Effects of expeller soybean on growth performance, amino acid digestibility and intestinal integrity.

Expeller soybean (ESB) is a widely used protein source in broiler diets due to its high amino acid digestibility. However, improper heat processing of ESB can negatively affect nutrient digestion, absorption, and metabolism leading to decreased growth performance. The study aimed to investigate the impact of varying processing temperatures on growth performance, amino acid digestibility (AID), and intestinal integrity using 3 different commercial batches of ESB processed at distinct temperatures. These temperatures were 182°C (normal-control), 199°C (overcooked), and 154°C (undercooked). 1,860 off-sex male Cobb 500 broilers were allocated randomly to these treatments, with 10 replicate floor pens (62 birds/pen) from 1 to 35 d of age. Birds consuming the overcooked ESB exhibited significantly lower body weight gain (BWG) and feed intake (FI) on d 14, 28, and 35. They also showed higher feed conversion ratio (FCR) and smaller relative right pectoralis major (RPM) weights at d 35. Meanwhile, birds fed undercooked ESB demonstrated reduced BWG at d 14. Serum fluorescein isothiocyanate-dextran (FITC-d; 4 kD) concentrations on d 16 were notably elevated in birds fed overcooked ESB, indicating increased gut permeability. Overcooked ESB reduced the AID coefficients of several amino acids on d 14 and 28, with Lys experiencing the highest reduction (8%). Undercooked ESB, however, mainly affected the AID of Val, and Phe at d 28. In conclusion, overcooked ESB decreased amino acid digestibility, impaired gut barrier function, and led to diminished growth performance. Conversely, undercooked ESB primarily affected the digestibility of Val and Phe and resulted in reduced BWG at d 14. These findings underscore the critical role of proper heat processing in preserving the nutritional quality of ESB in broiler diets, influencing optimal growth performance, and maintaining intestinal health.

Intervenciones psicoeducativas sobre salud mental con adolescentes en contextos escolares: una revisión sistemática / Psychoeducational interventions on mental health with adolescents in scholar contexts: a systematic review

La adolescencia es una etapa de transición en la que pueden aparecer dificultades a nivel personal, académico, familiar y social. Se estima que el 20% de adolescentes se enfrentará a algún problema de salud mental. El objetivo de este trabajo es realizar una revisión sistemática sobre intervenciones psicoeducativas para la prevención y/o la promoción de la salud mental en adolescentes dentro del contexto escolar. Para ello, se ha realizado una búsqueda en las bases de datos Web of Science, Scopus y PsycInfo, en la que se han identificado inicialmente 105 artículos, y se han seleccionado 11 estudios sobre programas psicoeducativos que reunían los criterios de inclusión. Tras esta revisión, se puede afirmar que la mayoría de intervenciones psicoeducativas analizadas son efectivas en la promoción del conocimiento de salud mental, la reducción del estigma y la adquisición de estrategias y habilidades con adolescentes. (AU)

Adolescence is a critical life phase during which people are faced with important decisions at the personal, academic, familial, and social level, what often comes with many difficulties. It is estimated that around 20% of adolescents will experience mental health difficulties. This study reviews psychoeducational interventions aimed at the prevention and promotion of adolescents’ mental health within the school context. A systematic search was conducted in Web of Science, Scopus and PsycInfo, through which 105 articles were identified and 11 were selected according to the inclusion criteria. After reviewing the main aspects of each program, it can be concluded that, overall, psychoeducational interventions are effective. These interventions promote mental health knowledge, reduce associated stigmas, and provide useful strategies for navigating problems. (AU)

Microelectrode Arrays Measure Blocking of Voltage-Gated Calcium Ion Channels on Supported Lipid Bilayers Derived from Primary Neurons.

