Analysis of viral pneumonia and risk factors associated with severity of influenza virus infection in hospitalized patients from 2012 to 2016.

BACKGROUND: Influenza viruses cause pneumonia in approximately one-third of cases, and pneumonia is an important cause of death. The aim was to identify risk factors associated with severity and those that could predict the development of pneumonia. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during four influenza seasons in Spain (October to May) from to 2012-2016. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included, 93 (14%) of which were severe; 73 (10.9%) were admitted to Intensive Care Unit (ICU), 39 (5.8%) died, and 185 (27.7%) developed pneumonia. Compared to less severe cases, patients with severe disease: were less vaccinated (40% vs. 28%, p = 0.021); presented with more confusion (26.9% vs. 6.8%), were more hypoxemic (Horowitz index (PaO2/FiO2) 261 vs. 280), had higher C-reactive protein (CRP) (12.3 vs. 4.0), had more coinfections (26.8% vs. 6.3%) and had more pleural effusion (14% vs. 2.6%) (last six all p < 0.001). Risk factors significantly associated with severity were pneumonia [OR (95% CI) = 4.14 (2.4-7.16)], history of heart disease (1.84, 1.03-3.28), and confusion at admission (4.99, 2.55-9.74). Influenza vaccination was protective (0.53, 0.28-0.98). Compared to those without pneumonia, the pneumonia group had higher CRP (11.3 vs. 4.0, p < 0.001), lower oxygen saturation (92% vs. 94%, p < 0.001), were more hypoxic (PaO2/FiO2 266 vs. 281, p < 0.001), and incurred more mechanical ventilation, septic shock, admission to the ICU, and deaths (all four p < 0.001). Higher CRP and lower oxygen saturation were independent variables for predicting the development of pneumonia. CONCLUSIONS: Pneumonia, history of heart disease, confusion and no influenza vaccination were independent variables to present complications in patients admitted with influenza infection.

Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome.

The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan). Besides varying levels of intellectual disability, the prevalence of autism spectrum disorders, attention deficit disorders, anxiety disorders, and psychotic disorders in young individuals with 22q11DS is significantly higher than in the general population, or in individuals with idiopathic intellectual disability. Possible explanations for this observed phenotypic variability will be discussed, including genetic pleiotropy, gene-environment interactions, the age-dependency of phenotypes, but also the impact of assessment and ascertainment bias as well as the limitations of our current diagnostic classification system. The implications inferred by these observations aforementioned bear direct relevance to both scientists and clinicians. Observations regarding the neuropsychiatric manifestations in individuals with 22q11DS exemplify the need for a dimensional approach to neuropsychiatric assessment, in addition to our current categorical diagnostic classification system. The potential usefulness of 22q11DS as a genetic model to study the early phases of schizophrenia as well as the phenomenon of neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a clinical perspective, the importance of regular neuropsychiatric evaluations with attention to symptoms not always captured in diagnostic categories and of maintaining equilibrium between individual difficulties and competencies and environmental demands will be discussed.

Knowledge of asthma and anaphylaxis among teachers in Spanish schools.

INTRODUCTION: Allergic diseases affect 15-20% of the paediatric population in the industrialised world. Most educational centres in Spain do not have health professionals among their staff, and the teachers are in charge of child care in school. The advisability of specific training of the teaching staff should be considered, with the introduction of concrete intervention plans in the event of life-threatening emergencies in schools. MATERIAL AND METHODS: Evaluation of the training needs constitutes the first step in planning an educational project. In this regard, the Health Education Group of the Spanish Society of Clinical Immunology, Allergology and Paediatric Asthma (Grupo de Educación Sanitaria de la Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica [SEICAAP]) assessed the knowledge of teachers in five Spanish Autonomous Communities, using a self-administered questionnaire specifically developed for this study. The data obtained were analysed using the SPSS statistical package. RESULTS: A total of 2479 teachers completed the questionnaire. Most of them claimed to know what asthma is, and almost one half considered that they would know how to act in the event of an asthma attack. This proportion was higher among physical education teachers. Most would not know how to act in the case of anaphylaxis or be able to administer the required medication. In general, the teachers expressed interest in receiving training and in having an interventional protocol applicable to situations of this kind. DISCUSSION: It is important to know what the training requirements are in order to develop plans for intervention in the event of an emergency in school. Teachers admit a lack of knowledge on how to deal with these disorders, but express a wish to receive training.

SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement.

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation).

Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures.

