Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

A Mayan founder mutation is a common cause of deafness in Guatemala.

Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population.

Peach extract induces systemic and local immune responses in an experimental food allergy model.

Peach allergy is among the most frequent food allergies in the Mediterranean area, often eliciting severe anaphylactic reactions in patients. Due to the risk of severe symptoms, studies in humans are limited, leading to a lack of therapeutic options. This study aimed to develop a peach allergy mouse model as a tool to better understand the pathomechanism and to allow preclinical investigations on the development of optimized strategies for immunotherapy. CBA/J mice were sensitized intraperitoneally with peach extract or PBS, using alum as adjuvant. Afterwards, extract was administered intragastrically to involve the intestinal tract. Allergen provocation was performed via intraperitoneal injection of extract, measuring drop of body temperature as main read out of anaphylaxis. The model induced allergy-related symptoms in mice, including decrease of body temperature. Antibody levels in serum and intestinal homogenates revealed a Th2 response with increased levels of mMCPT-1, peach- and Pru p 3-specific IgE, IgG1 and IgG2a as well as increased levels of IL-4 and IL-13. FACS analysis of small intestine lamina propria revealed increased amounts of T cells, neutrophils and DCs in peach allergic mice. These data suggest the successful establishment of a peach allergy mouse model, inducing systemic as well as local gastrointestinal reactions.

Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

[Ischaemic or transient attack? Magnetic resonance imaging in transient ischaemic attack: a review of 106 cases]. / Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.

INTRODUCTION: Transient ischaemic attack (TIA) has classically been defined as an episode of self-limited focal neurological deficit lasting up to 24 hours, with no neuroimaging evidence of established acute ischaemic injury. However, the definition of this entity is changing, and is adapting to new times and new diagnostic techniques, including magnetic resonance imaging (MRI) with diffusion sequences. An early and comprehensive approach to TIA, including MRI, is important to rule out clinically recovered established ischaemic strokes, in order to optimise the diagnostic and therapeutic management of patients. PATIENTS AND METHODS: Patients admitted to our stroke unit over a six-month period with suspected TIA were identified, and the definitive diagnosis and approach was studied based on the tests performed. RESULTS: A sample of 106 suspected cases of TIA were studied, in which early MRI was performed. Of these, 42 (39.62%) were clinically recovered ischaemic strokes (CRIS); 32 (30.18%), other pathologies (six epileptic seizures, five migraine auras, nine functional disorders, two amyloid spells and nine other causes, totalling 31); 26 (24.52%), TIAs; and six (5.66%), haemorrhagic stroke. Of 43 CRIS, eight (18.6%) were cardioembolic; eight (18.6%), atherothrombotic; eight (18.6%), embolic stroke of unknown origin; six (13.95%), lacunar stroke; five (11.62%) of infrequent cause; and four (9.3%), totalling 39, of undetermined cause. CRIS patients received significantly more individualised therapeutic management than TIA patients. CONCLUSIONS: The early use of MRI in the clinical suspicion of TIA makes it possible to gather evidence of CRIS and optimises the diagnostic and therapeutic approach for patients.

TITLE: Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.Introducción. El accidente isquémico transitorio (AIT) clásicamente se ha definido como un episodio de déficit focal neurológico autolimitado con duración máxima de 24 horas, sin evidencia en la neuroimagen de lesión isquémica aguda establecida. Sin embargo, la definición de esta entidad está variando y se está adaptando a los nuevos tiempos y técnicas diagnósticas, incluida la resonancia magnética (RM) con secuencias en difusión. Es importante un abordaje íntegro y precoz del AIT, con RM cerebral, para descartar ictus isquémicos establecidos recuperados clínicamente, y así optimizar el manejo diagnóstico y terapéutico de los pacientes. Pacientes y métodos. Se identificó a los pacientes ingresados en un período de seis meses como sospecha de AIT en nuestra unidad de ictus, y se estudió el diagnóstico definitivo y su abordaje basándose en las pruebas realizadas. Resultados. Se estudiaron 106 sospechas de AIT en las que se realizó una RM precoz. De ellas, 43 (40,57%) fueron ictus isquémicos clínicamente recuperados (IICR); 31 (29,24%), otras patologías (nueve trastornos funcionales, seis crisis epilépticas, cinco auras migrañosas, dos amyloid spells y nueve otras causas); 26 (24,52%), AIT; y seis (5,66%), ictus hemorrágicos. De 43 IICR, ocho (18,6%) fueron cardioembólicos; ocho (18,6%), aterotrombóticos; ocho (18,6%), ictus embólico de origen desconocido; seis (13,95%), lacunares; cinco (11,62%) de causa infrecuente; cuatro (9,3%) microangiopáticos y cuatro (9,3%), de causa indeterminada. Los IICR recibieron un manejo terapéutico significativamente más individualizado respecto a los pacientes con AIT. Conclusiones. El uso de RM precoz en la sospecha clínica de AIT permite evidenciar la existencia de IICR y optimizar el abordaje diagnóstico y terapéutico de los pacientes.

Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

[Comparison between the 1993 and 2002 Guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) for identifying respiratory events in polysomnography tests]. / Comparación entre las normativas de la SEPAR de 1993 y 2002 en la lectura de los eventos respiratorios de las mismas polisomnografías.

OBJECTIVE: To compare the results of applying both the 1993 and 2002 guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) to identify respiratory events during nighttime polysomnography tests. PATIENTS AND METHODS: One hundred twenty consecutive patients with medium to high suspicion of sleep apnea-hypopnea syndrome (SAHS) were included in the study. The 1993 guidelines recommended the use of a thermistor and the evaluation of only apneas and hypopneas. The 2002 guidelines, on the other hand, recommended the use of a thermistor, nasal pressure cannula, and thoracoabdominal bands so that respiratory effort related to arousals could be studied along with apneas and hypopneas. In our study we did not use an esophageal pressure catheter. We calculated the apnea index, hypopnea index, and apnea-hypopnea index (AHI) and determined the number of patients who would be diagnosed with SAHS (AH I > or =10) and the number for whom initiation of continuous positive airway pressure treatment would be recommended (AHI > or =30) according to the 2 sets of guidelines. RESULTS: Polysomnographic tests were valid for 118 of the 120 patients (80% men). The mean (SD) age was 51 (11.6) years and the mean body mass index 31.2 (4.3). Using the 1993 guidelines, the AHI was less than 10 in 25 patients, between 20 and 29 in 38, and 30 or more in 50. In the group overall, mean apnea and hypopnea indices and AHI were all significantly higher with the 2002 guidelines than with the 1993 criteria. With the 1993 criteria, the mean AHI was 33.16 and with 2002 criteria, 45.02 (P<.05). Sixty-four percent of the studies considered normal according to the 1993 SEPAR guidelines were considered apneic according to the 2002 guidelines. Of the patients considered not to need continuous positive airway pressure according to the 1993 SEPAR guidelines, 47.61% did need therapy according to the 2002 guidelines. CONCLUSIONS: There are significant differences in AHI, and in both apnea and hypopnea indices depending on whether the 1993 or the 2002 SEPAR guidelines are applied.

Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression.

Recent data indicate that the heat shock response inhibits nuclear translocation of the proinflammatory transcription factor NF-kappaB. Under basal conditions NF-kappaB is retained in the cytoplasm by an inhibitory protein called I-kappaB which exists as two major isoforms: I-kappaBalpha and I-kappaBbeta. Induction of the heat shock response in BEAS-2B cells, a human cell line representative of bronchial epithelium, increased expression of I-kappaBalpha mRNA in a time-dependent manner. Coincubation with actinomycin-D inhibited heat shock-mediated expression of I-kappaBalpha mRNA. Transient transfection assays with a plasmid containing the reporter gene firefly luciferase, under the control of the human I-kappaBalpha promoter, demonstrated that heat shock activated the I-kappaBalpha promoter. Heat shock-mediated induction of I-kappaBalpha was associated with inhibition of NF-kappaB activation. We conclude that heat shock increases I-kappaBalpha mRNA expression in BEAS-2B cells by activating the I-kappaBalpha promoter, and propose that heat shock-mediated up-regulation of I-kappaBalpha is a potential mechanism by which the heat shock response inhibits proinflammatory responses in lung cells.

Heat shock protein induction protects human respiratory epithelium against nitric oxide-mediated cytotoxicity.

