Local-scale Arctic tundra heterogeneity affects regional-scale carbon dynamics.

In northern Alaska nearly 65% of the terrestrial surface is composed of polygonal ground, where geomorphic tundra landforms disproportionately influence carbon and nutrient cycling over fine spatial scales. Process-based biogeochemical models used for local to Pan-Arctic projections of ecological responses to climate change typically operate at coarse-scales (1km2-0.5°) at which fine-scale (<1km2) tundra heterogeneity is often aggregated to the dominant land cover unit. Here, we evaluate the importance of tundra heterogeneity for representing soil carbon dynamics at fine to coarse spatial scales. We leveraged the legacy of data collected near Utqiagvik, Alaska between 1973 and 2016 for model initiation, parameterization, and validation. Simulation uncertainty increased with a reduced representation of tundra heterogeneity and coarsening of spatial scale. Hierarchical cluster analysis of an ensemble of 21st-century simulations reveals that a minimum of two tundra landforms (dry and wet) and a maximum of 4km2 spatial scale is necessary for minimizing uncertainties (<10%) in regional to Pan-Arctic modeling applications.

Assessment of Confirmed Clinical Hypersensitivity to Rituximab in Patients Affected with B-Cell Neoplasia.

Rituximab hypersensitivity reactions are rare but are one of the main causes of rituximab elimination from antilymphoma immunochemotherapy treatments. While the clinical picture may be indistinguishable from other infusion-related reactions, hypersensitivity reactions (HSR) do not disappear and instead become more intense with subsequent administrations. Objective. To describe the use of the 12-step protocol for desensitization to intravenous rituximab in clinical practice and the complementary study of a possible IgE-mediated HSR in the context of B-cell lymphoma treatment. Methods. A 12-step rituximab desensitization protocol was performed prospectively within clinical practice in 10 patients with a history of severe infusion reactions or in patients who had a repeated reaction at subsequent doses despite taking more intense preventive measures. Skin prick tests were performed at the time of reaction and at a later time to eliminate false negatives due to possible drug interference. Results. Overall, with the desensitization protocol, 70% of patients were able to complete the scheduled immunochemotherapy. Two patients had to discontinue the therapy due to clinical persistence and the third due to lymphoma progression. Intradermal tests with 0.1% rituximab were positive in only 20% of cases, demonstrating a mechanism of hypersensitivity. Conclusions. The 12-step desensitization protocol is very effective and assumable within healthcare practice. There is a need to determine the mechanism underlying the infusion reaction in a large proportion of cases due to the risk of future drug exposure.

[Appropriateness of antimicrobial prescriptions in the emergency department of a tertiary hospital]. / Adecuación de las prescripciones antimicrobianas realizadas en el área de urgencias de un hospital de tercer nivel.

OBJECTIVE: Antibiotics are widely prescribed in the Emergency Department (ED), representing 26-62% of outpatient antibiotic prescriptions. Around 40% of antibiotic prescriptions in hospitalized patients are inappropriate or unnecessary. The aim of the study was to assess the appropriateness of antibiotic prescriptions according to local empirical antibiotic treatment guidelines, in the ED of a tertiary hospital. METHODS: Observational, retrospective study including patients attending the ED in November 2016, with an antibiotic prescription, excluding those from residents. RESULTS: A total of 676 patients were included, 57.1% women, mean age 47.4 ± 21.2 years. Patient's diagnoses were 27.2% urinary tract infections (UTI), 24.1% lower respiratory tract infections, 15.4% skin and soft tissue infections (SSTI), 13.8% upper respiratory tract infections, 11.8% oral infections, 2.7% genital/sexually transmitted infections, 1.6% gastrointestinal infections, 0.3% ocular infections and 3.1% other. The most prescribed antibiotic families were: 44.1% penicillins, 21.3% fluoroquinolones. The most prescribed antibiotics were: fosfomycin trometamol in UTI (32.1%), levofloxacin in lower respiratory tract (46.2%) and amoxicillin/clavulanate in oral infections (71.6%), SSTI (62.5%) and upper respiratory tract (46.6%). In 56.8% (384) of the prescriptions antibiotics were indicated. An appropriated antibiotic was selected in 62% (238) of the prescriptions. Appropriated dosage and duration were selected in 82.8% (197) and 45.4% (108) of the prescriptions, respectively. CONCLUSIONS: Appropriateness of antibiotic prescriptions was low, mainly due to an overuse of antibiotics when not indicated, broad spectrum and incorrect treatment duration. These data reinforce the need to enhance adherence to local empirical antibiotic treatment guidelines by developing an antimicrobial stewardship program in the ED.