Drug studies targeting neuronal ion channels are crucial to understand neuronal function and develop therapies for neurological diseases. The traditional method to study neuronal ion-channel activities heavily relies on the whole-cell patch clamp as the industry standard. However, this technique is both technically challenging and labour-intensive, while involving the complexity of keeping cells alive with low throughput. Therefore, the shortcomings are limiting the efficiency of ion-channel-related neuroscience research and drug testing. Here, this work reports a new system of integrating neuron membranes with organic microelectrode arrays (OMEAs) for ion-channel-related drug studies. This work demonstrates that the supported lipid bilayers (SLBs) derived from both neuron-like (neuroblastoma) cells and primary neurons are integrated with OMEAs for the first time. The increased expression of voltage-gated calcium (CaV) ion channels on differentiated SH-SY5Y SLBs  compared to non-differentiated ones is sensed electrically. Also, dose-response of the CaV ion-channel blocking effect on primary cortical neuronal SLBs from rats is monitored. The dose range causing ion channel blocking is comparable to literature. This system overcomes the major challenges from traditional methods (e.g., patch clamp) and showcases an easy-to-test, rapid, ultra-sensitive, cell-free, and high-throughput platform to monitor dose-dependent ion-channel blocking effects on native neuronal membranes.

Near-term pregnant women in the Dominican Republic experience high rates of Group B Streptococcus rectovaginal colonization with virulent strains.

Maternal colonization with Group B Streptococcus (GBS) is an important cause of stillbirth, prematurity, and serious infection and death in infants worldwide. Resource constraints limit prevention strategies in many regions. Maternal GBS vaccines in development could be a more accessible prevention strategy, but data on geographic variations in GBS clones are needed to guide development of a broadly effective vaccine. In the Dominican Republic (DR), limited data suggest that pregnant women experience GBS colonization at rates among the highest globally. We aimed to determine the prevalence of maternal rectovaginal GBS colonization and describe clonal characteristics of colonizing strains in the DR. A cross-sectional study assessed rectovaginal GBS colonization in 350 near-term pregnant women presenting for routine prenatal care at an urban tertiary center in the DR. Rectovaginal samples were tested with chromogenic Strep B Carrot Broth and cultured for confirmatory whole-genome sequencing. In a secondary analysis, participants' demographics and histories were assessed for association with GBS colonization. Rectovaginal GBS colonization occurred in 26.6% of women. Serotypes Ia, Ib, II, III, IV, and V were detected, with no one serotype predominating; serotype III was identified most frequently (21.5%). Virulent and emerging strains were common, including CC17 (15.1%) and ST1010 (17.2%). In this first characterization of maternal GBS serotypes in the DR, we found high rates of rectovaginal colonization including with virulent and emerging GBS strains. The serotypes observed here are all targeted by candidate hexavalent GBS vaccines, suggesting effective protection in the DR.

A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.

During aging, proteostasis capacity declines and distinct proteins become unstable and can accumulate as protein aggregates inside and outside of cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of cytoplasmic protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of 3 core protein quality control systems, namely chaperones, the proteasome, and macroautophagy, leads to lower levels of age-dependent protein aggregation in Caenorhabditis elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism that selectively targets newly synthesized proteins to suppress their aggregation and associated proteotoxicity. The safety mechanism relies on macroautophagy-independent lysosomal degradation and involves several previously uncharacterized components of the intracellular pathogen response (IPR). We propose that this protective mechanism engages an anti-aggregation machinery targeting aggregating proteins for lysosomal degradation.

Diversity of dynamic voltage patterns in neuronal dendrites revealed by nanopipette electrophysiology.

Dendrites and dendritic spines are the essential cellular compartments in neuronal communication, conveying information through transient voltage signals. Our understanding of these compartmentalized voltage dynamics in fine, distal neuronal dendrites remains poor due to the difficulties inherent to accessing and stably recording from such small, nanoscale cellular compartments for a sustained time. To overcome these challenges, we use nanopipettes that permit long and stable recordings directly from fine neuronal dendrites. We reveal a diversity of voltage dynamics present locally in dendrites, such as spontaneous voltage transients, bursting events and oscillating periods of silence and firing activity, all of which we characterized using segmentation analysis. Remarkably, we find that neuronal dendrites can display spontaneous hyperpolarisation events, and sustain transient hyperpolarised states. The voltage patterns were activity-dependent, with a stronger dependency on synaptic activity than on action potentials. Long-time recordings of fine dendritic protrusions show complex voltage dynamics that may represent a previously unexplored contribution to dendritic computations.