BACKGROUND: In vitro cultivation of Plasmodium falciparum is usually carried out through the continuous preservation of infected erythrocytes deposited in static thin layers of settled haematocrit. This technique, called the candle-jar method, was first achieved by Trager and Jensen in 1976 and has undergone slight modifications since then. However, no systematic studies concerning the geometry of the haematocrit layer have been carried out. In this work, a thorough investigation of the effects of the geometric culturing conditions on the parasite's development is presented. METHODS: Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model. CONCLUSION: In line with the results, a mechanism governing the propagation of the infection which limits it to the vicinity of the interface between the haematocrit layer and the culture medium is deduced, and the most appropriate configurations are proposed for further experimental assays.

The structure of a eukaryotic nicotinic acid phosphoribosyltransferase reveals structural heterogeneity among type II PRTases.

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for cellular redox reactions and can act as an important substrate in numerous biological processes. As a result, nature has evolved multiple biosynthetic pathways to meet this high chemical demand. In Saccharomyces cerevisiae, the NAD salvage pathway relies on the activity of nicotinic acid phosphoribosyltransferase (NAPRTase), a member of the phosphoribosyltransferase (PRTase) superfamily. Here, we report the structure of a eukaryotic (yeast) NAPRTase at 1.75 A resolution (locus name: YOR209C, gene name: NPT1). The structure reveals a two-domain fold that resembles the architecture of quinolinic acid phosphoribosyltransferases (QAPRTases), but with completely different dispositions that provide evidence for structural heterogeneity among the Type II PRTases. The identification of a third domain in NAPRTases provides a structural basis and possible mechanism for the functional modulation of this family of enzymes by ATP.

Ex vivo trypanocidal activity of 1-(2-hydroxybenzylidene)thiosemicarbazide against Trypanosoma equiperdum.

Trypanosoma equiperdum is the causative agent of dourine, a venereal disease in horses and donkeys. This parasite has a widely distribution, is found in Africa, Asia, Southern and Eastern Europe, Russia, Mexico and Venezuela. The T. equiperdum is morphologically indistinguishable to other Trypanozoon species, however differs from other mammalian trypanosomes due to the fact that it is primarily a tissue parasite, generating cutaneous plaques, swelling of genitalia and neurological signs. The aim of this study was to evaluate the trypanocidal effectiveness of a set of derivatives of thiosemicarbazones on a T. equiperdum ex vivo culture. All compounds appeared to have trypanocidal activity, however one of them shown better solubility and a dose-dependent effect. The median inhibitory concentration (IC50) was 1.2µM. The selected compound exhibits a greater inhibitory activity than diminazene aceturate, a common drug for animal trypanosomosis treatment.

Comparative structural analysis of a novel glutathioneS-transferase (ATU5508) from Agrobacterium tumefaciens at 2.0 A resolution.

Glutathione S-transferases (GSTs) comprise a diverse superfamily of enzymes found in organisms from all kingdoms of life. GSTs are involved in diverse processes, notably small-molecule biosynthesis or detoxification, and are frequently also used in protein engineering studies or as biotechnology tools. Here, we report the high-resolution X-ray structure of Atu5508 from the pathogenic soil bacterium Agrobacterium tumefaciens (atGST1). Through use of comparative sequence and structural analysis of the GST superfamily, we identified local sequence and structural signatures, which allowed us to distinguish between different GST classes. This approach enables GST classification based on structure, without requiring additional biochemical or immunological data. Consequently, analysis of the atGST1 crystal structure suggests a new GST class, distinct from previously characterized GSTs, which would make it an attractive target for further biochemical studies.

Functional analysis of substrate and cofactor complex structures of a thymidylate synthase-complementing protein.

Like thymidylate synthase (TS) in eukaryotes, the thymidylate synthase-complementing proteins (TSCPs) are mandatory for cell survival of many prokaryotes in the absence of external sources of thymidylate. Details of the mechanism of this novel family of enzymes are unknown. Here, we report the structural and functional analysis of a TSCP from Thermotoga maritima and its complexes with substrate, analogs, and cofactor. The structures presented here provide a basis for rationalizing the TSCP catalysis and reveal the possibility of the design of an inhibitor. We have identified a new helix-loop-strand FAD binding motif characteristic of the enzymes in the TSCP family. The presence of a hydrophobic core with residues conserved among the TSCP family suggests a common overall fold.

Protein biophysical properties that correlate with crystallization success in Thermotoga maritima: maximum clustering strategy for structural genomics.