Evaluating the effect of integrated microfinance and health interventions: an updated review of the evidence.

BACKGROUND: Solutions delivered within firm sectoral boundaries are inadequate in achieving income security and better health for poor populations. Integrated microfinance and health interventions leverage networks of women to promote financial inclusion, build livelihoods, and safeguard against high cost illnesses. Our understanding of the effect of integrated interventions has been limited by variability in intervention, outcome, design, and methodological rigour. This systematic review synthesises the literature through 2015 to understand the effect of integrated microfinance and health programs. METHODS: We searched PubMed, Scopus, Embase, EconLit, and Global Health databases and sourced bibliographies, identifying 964 articles exclusive of duplicates. Title, abstract, and full text review yielded 35 articles. Articles evaluated the effect of intentionally integrated microfinance and health programs on client outcomes. We rated the quality of evidence for each article. RESULTS: Most interventions combined microfinance with health education, which demonstrated positive effects on health knowledge and behaviours, though not health status. Among programs that integrated microfinance with other health components ( i.e. health micro-insurance, linkages to health providers, and access to health products), results were generally positive but mixed due to the smaller number and quality of studies. Interventions combining multiple health components in a given study demonstrated positive effects, though it was unclear which component was driving the effect. Most articles (57%) were moderate in quality. DISCUSSION: Integrated microfinance and health education programs were effective, though longer intervention periods are necessary to measure more complex pathways to health status. The effect of microfinance combined with other health components was less clear. Stronger randomized research designs with multiple study arms are required to improve evidence and disentangle the effects of multiple component microfinance and health interventions. Few studies attempted to understand changes in economic outcomes, limiting our understanding of the relationship between health and income effects.

Diadenosine tetraphosphate induces tight junction disassembly thus increasing corneal epithelial permeability.

BACKGROUND AND PURPOSE: Here, we have studied the effects of the dinucleotide P(1), P(4)-Di (adenosine-5') tetraphosphate (Ap4 A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency. EXPERIMENTAL APPROACH: Experiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4 A (100 µM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y(2) receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens-1 (ZO-1) staining. The hypotensive compound 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5-MCA-NAT, P2Y receptor antagonists and P2Y2 siRNAs. KEY RESULTS: Two hours after Ap4 A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y(2) siRNAs. In vivo, topical application of Ap4 A disrupted ZO-1 membrane distribution. 5-MCA-NAT levels in the aqueous humour were higher when Ap4 A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y(2) siRNA. CONCLUSIONS AND IMPLICATIONS: Ap4 A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency.

[Factors related to dissatisfaction and anger in parents of children treated at paediatric emergency services]. / Factores desencadenantes de insatisfacción e ira en padres de niños atendidos en servicios de urgencias pediátricos.

AIM: Anger in patients and relatives is very frequent in health emergency services and is often associated with aggressiveness and emotional alterations. The aim of the present study is to explore anger in parents while their children are receiving care in paediatric emergency services, seeking the specific dimensions of dissatisfaction that may predict the onset of anger in parents. MATERIALS AND METHODS: A cross-sectional descriptive study using a self-report questionnaire in 711 parents of children seen in paediatric emergency departments. The self-report questionnaires used were the State-Trait Anger Expression Inventory-2 (STAXI-2) and the Satisfaction with Healthcare Services Scale. The statistical analysis included descriptive, correlational, variance and multiple linear regression models. RESULTS: A total of 53 parents (7,5%) showed a moderate or high anger level. The mean score for satisfaction was 37.12 (SD=7.33). It was found that higher levels of overall satisfaction were significantly associated with lower levels of anger (r=-.29, p=.00). Among the variables studied, dissatisfaction with access to the service (ß=-.172, p=.00), with the healthcare staff (ß=-.121, p=.01), and perceived severity of the child's health status (ß=.157, p=.00) predicted higher levels of anger. CONCLUSIONS: On the basis of our results, it is important to continue working to substantially improve access for patients and their families to the emergency department, as well as the information and communication process with the healthcare staff should be included in intervention initiatives.