α-Synuclein fibril and synaptic vesicle interactions lead to vesicle destruction and increased lipid-associated fibril uptake into iPSC-derived neurons.

Monomeric alpha-synuclein (aSyn) is a well characterised protein that importantly binds to lipids. aSyn monomers assemble into amyloid fibrils which are localised to lipids and organelles in insoluble structures found in Parkinson's disease patient's brains. Previous work to address pathological aSyn-lipid interactions has focused on using synthetic lipid membranes, which lack the complexity of physiological lipid membranes. Here, we use physiological membranes in the form of synaptic vesicles (SV) isolated from rodent brain to demonstrate that lipid-associated aSyn fibrils are more easily taken up into iPSC-derived cortical i3Neurons. Lipid-associated aSyn fibril characterisation reveals that SV lipids are an integrated part of the fibrils and while their fibril morphology differs from aSyn fibrils alone, the core fibril structure remains the same, suggesting the lipids lead to the increase in fibril uptake. Furthermore, SV enhance the aggregation rate of aSyn, yet increasing the SV:aSyn ratio causes a reduction in aggregation propensity. We finally show that aSyn fibrils disintegrate SV, whereas aSyn monomers cause clustering of SV using small angle neutron scattering and high-resolution imaging. Disease burden on neurons may be impacted by an increased uptake of lipid-associated aSyn which could enhance stress and pathology, which in turn may have fatal consequences for neurons.

Controversies in neuroimmunology: multiple sclerosis, vaccination, SARS-CoV-2 and other dilemas / Controversias en neuroinmunología: esclerosis múltiple, vacunación, SARS-CoV-2 y otros dilemas

Neuroimmunology is a discipline that increasingly broadens its horizons in the understanding of neurological diseases. At the same time, and in front of the pathophysiological links of neurological diseases and immunology, specific diagnostic and therapeutic approaches have been proposed. Despite the important advances in this discipline, there are multiple dilemmas that concern and filter into clinical practice. This article presents 15 controversies and a discussion about them, which are built with the most up-to-date evidence available. The topics included in this review are: steroid decline in relapses of multiple sclerosis; therapeutic recommendations in MS in light of the SARS-CoV-2 pandemic; evidence of vaccination in multiple sclerosis and other demyelinating diseases; overview current situation of isolated clinical and radiological syndrome; therapeutic failure in multiple sclerosis, as well as criteria for suspension of disease-modifying therapies; evidence of the management of mild relapses in multiple sclerosis; recommendations for prophylaxis against Strongyloides stercolaris; usefulness of a second course of immunoglobulin in the Guillain-Barré syndrome; criteria to differentiate an acute-onset inflammatory demyelinating chronic polyneuropathy versus Guillain-Barré syndrome; and, the utility of angiotensin-converting enzyme in neurosarcoidosis. In each of the controversies, the general problem is presented, and specific recommendations are offered that can be adopted in daily clinical practice.

La neuroinmunología es una disciplina que cada vez amplía más sus horizontes en la comprensión de las enfermedades neurológicas. Contemporáneamente, y a la luz de los nexos fisiopatológicos de las enfermedades neurológicas y la inmunología, se han planteado enfoques diagnósticos y terapéuticos específicos. A pesar de los importantes avances de esta disciplina, existen múltiples dilemas que le conciernen y se filtran en la práctica clínica. En esta revisión, se presentan y discuten 15 controversias, las cuales se construyen con la información clínica disponible más actualizada. Los temas incluidos son: disminución de esteroides en recaídas de esclerosis múltiple; recomendaciones terapéuticas en esclerosis múltiple a la luz de la pandemia por el SARS-CoV-2; evidencia de vacunación en esclerosis múltiple y en otras enfermedades desmielinizantes; panorama actual del síndrome clínico y radiológico aislado; y fallas terapéuticas en esclerosis múltiple; además, criterios para suspender las terapias modificadoras de la enfermedad; evidencia del manejo en recaídas leves; recomendaciones para la profilaxis contra Strongyloides stercolaris; utilidad de un segundo ciclo de inmunoglobulina en el síndrome de Guillain-Barré; criterios para diferenciar una polineuropatía crónica desmielinizante inflamatoria de inicio agudo de un síndrome de Guillain-Barré y, utilidad de la enzima convertidora de angiotensina en neurosarcoidosis. En cada una de las controversias, se presenta la problemática general y se ofrecen recomendaciones específicas que pueden adoptarse en la práctica clínica diaria.

