Unusual Surge of Acute Hepatitis A Cases in 2016 and 2017 in Malaga, Southern Spain: Characterization and Relationship with Other Concurrent European Outbreaks

Supplementary Materials: The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/jcm12206613/s1We aimed to describe the Hepatitis A virus (HAV) cases that arose in Malaga (Spain) in 2016 and 2017 when the European Centre for Disease Prevention and Control (ECDC) reported several outbreaks among men who have sex with men (MSM). Therefore, we conducted a retrospective study gathering demographic, clinical, and immunological data from the acute HAV patients attending our hospital between March 2016 and December 2017. Additionally, VP1/P2A region was amplified from serum samples, sequenced, and genotyped. We finally performed a phylogenetic analysis, including the HAV strains from the other European outbreaks. A total of 184 HAV cases were reported, with the highest number in March 2017. The cohort mostly comprised Spaniards (81.0%), males (84.8%), and MSM (72.3%), with a median age of 33.0 years (interquartile range (IQR) = 25.0–43.0). Most patients exhibited symptoms. In addition, a successful amplification and sequencing of the VP1/P2A region was performed in 25 out of 106 serum samples (23.6%). All the sequences belonged to the genotype IA, and 20 were phylogenetically related to VRD_521_2016, first described in the United Kingdom (UK). In conclusion, HAV cases emerged in Malaga in 2016 and 2017, showing an epidemic character phylogenetically related to the predominant strain first detected in the UK. Characteristics of the cohort were similar to those from the European outbreaks.Unicaja Foundatio

Ultrasound imaging assessment of the diaphragm and abdominal muscles in people with a recent history of moderate Covid-19 infection and healthy participants:A cross-sectional pilot study

[Abstract] Coronavirus disease (Covid-19) is a highly infectious disease caused by the SARS-CoV-2 virus and is associated with a decrease of respiratory, physical, and sychological function, subsequently affecting quality of life. The aim of the present pilot study was to use ultrasound imaging (USI) to evaluate and compare the thickness of the diaphragm and abdominal muscles between individuals recently diagnosed with moderate Covid-19 infection and healthy individuals. Methods: A cross-sectional observational pilot study was performed. A total sample of 24 participants were recruited from a private medical center (Madrid, Spain): Covid-19 (n = 12) and healthy controls (n = 12). The external oblique (EO), internal oblique (IO), transversus abdominis (TrA), rectus abdominis (RA), interrecti distance (IRD) and diaphragm thickness were assessed using USI during inspiration, expiration and during contraction. Results: USI measurements of the thickness of EO, IO, TrA, RA, IRD and the diaphragm did not differ significantly between groups during inspiration, expiration or during contraction (all P > 0.05). Conclusions: These preliminary results suggest that the morphology of the abdominal muscles and diaphragm is not altered in people with a recent history of moderate Covid-19 infection

Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes

Anèmia de Fanconi; Mozobil; Teràpia gènicaAnemia de Fanconi; Mozobil; Terapia génicaFanconi anemia; Mozobil; Gene therapyDifficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34+ cells/μL required to initiate apheresis. A median of 21.8 CD34+ cells/μL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34+ cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34+ cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34+ cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34+ cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.This work was supported by grants from the European Commission’s Seventh Framework Program (HEALTH-F5-2012-305421 to the EUROFANCOLEN Consortium, J.A.B., J. Sevilla, C.D.-d.-H., J. Soulier, and J. Surralles), Ministerio de Sanidad, Servicios Sociales e Igualdad (EC11/060 and EC11/550 to C.D.-d.-H., J. Sevilla, J.A.B., and J. Surralles), Ministerio de Economía, Comercio y Competitividad and Fondo Europeo de Desarrollo Regional (SAF2015-68073-R, RTI2018-097125-B-I00 to P.R. and RTI2018-098419-B-I00 to J. Surralles), Fondo de Investigaciones Sanitarias at the Instituto de Salud Carlos III (RD12/0019/0023 to J.C.S.), and Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (AvanCell Project; B2017/BMD3692). CIBERER is an initiative of the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional. J. Surralles is supported by ICREA Academia and FARF