Bortezomib como alternativa en el tratamiento de pacientes con gammapatías malignas / Bortezomib as an alternative in the treatment of patients with malignant gammopathy

Objetivo: Describir el uso de bortezomib en un hospital comarcal como alternativa en el tratamiento de gammapatías malignas. Métodos: Análisis retrospectivo de los pacientes tratados con bortezomib en nuestro hospital desde noviembre de 2005 hasta octubre de 2007. A partir de la revisión de las historias clínicas de los pacientes se recogieron los datos correspondientes al diagnóstico, tratamientos previos a bortezomib, fecha de la última progresión de la enfermedad, número de ciclos de bortezomib, respuesta a éste, super vivencia global y libre de progresión, complicaciones y efectos secundarios. Resultados: El 47% de los pacientes estudiados eran varones (5/12), con una mediana de edad de 67 años (rango, 40-81 años). El diagnóstico principal fue mieloma múltiple, solo o asociado a plasmocitoma. El inicio con bortezomib coincidió con la última progresión de la enfermedad en el 83% de los pacientes (10/12). El 50% completó 7-8 ciclos con bortezomib. Se obtuvo respuesta en el 58% de los pacientes (7/12), alcanzándose criterios de respuesta parcial en el 33% (4/12) y respuesta completa en el 25% (3/12). Las reacciones adversas más frecuentes fueron neuropatía y toxicidad gastrointestinal, y supuso la suspensión del tratamiento en el 50% de los casos. Conclusiones: Según los resultados obtenidos, bortezomib es una buena alternativa en el tratamiento de las gammapatías malignas, sobre todo en el caso de plasmocitomas (AU)

Objective: To describe the use of bortezomib in a district hospital as an alternative in the treatment of malignant gammopathy. Methods: A retrospective analysis was carried out on patients treated with bortezomib in our hospital between November 2005 and October 2007. The patients’ medical histories were used to obtain data regarding diagnosis, treatments prior to bortezomib, date of the last disease progression, number of bortezomib courses, response to bortezomib, overall and event free survival. Results: 47% of the patients studied were male (5/12). The medianage was 67, (age range between 40 and 81). The main diagnosis was multiple myeloma on its own or associated with plasmocytoma. Bortezomib initiation coincided with the last disease progression in 83%of patients (10/12). 50% of the patients completed 7-8 courses of bortezomib. Response was seen in 58% of the patients (7/12), partial response in 33% of them (4/12) and complete response in 25%(3/12). The most common adverse reactions were neuropathy and gastrointestinal toxicity which required treatment to be discontinued in 50% of cases. Conclusions: According to the results obtained, bortezomib is a good alternative in the treatment of malignant gammopathy, above all in the case of plasmocytomas (AU)

Improved lentiviral vectors for Wiskott-Aldrich syndrome gene therapy mimic endogenous expression profiles throughout haematopoiesis.

Wiskott-Aldrich syndrome (WAS) gene therapy requires highly efficient and well-controlled vectors. Here we studied the performance of a lentiviral vector (LV) harbouring a 500-bp fragment of the WAS proximal promoter (WW), which we previously characterized as haematopoietic-specific and capable of restoring WAS phenotype in patients' T cells. We used an LV (WE) expressing eGFP to evaluate whether this promoter was following the expression pattern of endogenous WASp. Transgene expression was analysed in WE-transduced hCD34+ population and its progeny after in vitro and in vivo differentiation in the Rag2-/-, gammac-/- humanized mouse. We revealed very poor expression from the WE internal promoter in macrophages and erythroid cells. Therefore, we designed a novel LV including a fragment of the alternative WAS promoter in WE vector (AWE). This new vector sustained high transgene levels along the whole lymphoid lineage in vivo. Most importantly, the performance of AWE vector was highly superior to WE vector since AWE clearly improved transgene levels in in vitro and in vivo hCD34+-derived macrophages, erythroid cells, megakaryocytes and B cells while supporting a high expression in human T cells. This emphasizes that it is a suitable LV backbone for gene therapy of haematopoietic diseases such as WAS.

[Bortezomib as an alternative in the treatment of patients with malignant gammopathy]. / Bortezomib como alternativa en el tratamiento de pacientes con gammapatías malignas.

OBJECTIVE: To describe the use of bortezomib in a district hospital as an alternative in the treatment of malignant gammopathy. METHODS: A retrospective analysis was carried out on patients treated with bortezomib in our hospital between November 2005 and October 2007. The patients' medical histories were used to obtain data regarding diagnosis, treatments prior to bortezomib, date of the last disease progression, number of bortezomib courses, response to bortezomib, overall and event free survival. RESULTS: 47% of the patients studied were male (5/12). The median age was 67, (age range between 40 and 81). The main diagnosis was multiple myeloma on its own or associated with plasmocytoma. Bortezomib initiation coincided with the last disease progression in 83% of patients (10/12). 50% of the patients completed 7-8 courses of bortezomib. Response was seen in 58% of the patients (7/12), partial response in 33% of them (4/12) and complete response in 25% (3/12). The most common adverse reactions were neuropathy and gastrointestinal toxicity which required treatment to be discontinued in 50% of cases. CONCLUSIONS: According to the results obtained, bortezomib is a good alternative in the treatment of malignant gammopathy, above all in the case of plasmocytomas.