Necrotizing Hepatitis Associated with Clostridium perfringens in Broiler Chicks.

In this retrospective study we describe unusual cases of clostridial hepatitis associated with high mortality in young broiler chicks. Eleven cases of necrotizing hepatitis in broiler chicks from four companies were submitted to the Poultry Diagnostic and Research Center or the Georgia Poultry Laboratory Network between 2017 and 2020. In most flocks, increased 3-day mortality was followed by an elevated 7-day mortality. Gross lesions included green to dark brown discoloration of the liver, congested lungs, serosanguineous fluid in the caudoventral aspect of the abdomen, and emphysema in the yolk sacs. In birds older than a week of age, disease with neurologic signs became evident and consisted of tremors, stargazing, and incoordination. Histopathologic evaluation revealed multifocal to coalescing fibrinoheterophilic and necrotizing hepatitis associated with gram-positive, long, rod-shaped bacteria. Formalin-fixed liver samples from six cases out of eight cases tested were positive for Clostridium perfringens by immunohistochemistry. Liver samples from two cases were culture positive for Clostridium spp., and C. perfringens was isolated from one sample. Toxinotyping by PCR performed in seven samples revealed the presence of the genes that code for alpha toxin phospholipase C (cpa or plc) and necrotic enteritis toxin B-like (netB) in six samples and as well as C. perfringens large cytotoxin (tpeL) in one sample. Broiler breeders are the suspected source of the infection, and testing revealed C. perfringens in hatchery samples and among broiler breeder flocks. Antimicrobial therapy was coupled with enhanced sanitation at the farm and hatchery in that company, markedly decreasing the mortality and clinical signs. This is the first comprehensive evaluation of clostridial necrotizing hepatitis in newly hatched chicks, and the second ever reported in the literature.

Hepatitis necrotizante asociada con Clostridium perfringens en pollos de engorde En este estudio retrospectivo se describen casos inusuales de hepatitis clostridial asociados con una alta mortalidad en pollos de engorde jóvenes. Once casos de hepatitis necrotizante en pollos de engorde de cuatro empresas se enviaron al Centro de Investigación y Diagnóstico Avícola o a la Red de Laboratorios Avícolas del Estado Georgia entre los años 2017 y 2020. En la mayoría de las parvadas, el aumento de la mortalidad a los tres días fue seguido por una mortalidad elevada a los siete días. Las lesiones macroscópicas incluyeron coloración del hígado de verde a marrón oscuro, pulmones congestionados, líquido serosanguinolento en la cara caudoventral del abdomen y enfisema en los sacos vitelinos. En aves mayores de una semana de edad, la enfermedad con signos neurológicos se hizo evidente y consistía en temblores, torticolis (aves como observando a las estrellas) y falta de coordinación. La evaluación histopatológica reveló hepatitis multifocal a fibrinoheterófila coalescente y necrotizante asociada con bacterias grampositivas largas en forma de bastón. Las muestras de hígado fijadas en formalina de seis casos de los ocho casos analizados dieron positivo para Clostridium perfringens por inmunohistoquímica. Las muestras de hígado de dos casos dieron positivo en cultivo para Clostridium spp., y se aisló C. perfringens de una muestra. La tipificación por el tipo de toxina mediante PCR realizado en siete muestras reveló la presencia de los genes que codifican la toxina alfa fosfolipasa C (cpa, plc) y la toxina de enteritis necrótica similar a la toxina B (netB) en seis muestras, así como la citotoxina grande de C. perfringens (tpeL) en una muestra. Se sospecha que las reproductoras de pollos de engorde son la fuente de la infección, y las pruebas revelaron C. perfringens en las muestras de las incubadoras y entre las parvadas de reproductoras de pollos de engorde. La terapia antimicrobiana se combinó con un saneamiento mejorado en la granja y en la incubadora de esa empresa, lo que redujo notablemente la mortalidad y los signos clínicos. Esta es la primera evaluación exhaustiva de la hepatitis necrosante por clostridios en pollitos recién nacidos y la segunda que se ha informado en la literatura.