Cost and time reduction are two of the driving forces in the development of new strategies for protein crystallization and subsequent structure determination. Here, we report the analysis of the Thermotoga maritima proteome, in which we compare the proteins that were successfully expressed, purified and crystallized versus the rest of the proteome. This set of almost 500 proteins represents one of the largest, internally consistent, protein expression and crystallization datasets available. The analysis shows that individual parameters, such as isoelectric point, sequence length, average hydropathy, low complexity regions (SEG), and combinations of these biophysical properties for crystallized proteins define a distinct subset of the T. maritima proteome. The distribution profiles of the various biophysical properties in the expression/crystallization set are then used to extract rules to improve target selection and improve the efficiency and output of structural genomics, as well as general structural biology efforts.

Conformational differences among solution structures of the type Ialpha, IIalpha and IIbeta protein kinase A regulatory subunit homodimers: role of the linker regions.

The regulatory (R) subunits of the cAMP-dependent protein kinase (protein kinase A or PKA) are multi-domain proteins responsible for conferring cAMP-dependence and localizing PKA to specific subcellular locations. There are four isoforms of the R subunit in mammals that are similar in molecular mass and domain organization, but clearly serve different biological functions. Although high-resolution structures are available for the cAMP-binding domains and dimerization/docking domains of two isoforms, there are no high-resolution structures of any of the intact R subunit homodimer isoforms. The results of small-angle X-ray scattering studies presented here indicate that the RIalpha, RIIalpha, and RIIbeta homodimers differ markedly in overall shape, despite extensive sequence homology and similar molecular masses. The RIIalpha and RIIbeta homodimers have very extended, rod-like shapes, whereas the RIalpha homodimer likely has a compact Y-shape. Based on a comparison of the R subunit sequences, we predict that the linker regions are the likely cause of these large differences in shape among the isoforms. In addition, we show that cAMP binding does not cause large conformational changes in type Ialpha or IIalpha R subunit homodimers, suggesting that the activation of PKA by cAMP involves only local conformational changes in the R subunits.

A single dose of granulocyte colony-stimulating factor modifies radiation-induced death in B6D2F1 mice.

Granulocyte colony stimulating factor (G-CSF) stimulates the proliferation of progenitor cells committed to myeloid differentiation. In animal models, G-CSF is able to stimulate granulocyte recovery and promote survival after lethal or sublethal irradiation when administered as daily injections, suggesting an influence on the residual hematopoietic primitive precursors surviving irradiation. In this study, we clearly demonstrate that a single dose of G-CSF (1 mg/kg) administered to B6D2F1 mice 2 hours after a lethal dose 95/30 irradiation achieves a 78% survival at day +30 after irradiation. Survival of G-CSF treated mice compares favourably with that of syngenic bone marrow transplantation recipients (78% vs 90%, ns).

Knowledge and Attitude of Health Personnel at the Garraf Health Consortium Regarding Donation and Transplantation.

INTRODUCTION: The main objective of this study was to determine the attitude and knowledge regarding donation and transplantation of the medical and nursing staff at a community hospital in the province of Barcelona. METHODS: This is descriptive, cross-sectional observational study was conducted in the Garraf Health Consortium, a second-level community hospital located in Sant Pere de Ribes. The study population consisted wholly of health professionals who agreed to participate voluntarily in the study. To determine the attitude and knowledge regarding donation and transplantation, a questionnaire was designed, consisting of 36 items divided into 3 sections: data on attitudes, knowledge about donation and transplantation, and sociodemographic and work-related data. We distributed 380 questionnaires; 236 were returned (62.10%). RESULTS: A total of 70.8% of respondents said they would like to be an organ and tissue donor compared with 1.7% who did not want to be a donor (mainly for fear of inferior medical care, for religious reasons, or both). Among the respondents, 98.7% agree with organ donation, 58.8% were not sure about the criteria for inclusion in the waiting list of Spain, and 69.1% agreed with the view that brain death is equivalent to death. CONCLUSIONS: We found a positive attitude toward donation and transplantation in the hospital, but more knowledge is needed to increase the donation rate.

Infectious spondylitis in the Balearic Islands: An analysis of 51 cases. / Espondilitis infecciosa en Baleares: análisis de 51 casos.