Estudio experimental de la rotura capilar de chorros líquidos estirados por gravedad

La rotura de chorros líquidos en gotas ha atraído la atención de muchos científicos e ingenieros durante los últimos siglos. Se trata de un proceso en el que intervienen perturbaciones que crecen debido a una inestabilidad capilar mientras son advectadas por el flujo, hasta que se hacen lo suficientemente grandes como para provocar la rotura del chorro (Eggers, 2008). Este fenómeno se encuentra ampliamente en la vida cotidiana, ya sea en forma de un hilo de miel que cae por su propio peso o en un chorro de agua del grifo, así como en aplicaciones industriales. En este último ámbito, los chorros estirados son de interés debido a que permiten la producción de pequeñas gotas sin recurrir a inyectores de tamaño micrométrico que podrían obstruirse fácilmente. Se han desarrollado diferentes técnicas para su obtención, de las cuales el estiramiento gravitacional es la más simple y constituye el tema de este trabajo.Facultad de Ingenierí

Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children

Background: Osteoporosis incidence in children is increasing due to the increased survival rate of patients suffering from chronic diseases and the increased use of drugs that can damage bones. Recent changes made to the definition of childhood osteoporosis, along with the lack of guidelines or national consensuses regarding its diagnosis and treatment, have resulted in a wide variability in the approaches used to treat this disease. For these reasons, the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology has sounded the need for developing guidelines to standardize clinical practice with regard to this pathology. Methods: An expert panel comprised of 6 pediatricians and 5 rheumatologists carried out a qualitative literature review and provided recommendations based on evidence, when that was available, or on their own experience. The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system. A Delphi survey was conducted for those recommendations with an evidence level of IV or V. This survey was sent to all members of the SERPE. All recommendations that had a level of agreement higher or equal to 70% were included. Results: Fifty-one recommendations, categorized into eight sections, were obtained. Twenty-four of them presented an evidence level 4 or 5, and therefore a Delphi survey was conducted. This was submitted electronically and received a response rate of 40%. All recommendations submitted to the Delphi round obtained a level of agreement of 70% or higher and were therefore accepted. Conclusion: In summary, we present herein guidelines for the prevention, diagnosis and treatment of secondary childhood osteoporosis based on the available evidence and expert clinical experience. We believe it can serve as a useful tool that will contribute to the standardization of clinical practice for this pathology. Prophylactic measures, early diagnosis and a proper therapeutic approach are essential to improving bone health, not only in children and adolescents, but also in the adults they will become in the future

Consensus document on the progression and treatment response criteria in gastroenteropancreatic neuroendocrine tumors

Purpose Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of low incidence neoplasms characterized by a low proliferative activity and slow growth. Their response to targeted therapies is heterogeneous and often does not lead to tumor shrinkage. Thus, evaluation of the therapeutic response should difer from other kind of tumors. Methods To answer relevant questions about which techniques are best in the assessment of progression or treatment response a RAND/UCLA-based consensus process was implemented. Relevant clinical questions were listed followed by a systematic search of the literature. The expert panel answered all questions with recommendations, combining available evidence and expert opinion. Recommendations were validated through a questionnaire and a participatory meeting. Results Expert recommendations regarding imaging tools for tumor assessment and evaluation of progression were agreed upon. Available imaging techniques were reviewed and recommendations for best patient monitoring practice and the best way to evaluate treatment response were formulated

Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease

[EN] Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p. R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p. R190W mutation and another patient that harboured a MORC2 p. S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a new pathogenic mechanism to the long list of causes of Charcot-Marie-Tooth disease.This collaborative joint project is awarded by IRDiRC and funded by the Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (IR11/TREAT-CMT to T.S., S.I.P.P., F.P. and C.E.; PI12/00453 to C.E.; and PI12/0946 to T.S.), co-funded with FEDER funds. Additional support was provided by the Ramon Areces Foundation and by the ISCIII and the Centro de Investigacion Principe Felipe (CPII14/00002) to C.E.Sevilla, T.; Lupo, V.; Martínez-Rubio, D.; Sancho, P.; Sivera, R.; Chumillas, MJ.; García-Romero, M.... (2016). Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. Brain. 139:62-72. https://doi.org/10.1093/brain/awv311627213

Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations

[EN] Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified. We show that the full-length form of MORC2 is highly expressed in both embryonic and adult human neural tissues and that Morc2 expression is dynamically regulated in both the developing and the maturing murine nervous system. To determine the effect of the most common MORC2 mutations, p.S87L and p.R252W, we used several in vitro cell culture paradigms. Both mutations induced transcriptional changes in patient-derived fibroblasts and when expressed in rodent sensory neurons. These changes were more pronounced and accompanied by abnormal axonal morphology, in neurons expressing the MORC2 p.S87L mutation, which is associated with a more severe clinical phenotype. These data provide insight into the neuronal specificity of the mutated MORC2-mediated phenotype and highlight the importance of neuronal cell models to study the pathophysiology of CMT2Z.Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (PI15/00187 to C. E. and PI16/00403 to T. S.), co-funded with FEDER funds; Ramon Areces Foundation (CIVP17A2810 to C. E.); Generalitat Valenciana (PROMETEO/2018/135 to C. E. and T. S.); AFM-Telethon (21500 to C. E. and R. C.); National Health and Medical Research Council of Australia Grant (APP1046680 to M. K.); Czech Health Research Council (AZV16-30206A to P. L.); Swedish StratNeuro program grant; Swedish Research Council (2015-02394 to R. C.). C. E. had a 'Miguel Servet' contract funded by the ISCIII and the Centro de Investigacion Principe Felipe (CPII14/00002). P. S. is the recipient of a FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Sancho, P.; Bartesaghi, L.; Miossec, O.; García-García, F.; Ramírez-Jiménez, L.; Siddell, A.; Ajkesson, E.... (2019). Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations. Human Molecular Genetics. 28(10):1629-1644. https://doi.org/10.1093/hmg/ddz00616291644281

Una exploración de la parentalidad en la Modernidad líquida

While chemical contraception made “sex without reproduction” possible, new reproductive technologies facilitate “reproduction without sex”, which at the same time enables a formidable range of apparently naturalized family configurations, in liquid modernity. We are currently assisting in the construction of links, roles and functions that move away from those traditional paradigms, which until the end of the 20th century seemed immutable. In this research, the aim is to contribute –from a psychoanalytic perspective- to the exploration of those representations of parenting that take place in the context of liquid Modernity, based on the supply –and demand- of medically assisted reproduction. In reference to the research that is currently carried out from the Graduate School of the UNLaM (CyTMA2 2020 Call “New representations of parenting. From assisted reproduction in liquid modernity”), we present below, as the first progress report, its theoretical framework.Mientras la anticoncepción química hizo posible el “sexo sin reproducción”, las nuevas tecnologías reproductivas facilitan la “reproducción sin sexo”, lo que a la vez da lugar, en la Modernidad líquida, a un formidable abanico de configuraciones familiares, aparentemente naturalizadas. Asistimos en la actualidad a la construcción de vínculos, roles y funciones que se alejan de aquellos paradigmas tradicionales, que hasta fines del siglo XX parecían inmutables. En esta pesquisa aspiramos a contribuir –desde una perspectiva psicoanalítica- a la exploración de aquellas representaciones de la parentalidad que tienen lugar en el contexto de la Modernidad líquida, a partir de la oferta –y la demanda- de reproducción médicamente asistida. Presentamos a continuación, en referencia a esta investigación que actualmente se lleva a cabo desde la Escuela de Posgrado de la UNLaM (Convocatoria CyTMA2 2020 “Nuevas representaciones de la parentalidad. A partir de la reproducción asistida en la Modernidad líquida”), un primer informe de avances, que comprende el marco teórico de la misma