Controversias en neuroinmunología: esclerosis múltiple, vacunación, SARS-CoV-2 y otros dilemas / Controversies in neuroimmunology: multiple sclerosis, vaccination, SARS-CoV-2 and other dilemas

La neuroinmunología es una disciplina que cada vez amplía más sus horizontes en la comprensión de las enfermedades neurológicas. Contemporáneamente, y a la luz de los nexos fisiopatológicos de las enfermedades neurológicas y la inmunología, se han planteado enfoques diagnósticos y terapéuticos específicos. A pesar de los importantes avances de esta disciplina, existen múltiples dilemas que le conciernen y se filtran en la práctica clínica. En esta revisión, se presentan y discuten 15 controversias, las cuales se construyen con la información clínica disponible más actualizada. Los temas incluidos son: disminución de esteroides en recaídas de esclerosis múltiple; recomendaciones terapéuticas en esclerosis múltiple a la luz de la pandemia por el SARS-CoV-2; evidencia de vacunación en esclerosis múltiple y en otras enfermedades desmielinizantes; panorama actual del síndrome clínico y radiológico aislado; y fallas terapéuticas en esclerosis múltiple; además, criterios para suspender las terapias modificadoras de la enfermedad; evidencia del manejo en recaídas leves; recomendaciones para la profilaxis contra Strongyloides stercolaris; utilidad de un segundo ciclo de inmunoglobulina en el síndrome de Guillain-Barré; criterios para diferenciar una polineuropatía crónica desmielinizante inflamatoria de inicio agudo de un síndrome de Guillain-Barré y, utilidad de la enzima convertidora de angiotensina en neurosarcoidosis. En cada una de las controversias, se presenta la problemática general y se ofrecen recomendaciones específicas que pueden adoptarse en la práctica clínica diaria.

Neuroimmunology is a discipline that increasingly broadens its horizons in the understanding of neurological diseases. At the same time, and in front of the pathophysiological links of neurological diseases and immunology, specific diagnostic and therapeutic approaches have been proposed. Despite the important advances in this discipline, there are multiple dilemmas that concern and filter into clinical practice. This article presents 15 controversies and a discussion about them, which are built with the most up-to-date evidence available. The topics included in this review are: steroid decline in relapses of multiple sclerosis; therapeutic recommendations in MS in light of the SARS-CoV-2 pandemic; evidence of vaccination in multiple sclerosis and other demyelinating diseases; overview current situation of isolated clinical and radiological syndrome; therapeutic failure in multiple sclerosis, as well as criteria for suspension of disease-modifying therapies; evidence of the management of mild relapses in multiple sclerosis; recommendations for prophylaxis against Strongyloides stercolaris; usefulness of a second course of immunoglobulin in the Guillain-Barré syndrome; criteria to differentiate an acute-onset inflammatory demyelinating chronic polyneuropathy versus Guillain-Barré syndrome; and, the utility of angiotensin-converting enzyme in neurosarcoidosis. In each of the controversies, the general problem is presented, and specific recommendations are offered that can be adopted in daily clinical practice.

Does size matter? Two new deletions in the HBB gene cause ß0-thalassemia.

Most ß-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the ß-globin gene that cause ß0-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II ß-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [ß nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with ß0-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the ß-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.

SARS-CoV-2 nucleocapsid protein adheres to replication organelles before viral assembly at the Golgi/ERGIC and lysosome-mediated egress.

