal view comparisons. Besides, specific traits (relative shell height, position of shell apex, and elliptical/pear-shape outline variation) showed high parallelism. We observed weak morphological covariation between the two shape shell views, indicating that distinct evolutionary forces and environmental pressures could be acting on this limpet shell shape. Our results demonstrate there is a strong parallel morphological divergence pattern in N. concinna along its distribution, making this Antarctic species a suitable model for the study of different evolutionary forces shaping the shell evolution of this limpet.

[Cardiac tamponade and myocarditis in a patient with acute SARS-CoV-2 infection]. / Taponamiento cardíaco y miocarditis en paciente con infección aguda por SARS-CoV-2.

We describe a patient with COVID-19, with pericardial effusion, cardiac tamponade and severe myocardial depression. A 51-year-old woman, previously healthy, with mild COVID-19 presented with three episodes of syncope. She was admitted to the emergency room. An electrocardiogram showed sinus rhythm, diffuse superior concavity ST 2 mv; a CT scan showed pericardial effusion, without lung pathological findings. Due to shock, dyspnoea and encephalopathy, the patient was admitted to intensive care, where she received vasopressor support and mechanical ventilation. A bedside ultrasound showed pericardial effusion and tamponade; drainage was performed; transoesophageal ultrasound showed moderate deterioration of biventricular systolic function; global longitudinal strain -14.2%, estimated Fey 43%; global circumferential strain -10.1%. Seven days after admission, CT scan revealed bilateral infiltrates and pericardial thickening with post-contrast enhancement and mild pericardial effusion. On day 12 post admission, inotropic support was discontinued; patient on mechanical ventilation weaning and haemodynamically stable.

Describimos una paciente con COVID-19, con derrame pericárdico, taponamiento cardíaco y depresión miocárdica grave. Mujer de 51 años, sin enfermedad previa, COVID-19 leve que presentó tres episodios de síncope en domicilio. El electrocardiograma mostró ritmo sinusal, ST de concavidad superior difuso 2 mv; en la tomografía se observó derrame pericárdico y parénquima pulmonar normal. Ingresó a terapia intensiva con shock y requerimiento de asistencia ventilatoria mecánica (AVM). En el ecocardiograma se observó derrame pericárdico y taponamiento; se realizó drenaje. El ecocardiograma transesofágico mostró deterioro moderado de función sistólica biventricular; strain longitudinal global ­14.2%, Fey estimada: 43%; deformación global circunferencial: ­10.1%. A los 7 días del ingreso, la tomografía reveló infiltrados bilaterales y engrosamiento pericárdico con realce post-contraste y derrame pericárdico leve. El día 12 posterior al ingreso, se suspendió el soporte inotrópico; y la paciente, hemodinámicamente estable, se desvinculó de la AVM.

Taponamiento cardíaco y miocarditis en paciente con infección aguda por SARS-CoV-2 / Cardiac tamponade and myocarditis in a patient with acute SARS-CoV-2 infection

Resumen Describimos una paciente con COVID-19, con derrame pericárdico, taponamiento cardíaco y depresión miocárdica grave. Mujer de 51 años, sin enfermedad previa, COVID-19 leve que presentó tres episodios de síncope en domicilio. El electrocardiograma mostró ritmo sinusal, ST de concavidad superior difuso 2 mv; en la tomografía se observó derrame pericárdico y parénquima pulmonar normal. Ingresó a terapia intensiva con shock y requerimiento de asistencia ventilatoria mecánica (AVM). En el ecocardiograma se obser vó derrame pericárdico y taponamiento; se realizó drenaje. El ecocardiograma transesofágico mostró deterioro moderado de función sistólica biventricular; strain longitudinal global -14.2%, Fey estimada: 43%; deformación global circunferencial: -10.1%. A los 7 días del ingreso, la tomografía reveló infiltrados bilaterales y engrosamiento pericárdico con realce post-contraste y derrame pericárdico leve. El día 12 posterior al ingreso, se suspendió el soporte inotrópico; y la paciente, hemodinámicamente estable, se desvinculó de la AVM.

Abstract We describe a patient with COVID-19, with pericardial effusion, cardiac tamponade and severe myocar dial depression. A 51-year-old woman, previously healthy, with mild COVID-19 presented with three episodes of syncope. She was admitted to the emergency room. An electrocardiogram showed sinus rhythm, diffuse superior concavity ST 2 mv; a CT scan showed pericardial effusion, without lung pathological findings. Due to shock, dyspnoea and encephalopathy, the patient was admitted to intensive care, where she received vasopressor support and mechanical ventilation. A bedside ultrasound showed pericardial effusion and tamponade; drainage was performed; transoesophageal ultrasound showed moderate deterioration of biventricular systolic function; global longitudinal strain -14.2%, estimated Fey 43%; global circumferential strain -10.1%. Seven days after admission, CT scan revealed bilateral infiltrates and pericardial thickening with post-contrast enhancement and mild pericardial effusion. On day 12 post admission, inotropic support was discontinued; patient on mechanical ventilation weaning and haemodynamically stable.

Hydrogen production automatic control in continuous microbial electrolysis cells reactors used in wastewater treatment.

In this paper, two control laws are proposed and applied in a model for a continuous Microbial Electrochemical Cells system. The used model is based on mass balances describing the behavior of substrate consumption, microbial growth, competition between anodophilic and methanogenic microorganisms for the carbon source in the anode, hydrogen generation, and electrical current production. The main control objective is to improve the electrical current generated and thus the production of bio-hydrogen gas in the reactor, using the dilution rate and the applied potential as individual control input variables. The control laws implemented are nonlinear adaptive type. In order to demonstrate its usefulness, numerical simulation runs involving multiple set-point changes and input perturbations were conducted for each control variable. The results of these simulations show that both control laws were able to respond adequately and efficiently to the disturbances and reach the reference value to which they were subjected. Moreover, it is possible to control both the electrical current produced and the hydrogen produced. Finally, these simulations also show that the highest rate of hydrogen production can be obtained using the applied potential as a control input, but such productivity is only attainable for a short period of time.