INTRODUCTION: Vertebral osteomyelitis (VO) is a rare entity, although its incidence has increased in recent years. The objective is to describe the patients with this infection in our environment and a comparison with other published series. METHODS: A retrospective review was conducted of epidemiological, clinical, microbiological, treatment, complications and evolution data of patients with VO during 10 years (2004-2014) in two hospitals of Mallorca. RESULTS: 51 cases, median age 66 (range 22-85) years, 37 (72.5%) men with a mean onset of symptoms of 80.1 ± 125.1 days. In thirty-six (70.6%) cases the origin of infection was considered hematogenous, although previous bacteremia was documented in 23 (45%) cases, being of urinary in 10 (43.5%) cases. Clinically at the moment of diagnosis 35 (68.8%) had fever, 32 (62.7%) pain, 14 (27.5%) irradiated nerve pain and 10 (19.6%) paralysis/paresia. MRI was the most performed radiological test 46 (90.2%), being pathological in all cases. S. aureus 23 (52.3%) was the most common microbiological isolates. At the moment of the diagnosis, blood cultures were positive in 27 (65.8%) of 41 cases and 11 (50%) of 22 percutaneous puncture was positive. Paraspinal, epidural or psoas abscesses were observed in 23 (45.1%), neurological deficit in 7 (13.7%) and chronic pain in 6 (11.8%). One patient (1.9%) died in relation with infection. CONCLUSIONS: Diagnosis was delayed in most cases. Previous bacteremia being main predisposing factor and hematogenous origin the main source of infection. S. aureus was the most isolated. Percutaneous puncture together with blood cultures increase etiologic diagnosis. A high percentage of patients had complications or sequelae.

Predicted role for the archease protein family based on structural and sequence analysis of TM1083 and MTH1598, two proteins structurally characterized through structural genomics efforts.

Recently, the structures of two proteins belonging to the archease family, TM1083 from Thermotoga maritima and MTH1598 from Methanobacterium thermoautotrophicum, have been solved independently by two Protein Structure Initiative structural genomics pilot centers using X-ray crystallography and NMR, respectively. The archease protein family is a good example of one of the paradoxes of structural genomics: Approximately one third of protein structures produced by structural genomics centers have no known function and are still annotated as "hypothetical proteins" in the Protein Data Bank. In the case of archeases, despite the existence of two protein structures and abundant sequence information, there is still no function assigned to this protein family. Here, our group predicts, based on structural similarity, sequence conservation, and gene context analyses, that members of this protein family might function as chaperones or modulators of proteins involved in DNA/RNA processing. The conservation of genomic context for this protein family is constant from Archaea and Bacteria to humans, and suggests that unannotated open reading frames contiguous to them could be novel RNA/DNA binding proteins.

In silico study of breast cancer associated gene 3 using LION Target Engine and other tools.

Sequence analysis of individual targets is an important step in annotation and validation. As a test case, we investigated human breast cancer associated gene 3 (BCA3) with LION Target Engine and with other bioinformatics tools. LION Target Engine confirmed that the BCA3 gene is located on 11p15.4 and that the two most likely splice variants (lacking exon 3 and exons 3 and 5, respectively) exist. Based on our manual curation of sequence data, it is proposed that an additional variant (missing only exon 5) published in a public sequence repository, is a prediction artifact. A significant number of new orthologs were also identified, and these were the basis for a high-quality protein secondary structure prediction. Moreover, our research confirmed several distinct functional domains as described in earlier reports. Sequence conservation from multiple sequence alignments, splice variant identification, secondary structure predictions, and predicted phosphorylation sites suggest that the removal of interaction sites through alternative splicing might play a modulatory role in BCA3. This in silico approach shows the depth and relevance of an analysis that can be accomplished by including a variety of publicly available tools with an integrated and customizable life science informatics platform.

[Role of aeroallergens in the etiopathogenesis of atopic dermatitis]. / Importancia de los aeroalergenos en la etiopatogenia de la dermatitis atópica.

UNLABELLED: Atopic dermatitis is a chronic relapsing inflammatory skin disease. It is most frequent in childhood and its clinical manifestations vary with age. The etiopathogenic mechanisms that explain this process are still poorly understood; several studies performed in adults speculate on the possible role of aeroallergens through direct contact with the skin but, because the etiology of this disease varies with age, studies in children of different ages are required. AIMS: (i) To determine whether children with atopic dermatitis are sensitized to inhalant allergens. (ii) To determine whether these inhalant allergens cause dermatitis or whether they provoke allergic respiratory disease (asthma, rhinitis) concomitant with atopic dermatitis. (iii) To evaluate whether sensitization to a particular allergen takes place at any age or whether there are differences according to age. MATERIAL AND METHODS: This study was performed in the following groups: (i) 64 children with atopic dermatitis, divided into two subgroups, one consisting of 37 children who also presented allergic respiratory disease (asthma, rhinitis) (AR) and another subgroup of 27 patients who presented atopic dermatitis only. (ii) CONTROL GROUP: eight children who presented AR only, to determine whether this group reacted to patch testing with inhalant allergens. (iii) CONTROL GROUP: seven healthy children to rule out non-specific positive tests in the non-atopic population. All groups were divided by age according to the phases of atopic dermatitis: early childhood phase (< 2 years): 21, childhood phase (2-10 years): 37, adolescent phase (> 10 years): 21. In all children total serum IgE determination (RIA), allergen-specific IgE determination (RAST), prick- and patch test were performed. In the three tests the same allergens were used, consisting of the usual components of standardized inhalant and food allergens. When the results of patch testing were positive, biopsy and histopathological analysis were performed and monoclonal antibodies were used to determine reproducibility of the eczematous lesion. RESULTS: Sensitization was found to differ among patients with atopic dermatitis according to whether they presented respiratory symptoms and according to age with a clear predominance of food sensitization in the group aged less than 2 years. In the group aged 2-10 years, mixed sensitization predominated, mainly because of simultaneous respiratory involvement, but it is highly probably that inhalant allergens participate in the etiopathogenesis of atopic dermatitis. In children aged more than 10 years sensitization to inhalant allergens predominated as most presented respiratory symptoms. Patch testing was positive in 34.3 % of patients with atopic dermatitis and approximately half were positive to dust mites. The patch test is of great diagnostic value in atopic dermatitis and none of the tests were positive in the control group. All the biopsies of patch tests with inhalant allergens reproduced the lesions typical of eczema, demonstrating their involvement in the etiopathogenesis of dermatitis.