Despite being the target of extensive research efforts due to the COVID-19 (coronavirus disease 2019) pandemic, relatively little is known about the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within cells. We investigate and characterize the tightly orchestrated virus assembly by visualizing the spatiotemporal dynamics of the four structural SARS-CoV-2 proteins at high resolution. The nucleoprotein is expressed first and accumulates around folded endoplasmic reticulum (ER) membranes in convoluted layers that contain viral RNA replication foci. We find that, of the three transmembrane proteins, the membrane protein appears at the Golgi apparatus/ER-to-Golgi intermediate compartment before the spike and envelope proteins. Relocation of a lysosome marker toward the assembly compartment and its detection in transport vesicles of viral proteins confirm an important role of lysosomes in SARS-CoV-2 egress. These data provide insights into the spatiotemporal regulation of SARS-CoV-2 assembly and refine the current understanding of SARS-CoV-2 replication.

Hb Nivaria: A New Hemoglobin Variant with a Shortened α-Globin Chain [α139(HC1)Lys→Stop; HBA1: c.418A>T].

We report a novel hemoglobin (Hb) variant found in a Spanish individual from Santa Cruz de Tenerife, the Canary Islands in Spain. The proband was a 39-year-old male. High performance liquid chromatography (HPLC) displayed an unknown peak (19.3%) at a retention time of 1.3 min. eluting before Hb A0. Capillary zone electrophoresis (CZE) showed an abnormal peak (20.0%) in zone 12. Direct DNA sequencing of the α-globin genes revealed heterozygosity for a nonsense mutation at codon 139 (AAA>TAA), causing a lysine to stop codon substitution [α139(HC1)Lys→Stop; HBA1: c.418A>T]. We decided to name the variant Hb Nivaria (Tenerife) for the place of birth and residence of the proband.

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Documento de consenso para el diagnóstico y tratamiento del déficit de piruvato quinasa / Consensus document for the diagnosis and treatment of pyruvate kinase deficiency

El déficit de piruvato quinasa es la segunda enzimopatía más frecuente y la principal causa de anemia hemolítica congénita crónica no esferocítica. Su prevalencia está infraestimada por la baja sospecha clínica de los casos leves, las dificultades del correcto diagnóstico enzimático y la gran variedad de diagnósticos diferenciales. Los avances en las técnicas moleculares están permitiendo mejorar notablemente el diagnóstico. El tratamiento continúa basado en soporte transfusional y esplenectomía, siendo necesarios la vigilancia y el tratamiento de la sobrecarga férrica en todos los pacientes, transfundidos o no. Actualmente el único tratamiento curativo es el trasplante alogénico de progenitores hematopoyéticos, indicado en los casos graves con donante idéntico. Las nuevas terapias farmacológicas y génicas parecen prometedoras. En este artículo, el Grupo Español de Eritropatología realiza una actualización de la situación actual de esta enfermedad, con especial atención a los métodos diagnósticos y a los tratamientos actuales y futuros. (AU)

Pyruvate kinase (PK) deficiency is the second most frequent enzymopathy and the most common cause of chronic hereditary non-spherocytic haemolytic anaemia. Its global prevalence is underestimated due to low clinical suspicion of mild cases, associated with difficulties in the performance and interpretation of PK enzymatic activity assays. With the advent of next generation sequencing techniques, a better diagnostic approach is achieved. Treatment remains based on red blood cell transfusions and splenectomy, with special attention to iron overload, not only in transfusion-dependent patients. Nowadays, allogeneic hematopoietic stem cell transplantation is the only curative treatment, recommended only in selected cases of severely affected patients with an HLA-identical donor. Novel pharmacological and gene therapies are in clinical trials, with promising results. In this article, the Spanish Erythropathology Group reviews the current situation of PK deficiency, paying special attention to the usefulness of different diagnostic techniques and to actual and emerging treatments. (AU)

Aneurisma trombosado de arteria comunicante anterior asociado a síntomas visuales / Thrombosed anterior communicating artery aneurysm associated with visual symptoms