A novel hypomorphic splice variant in EIF2B5 gene is associated with mild ovarioleukodystrophy.

OBJECTIVE: To identify the genetic cause in an adult ovarioleukodystrophy patient resistant to diagnosis. METHODS: We applied whole-exome sequencing (WES) to a vanishing white matter disease patient associated with premature ovarian failure at 26 years of age. We functionally tested an intronic variant by RT-PCR on patient's peripheral blood mononuclear cells (PBMC) and by minigene splicing assay. RESULTS: WES analysis identified two novel variants in the EIF2B5 gene: c.725A > G (p.Tyr242Cys) and an intronic noncanonical mutation (c.1156 + 13G>A). This intronic mutation resulted into generation of various isoforms both in patient's PBMC and in the minigene splicing assay, showing that ~20% residual wild-type isoform is still expressed by the intronic-mutated allele alone, concordant with an hypomorphic effect of this variant. CONCLUSION: We report two novel variants in EIF2B5, one of them a noncanonical intronic splice variant, located at a +13 intronic position. This position is mutated only in 0.05% of ClinVar intronic mutations described so far. Furthermore, we illustrate how minigene splicing assay may be advantageous when validating splice-altering variants, in this case highlighting the coexistence of wild-type and mutated forms, probably explaining this patient's milder, late-onset phenotype.

SARS-CoV-2 and rhinovirus/enterovirus co-infection in a critically ill young adult patient in Colombia / [Coinfección por SARS-CoV-2 y rinovirus-enterovirus en una paciente adulta joven críticamente enferma en Colombia].

The current SARS-CoV-2 pandemic has caused a huge global public health problem. We report the case of a young adult patient with laboratory-confirmed SARS-CoV-2. We describe the identification of the virus and the clinical course, diagnosis, and treatment of the infection including her rapid clinical deterioration from the mild initial symptoms, which progressed to multilobar pneumonia requiring admission to the intensive care unit. This case highlights the importance of establishing a diagnosis based on the clinical findings and the patient's history bearing in mind the possibility of gastrointestinal symptoms in addition to respiratory ones. Besides, the presence of risk factors should be investigated; in this case, we proposed obesity as a possible risk factor. Furthermore, limitations in diagnostic tests and the possibility of co-infection with other respiratory pathogens are highlighted. We describe the imaging, laboratory findings, and treatment taking into account the limited current evidence.

La actual pandemia por SARS-CoV-2 ha ocasionado un enorme problema de salud pública mundial. Se reporta el caso de una paciente adulta joven con SARS-CoV-2 confirmado por laboratorio. Se describe la identificación del virus y el curso clínico, el diagnóstico y el tratamiento de la infección. La paciente tuvo un rápido deterioro clínico a partir de síntomas iniciales leves que progresaron a una neumonía multilobar que requirió su hospitalización en la unidad de cuidados intensivos. Se destaca la importancia de establecer un diagnóstico basado en la clínica y los antecedentes del paciente, y considerando los posibles síntomas gastrointestinales además de los respiratorios. Asimismo, debe indagarse sobre la presencia de factores de riesgo, en este caso, la obesidad. También se señalan las limitaciones en las pruebas diagnósticas y la posibilidad de infección concomitante con otros agentes patógenos respiratorios, así como los hallazgos en las imágenes diagnósticas, los exámenes de laboratorio y el tratamiento en el marco de la limitada información con que se cuenta actualmente.

Coinfección por SARS-CoV-2 y rinovirus-enterovirus en una paciente adulta joven críticamente enferma en Colombia / SARS-CoV-2 and rhinovirus/enterovirus co-infection in a critically ill young adult patient in Colombia

La actual pandemia por SARS-CoV-2 ha ocasionado un enorme problema de salud pública mundial. Se reporta el caso de una paciente adulta joven con SARS-CoV-2 confirmado por laboratorio. Se describe la identificación del virus y el curso clínico, el diagnóstico y el tratamiento de la infección. La paciente tuvo un rápido deterioro clínico a partir de síntomas iniciales leves que progresaron a una neumonía multilobar que requirió su hospitalización en la unidad de cuidados intensivos. Se destaca la importancia de establecer un diagnóstico basado en la clínica y los antecedentes del paciente, y considerando los posibles síntomas gastrointestinales además de los respiratorios. Asimismo, debe indagarse sobre la presencia de factores de riesgo, en este caso, la obesidad. También se señalan las limitaciones en las pruebas diagnósticas y la posibilidad de infección concomitante con otros agentes patógenos respiratorios, así como los hallazgos en las imágenes diagnósticas, los exámenes de laboratorio y el tratamiento en el marco de la limitada información con que se cuenta actualmente.

The current SARS-CoV-2 pandemic has caused a huge global public health problem. We report the case of a young adult patient with laboratory-confirmed SARS-CoV-2. We describe the identification of the virus and the clinical course, diagnosis, and treatment of the infection including her rapid clinical deterioration from the mild initial symptoms, which progressed to multilobar pneumonia requiring admission to the intensive care unit. This case highlights the importance of establishing a diagnosis based on the clinical findings and the patient's history bearing in mind the possibility of gastrointestinal symptoms in addition to respiratory ones. Besides, the presence of risk factors should be investigated; in this case, we proposed obesity as a possible risk factor. Furthermore, limitations in diagnostic tests and the possibility of co-infection with other respiratory pathogens are highlighted. We describe the imaging, laboratory findings, and treatment taking into account the limited current evidence.