[Half-body irradiation. Palliative efficacy and predictive factors of response in 78 procedures]. / Irradiación hemicorporal. Eficacia paliativa y factores predictivos de la respuesta en 78 procedimientos.

BACKGROUND: Assessment of palliative effect of hemibody irradiation (HBI) and response-related factors. METHODS: Analysis of prospective collected data of 78 procedures on 71 patients with multiple symptomatic bone metastases, treated with 6 Gy (upper half-body) or 8 Gy (lower half-body) HBI in single fraction. Clinical improvement was quantified by self-evaluation on a visual analogic scale (SVAS) before HBI, and at 24, 48 and 72 hours, at 7 days, and at each monthly control until patient's death. Univariate analysis included: sex, Karnofsky's index, tumor origin, histology, HBI dose, and SVAS before treatment. For statistical purposes the significance level was 0.05. RESULTS: Complete (37.5%) or partial responses were observed in 72/78 (92.3%) procedures, 80% appearing during the first 72 hours. Difference between mean SVAS, before and after treatment (7.7 +/- 1.5 vs 2.8 +/- 2.5), was statistically significant (p < 0.001). A mean response duration of 101 days over a mean overall survival of 141 days implies the 70% of expected patient's life span. Any analyzed prognostic factor does not correlate significantly with HBI response. CONCLUSIONS: HBI is a powerful palliative treatment in patients with multiple symptomatic bone metastasis.

[Site of care provision, etiology and treatment of community-acquired pneumonia in Palma de Mallorca]. / Lugar de atención, etiología y tratamiento de las neumonías adquiridas en la comunidad de Palma de Mallorca.

BACKGROUND: It is not common that community-acquired pneumonias studies include patients non treated in hospital. The objectives were: to determine the cases managed in the ambulatory setting; to describe the clinical features; to identify the aetiological agents, and to describe the treatment, comparing inpatients with outpatients. PATIENTS AND METHODS: Observational prospective study. Population attended at three teaching primary care centers of Palma de Mallorca (60,450 habitants). Patients (> 14 years) were investigated when diagnosticated of community-acquired pneumoniae, from November 1992 to December 1994. Exclussions: HIV infection, patients living in a nursing home and tuberculosis. Data were collected in both Hospital and primary health care centers. Epidemiological, clinical, radiological and laboratory findings were recorded at the initial visit and 21 days after. RESULTS: 91 cases were investigated. 57% were managed at the primary care centers exclusively, 63.3% of the patients who went initially to the hospital were admitted in; but only 10.9% of those who went initially to the primary care centers (p < 0.005). 24 patients were hospitalized. 56 microbiological agents were identified in 48 patients (52.7%): Mycoplasma pneumoniae (10); Streptococcus pneumoniae (9); Influenza B (8); Chlamydia psittacci (7); Influenza A (7); Coxiella burnetii (5); Chlamydia pneumoniae (4); Legionella (3); Adenovirus (2); and Parainfluenza 3 (1). Mycoplasma was predominant in outpatients: 9 cases. S. pneumoniae in inpatients: 5 cases. Eritromycin was the most common treatment prescribed (76.9% of patients), alone or in combination with other antibiotics. Monotherapy was most common at primary care yield (96.7%) than at the hospital (45.2%) (p < 0.005). CONCLUSIONS: Most of the patients with community-acquired pneumonias are managed at primary health care centers. M. pneumoniae is the predominant microbiological agent in outpatients and S. pneumoniae in inpatients. Erithromycin is the most used antibiotic in both groups of patients.