Induction of heat shock proteins (HSPs) confers protection against a variety of cytotoxic agents. We hypothesized that induction of HSPs would protect cultured human respiratory epithelium against nitric oxide (NO)-mediated injury. Incubation of a human bronchial epithelial cell line (BEAS-2B cells) at 43 degrees C for 1.5 h induced expression of several HSPs. Prior induction of HSPs was associated with protection against the NO-donors S-nitroso-N-acetyl penicillamine and 3-morpholinsydnonimine. Protection was evident as improved short term survival and improved ability of cells to recover and proliferate after exposure to NO. Prior induction of HSPs also attenuated NO-mediated decreases in cellular ATP levels, but did not decrease nitrotyrosine formation. Specific overexpression of HSP-70 by plasmid-directed gene transfer protected murine respiratory epithelial cells against S-nitroso-N-acetyl penicillamine. We conclude that in cultured human respiratory epithelium induction of HSPs confers protection against NO-mediated cytotoxicity, possibly by preservation of cellular energetics. We also suggest that HSP-70 may play a specific role in protection.

Ultrastructural and immunocytochemical evidences of core-particle formation in the methylotrophic Pichia pastoris yeast when expressing HCV structural proteins (core-E1).

Particulate antigens of the Hepatitis C virus (HCV) are reported for the first time by transmission electron microscopy in Pichia pastoris. The yeast was cloned to express the first 339 NH2-terminal amino acids of the HCV polyprotein (C-E1.339 polypeptide). The C-E1.339 polypeptide covers the putative 191 aa of the core protein (aa 1-191) and 148 aa of the E1 envelope antigen (aa 192-339). Virus-like particles (VLP) with diameters ranging from 20 nm to 30 nm were specifically observed in those cells expressing the HCV polyprotein. The VLP appeared along the membrane of the endoplasmic reticulum, but were fundamentally localized in vacuoles, either free or inside autophagic bodies. Clustered particles, chains of particles, high-density reticular structures, and crystalloid bodies were also detected, the last one being an orderly arrangement of particles with 20 nm diameters. The crystal-associated particles are well differentiated from the intracellular VLP because of their uniform size and shape. We argue that membrane components are retained in the architecture of the VLP, conferring to this particle certain heterogeneity. Both kinds of particles, the VLP formed after treatment with NP-40 and the crystal-associated particles, were core protein-positives. Whether they reflect mature HCV nucleocapsid or intermediary states in the viral nucleocapsid morphogenesis remains unknown. We conclude that, like mammalian cell lines, the P. pastoris yeast could be an appropriate host for the analysis of HCV polyprotein processing and, eventually, virus assembly.

[Acute renal failure of obstructive etiology caused by uterine prolapse]. / Fracaso renal agudo de etiología obstructiva originado por prolapso uterino.

We describe a 76-year-old woman with severe uterine prolapse with secondary bilateral ureterohydronefrosis and acute renal failure, which improved after the reposition of the uterus. Physiopathological mechanisms and treatment of obstructive uropathy related with uterine prolapse are discussed.

[Analysis of the reasons for visits to a neurology office in Asturias]. / Análisis de los motivos de consulta en una consulta de Neurología de área en Asturias.

INTRODUCTION: In recent years, the out-patient neurological demand has been growing constantly. Many studies exist on the characteristics of this in our country. However, up to date, none of them have been made in the Principality of Asturias. We have proposed to learn the characteristics of the out-patient neurological care in our area and consequently to contribute to an improvement in medical care planning. PATIENTS AND METHODS: The requests for consultation received were collected prospectively over 18 months. Annual demand was calculated using the population data. One thousand patients were finally included in the study. The following data were gathered: age, gender, origin, reason for consultation, and destination. RESULTS: Demand for first visits was 11.94 per 1.000 inhabitants/year. Average age was of 62.04 years, the highest published to date. More women (59%) than men consulted. The most frequent age range was 75-80 years. Headache was the most common condition. Cognitive problems were the most common one in patients over 65 years. Non-neurological problems were the third reason for consultation. A total of 50.4% of the patients were not given an appointment for follow-up. CONCLUSIONS: Mean age of the patients seem in Neurology seems to be progressively increasing and consequently, consultations for cognitive problems, which together with headaches, are the most frequent reason of consultation. A high percentage of non-neurological conditions can be related with a high percentage of discharges.