Introducción: Los aneurismas de la arteria comunicante anterior (AComA) se presentan frecuentemente como causa de hemorragia subaracnoidea espontánea (HSAE), en casos raros se asocian a síntomas visuales por compresión mecánica o ruptura y su tratamiento quirúrgico a menudo representa un desafío. Descripción del caso: Se presenta el caso clínico de una paciente adulta con disminución de la agudeza visual del ojo derecho a predominio temporal, y hallazgos en RMN cerebral y angiografía compatibles con un aneurisma grande de AcomA, asociado a trombosis parcial; se realizó clipaje y trombectomía del aneurisma, la panangiografia de control evidenció exclusión completa de la lesión con posterior resolución del déficit visual. Discusión: El déficit visual por un aneurisma de la AcoA se puede generar por varios mecanismos, uno de ellos es la ruptura del aneurisma hacia el nervio óptico, con la subsecuente formación de un hematoma, adherencias y fibrosis; el otro mecanismo es la compresión mecánica de un aneurisma gigante no roto. El manejo quirúrgico a menudo implica técnicas complejas microquirúrgicas para intentar resolver el efecto de masa y excluir el aneurisma. La terapia endovascular es otra alternativa de tratamiento, pero tiene desventajas respecto a la cirugía. Conclusión: Los aneurismas de la AComA en raros casos se pueden asociar a síntomas visuales, debido a que por lo general se romepen cuando son pequeños, y no alcanzan a tener el tamaño suficiente para generar compresión de la vía óptica. Las técnicas microquirúrgicas ofrecen un método efectivo para disminuir el efecto de masa y mejorar los síntomas visuales

Introduction: Aneurysms of the anterior communicating artery (AComA) frequently present as a cause of spontaneous subarachnoid hemorrhage (HSAE), in rare cases they are associated with visual symptoms due to mechanical compression or rupture and their surgical treatment often represents a challenge. Description of the case: We present the clinical case of an adult patient with a decrease in visual acuity due to the right eye with a temporal predominance and findings on brain MRI and angiography compatible with a large AcomA aneurysm associated with partial thrombosis; clipping and thrombectomy of the aneurysm were performed, the control panangiography showed complete exclusion of the lesion. With subsequent resolution of the visual deficit. Discussion: The visual deficit due to an AcoA aneurysm can be generated by several mechanisms, one of them is the rupture of the aneurysm towards the optic nerve, with the subsequent formation of a hematoma, adhesions and fibrosis; The other mechanism is mechanical compression of a giant, unruptured aneurysm. Surgical management often involves complex microsurgical techniques to try to resolve the mass effect and exclude the aneurysm. Endovascular therapy is another treatment alternative, but it has disadvantages compared to surgery. Conclusion: AComA aneurysms in rare cases can be associated with visual symptoms, because they generally rupture when they are small, and are not large enough to generate compression of the optic pathway. Microsurgical techniques offer an effective method to alleviate the mass effect and improve visual symptoms

Characteristics, clinical outcomes, and risk factors of SARS-COV-2 infection in adult acute myeloid leukemia patients: experience of the PETHEMA group.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces higher morbidity and mortality in hematological malignancies, but evidence in acute myeloid leukemia (AML) is scarce. A multicenter observational study was conducted to determine the clinical outcomes and assess the impact of therapeutic approaches in adult AML patients with SARS-CoV-2 infection in the first wave (March-May 2020). Overall, 108 patients were included: 51.9% with active leukemia and 70.4% under therapeutic schedules for AML. Signs and symptoms of SARS-CoV-2 were present in 96.3% of patients and 82.4% received specific treatment for SARS-CoV-2. The mortality rate was 43.5% and was correlated with age, gender, active leukemia, dyspnea, severe SARS-CoV-2, intensive care measures, neutrophil count, and D-dimer levels. A protective effect was found with azithromycin, lopinavir/ritonavir, and normal liver enzyme levels. During the SARS-CoV-2 first wave, our findings suggested an increased mortality in AML in a short period. SARS-CoV-2 management could be guided by risk factors in AML patients.

Task-shifting to optimize outpatient neurological care in Zambia.

OBJECTIVE: To investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping. BACKGROUND: Zambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC). METHODS: We evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task-shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics. RESULTS: From 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurological diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills. CONCLUSIONS: Epilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substantially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.