Nitrogenous compounds of interest in clinical nutrition.

The term "conditionally essential" (or semi-essential), initially applied to amino acids, has been generalized to other nutrients. A conditionally essential nutrient is a compound usually produced in adequate amounts by endogenous synthesis but that is exogenously required under certain circumstances. Thus, arginine, glutamine, cysteine, glycine, carnitine, choline, and polyamines are conditionally essential compounds. In addition, dietary nucleotides are considered semi-essential since some rapidly growing tissues such as the gut, bone marrow, and lymphocytes, preferentially use preformed purine and pyrimidine bases for nucleic acid synthesis. This review discusses the study of conditionally essential nitrogenous nutrients of interest in clinical nutrition. Among them we highlight arginine, involved in endothelial, immune, gastrointestinal, and renal functions, in reproduction, neonatal development, wound healing, and tumorigenicity; glutamine, necessary for maintaining bowel integrity, and with beneficial effects on catabolic states such as sepsis, infection, trauma, and cancer; and nucleotides, implicated in cell growth and differentiation, and with various effects on lipid metabolism, intestinal microbiota, and immune system.

Exogenous nucleosides modulate the expression of rat liver extracellular matrix genes in single cultures of primary hepatocytes and a liver stellate cell line and in their co-culture.

BACKGROUND & AIMS: We have previously reported the antifibrotic effect of dietary nucleotides in cirrhotic rats. In this work, we used primary rat hepatocytes, a liver stellate cell line (CFSC-2G) and co-cultures of both cell types to investigate the effects of exogenous nucleosides on the gene expression of various extracellular matrix components and on markers of liver function, and to ascertain whether the effects found in vivo are due to CFSC-2G, hepatocytes, or are the consequence of cell-cell interactions. RESULTS: Nucleosides enhanced fibronectin, laminin, and alpha1(I) procollagen levels in CFSC-2G and hepatocytes, as well as collagen synthesis and secretion in CFSC-2G. In contrast, nucleosides lowered fibronectin, laminin and alpha1(I) procollagen levels, and decreased collagen synthesis in co-cultures. Matrix metalloproteinase-13 content and collagen secretion increased in co-cultures incubated with nucleosides. Albumin increased in hepatocytes and co-cultures incubated in the presence of nucleosides. CONCLUSIONS: Nucleosides modulate the production of extracellular matrix in single cultures of hepatocytes and of CFSC-2G, and in co-cultures. This effect seems to be regulated at the translational level. The opposite behavior of single cultures and co-cultures is probably due to the fact that the latter model reproduces many of the physical and functional relationships observed in vivo between hepatocytes and stellate cells.

IgE-dependent expression of mRNA for IL-4 and IL-5 in human lung mast cells.

By using the reverse transcriptase (RT)-PCR and in situ hybridization we have studied the expression of mRNA for IL-5 and IL-4 in human lung mast cells induced by cross-linkage of high affinity Fc epsilon Rs. Lung mast cells were purified using affinity magnetic selection with mAb YB5.B8 against c-kit to achieve a final mast cell purity > 93%. Purified mast cells were precultured with stem cell factor (SCF) (10 ng/ml) and myeloma IgE (3 micrograms/ml) for 16 h before challenge with anti-IgE (1 or 10 micrograms/ml). IgE-dependent activation of lung mast cells caused expression of IL-5 mRNA, which was evident by 2 h and persisted for up to 48-72 h in all of 12 experiments, whereas IL-4 mRNA expression was of a shorter duration and was demonstrable in 6 of 13 experiments. We confirmed that mast cells, and not T cells, were the source of these cytokine messages by using reverse transcriptase-PCR in cell preparations containing known numbers of mast cells and T cells, in situ hybridization in enriched mast cell preparations, and double in situ hybridization-immunocytochemical staining. IL-5 mRNA expression did not require the pretreatment of cells with SCF, whereas expression of IL-4 mRNA seemed to require both anti-IgE and SCF. The strength of IL-5 mRNA signal was related to anti-IgE concentration. Immunoreactive IL-5 was detectable 8 h after anti-IgE challenge, and 10(6) mast cells generated a mean of 731 +/- 400 pg of IL-5 into the supernatant during 48-h culture, but no IL-4 product was detectable. These findings demonstrate the capacity of human lung mast cells to transcribe IL-4 and IL-5 after IgE-dependent activation and to synthesize and release immunoreactive IL-5.