[Thrombosis of the cavernous sinus following prone-position spinal surgery in a patient with factor V Leiden]. / Trombosis de seno cavernoso tras una cirugía raquídea en decúbito prono en un paciente portador del factor V de Leiden.

INTRODUCTION: Non-infectious thrombosis of the cavernous sinus has sometimes been reported as a complication following neurosurgical procedures and, in one case, after carrying out the operation in a prone position. Factor V Leiden is a genetic risk factor for presenting an intracranial venous thrombotic disease. We report the case of a patient who suffered thrombosis of the cavernous sinus following prolonged surgery in the prone position and in whom a mutation of factor V Leiden in a heterozygotic state was discovered. CASE REPORT: A 64-year-old male, with arterial hypertension as the only known vascular risk factor, who, after prolonged surgery in a prone position, presented amaurosis in the left eye accompanied some hours later by ocular pain, conjunctival ecchymosis, proptosis and abolition of extrinsic ocular mobility. An angiography scan confirmed the existence of thrombosis in the cavernous sinus. Treatment was established with low-molecular-weight heparin without the occurrence of any other kinds of complications. The patient gradually recovered extrinsic ocular mobility but not visual acuity. A heterozygotic mutation for factor V Leiden was found in a hypercoagulability study that was later performed. CONCLUSIONS: The coexistence of a risk factor for presenting a venous thrombotic disease and a mechanical phenomenon, venous statis, due to the posture adopted for the surgical intervention together account for the complication presented by the patient.

[Trisomy 5p due to paternal translocation (4;5) (q35;p12)]. / Trisomía 5p por translocación (4;5) (q35;p12) paterna.

A ten month-old boy had a 5p trisomy secondary to a paternal t(4;5) (p35;p12) translocation. The main stigmata were macrocranium, hydrocephaly, coloboma of the right iris, atrial septal defect, talipes equinovarus, and psychomotor retardation. Overall, the clinical picture was characteristic of the 5p trisomy that includes the band 5p13.

Dermatoglyphics in Saethre-Chotzen syndrome: a family study.

The dermatoglyphic findings in a Cuban family with the Saethre-Chotzen syndrome are reported. The family consisted of the parents who were first cousins and their three children. A new classification of zygodactylous patterns was used. Characteristic dermatoglyphic patterns which appeared in these cases were representative of the syndrome. Dermatoglyphics also helped to discover minor expressions of syndactyly and showed that all the members of the family had zygodactylous patterns on palms and soles.

Sesquiterpene lactones inhibit inducible nitric oxide synthase gene expression in cultured rat aortic smooth muscle cells.

Nitric oxide (NO) is an important regulator and effector molecule in various inflammatory disease states. High output of NO during inflammation is generated by the inducible isoform of nitric oxide synthase (iNOS). Sesquiterpene lactones are derived from Mexican-Indian medicinal plants and are known to have potent anti-inflammatory properties. The mechanisms by which sesquiterpene lactones exert their anti-inflammatory effects are not fully understood. In the current studies we determined if the sesquiterpene lactones, parthenolide and isohelenin, modulate iNOS gene expression in cultured rat aortic smooth muscle cells (RASMC) treated with lipopolysaccharide and interferon-gamma. Treatment with parthenolide or isohelenin inhibited NO production and iNOS mRNA expression in a concentration-dependent manner. Transient transfection studies with an iNOS promoter-luciferase reporter plasmid demonstrated that parthenolide and isohelenin also inhibited activation of the iNOS promoter. Inhibition of iNOS promoter activation was associated with inhibition of both I-kappaBalpha degradation and nuclear translocation of NF-kappaB. Neither parthenolide nor isohelenin induced the heat shock response in RASMC. We conclude that sesquiterpene lactones inhibit iNOS gene expression by a mechanism involving stabilization of the I-kappaBalpha/NF-kappaB complex. This effect is not related to induction of the heat shock response. The ability of sesquiterpene lactones to inhibit iNOS gene expression may account, in part, for their anti-inflammatory effects.