Clinical assessment of tolerability, immunological and cutaneous reactivity effects of an abbreviated schedule with Olea europaeanative extract of subcutaneous immunotherapy.

Summary: Objectives. To evaluate the tolerability and efficacy of Olea europaea subcutaneous immunotherapy (SCIT) on patients with rhinoconjunctivitis. Methods. In this open clinical trial patients were assigned to an abbreviated build-up scheme. The outcomes were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Results. Only 8 systemic reactions were registered, which represented 7/47 (14.9%) of patients and 8/429 (1.9%) of administered doses. Regarding immunological parameters the significant increases of sIgG and sIgG4 evidenced the changes in the patient immune system. Cutaneous reactivity decreased significantly. Conclusions. Olea europaea SCIT (Allergovac® depot ROXALL Medicina España S.A.) showed a good safety and tolerability profile. Immunological changes with induction of blocking IgG and decreases in cutaneous reactivity were detected in the patients.

[A first step towards safer sedation and analgesia: A systematic evaluation of outcomes and level of sedation and analgesia in the mechanically ventilated critically ill patient]. / Un primer paso hacia una analgosedación más segura: evaluación sistemática de objetivos y grado de analgesia y sedación en el paciente crítico con ventilación mecánica.

INTRODUCTION: Safe analgesia and sedation strategies are necessary in order to avoid under or over sedation, as well as improving the comfort and safety of critical care patients. OBJECTIVES: To compare and contrast a multidisciplinary protocol of systematic evaluation and management of analgesia and sedation in a group of critical care patients on mechanical ventilation with the usual procedures. MATERIALS AND METHODS: A cohort study with contemporary series was conducted in a tertiary care medical-surgical ICU February to November during 2013 and 2014. The inclusion criteria were mechanical ventilation ≥ 24h and use of sedation by continuous infusion. Sedation was monitored using the Richmond agitation-sedation scale or bispectral index, and analgesia were measured using the numeric rating scale, or behavioural indicators of pain scale. The study variables included; mechanical ventilation time, weaning time, ventilation support time, artificial airway time, continuous sedative infusion time, daily dose and frequency of analgesic and sedative drug use, hospital stay, and ICU and hospital mortality, Richmond agitation-sedation scale, bispectral index, numeric rating scale, and behavioural indicators of pain scale measurements. Kruskal Wallis and Chi2, and a significance of p<.05 were used. RESULTS: The study included 153 admissions, 75 pre-intervention and 78 post-intervention, with a mean age of 55.7±13 years old, and 67% men. Both groups showed similarities in age, reason for admission, and APACHE. There were non-significant decreases in mechanical ventilation time 4 (1.4-9.2) and 3.2 (1.4-8.1) days, respectively; p= 0.7, continuous sedative infusion time 6 (3-11) and 5 (3-11) days; p= 0.9, length of hospital stay 29 (18-52); 25 (14-41) days; p= 0.1, ICU mortality (8 vs. 5%; p= 0.4), and hospital mortality (10.6 vs. 9.4%: p= 0.8). Daily doses of midazolam and remifentanil decreased 347 (227-479) mg/day; 261 (159-358) mg/day; p= 0.02 and 2175 (1427-3285) mcg/day; 1500 (715-2740) mcg/day; p= 0.02, respectively. There were increases in the use of remifentanil (32% vs. 51%; p= 0.01), dexmedetomidine (0 vs.6%; p= 0.02), dexketoprofen (60 vs. 76%; p= 0.03), and haloperidol (15 vs.28%; p= 0.04). The use of morphine decreased (71 vs. 54%; p= 0.03). There was an increase in the number of measurements and Richmond agitation-sedation scale scores 6 (3-17); 21 (9-39); p< 0.0001, behavioural indicators of pain scale 6 (3-18); 19(8-33); p< 0.001 and numeric rating scale 4 (2-6); 8 (6-17); p< 0.0001. CONCLUSIONS: The implementation of a multidisciplinary protocol of systematic evaluation of analgesia and sedation management achieved an improvement in monitoring and adequacy of dose to patient needs, leading to improved outcomes.

Genetic uniqueness of the Waorani tribe from the Ecuadorian Amazon.

South America and especially the Amazon basin is known to be home to some of the most isolated human groups in the world. Here, we report on a study of mitochondrial DNA (mtDNA) in the Waorani from Ecuador, probably the most warlike human population known to date. Seeking to look in more depth at the characterization of the genetic diversity of this Native American tribe, molecular markers from the X and Y chromosomes were also analyzed. Only three different mtDNA haplotypes were detected among the Waorani sample. One of them, assigned to Native American haplogroup A2, accounted for more than 94% of the total diversity of the maternal gene pool. Our results for sex chromosome molecular markers failed to find close genetic kinship between individuals, further emphasizing the low genetic diversity of the mtDNA. Bearing in mind the results obtained for both the analysis of the mtDNA control region and complete mitochondrial genomes, we suggest the existence of a 'Waorani-specific' mtDNA lineage. According to current knowledge on the phylogeny of haplogroup A2, we propose that this lineage could be designated as subhaplogroup A2s. Its wide predominance among the Waorani people might have been conditioned by severe genetic drift episodes resulting from founding events, long-term isolation and a traditionally small population size most likely associated with the striking ethnography of this Amazonian community. In all, the Waorani constitute a fine example of how genetic imprint may mirror ethnopsychology and sociocultural features in human populations.

Establishing Synoptic Cancer Pathology Reporting in Low- and Middle-Income Countries: A Nicaraguan Experience.

PURPOSE: Cancer pathology reports have traditionally been narrative with limited reliable information. In high-income countries, synoptic format reporting has gradually been introduced to improve patient care and cancer registry input. We posited that introduction of synoptic style reporting was possible in Nicaragua and could serve as a model for other low- and middle-income countries. MATERIALS AND METHODS: The Department of Pathology, Hospital Escuela Oscar Danilo Rosales Argüello (HEODRA), León, Nicaragua, decided to introduce and implement synoptic reporting for all cancer cases beginning in 2018. All 10,012 histopathologic case reports issued by the department from January 1, 2018, through June 30, 2020, were reviewed. After excluding benign lesions, recurrent or metastatic tumors, endometrial biopsies or curettage, and primary cytologic specimens, 724 cases met the criteria for synoptic style reporting. The narrative format, previously used for all cases, was intentionally abandoned. RESULTS: Of the 10,012 reports reviewed at HEODRA during the study period, synoptic-style reporting was used for all 724 cancer cases that met criteria for inclusion in the study. In addition, all elements were listed in the required order. Narrative format of reporting was not used for any of the reports. CONCLUSION: Our experience in Nicaragua has shown that establishing synoptic-style cancer pathology reporting is achievable in a low- or middle-income country. Just as in high-income countries, a dedicated collaborative step-by-step conversion to synoptic reporting can lead to improvement in cancer patient care and quality of data for population-based registries.

SNPSTR rs59186128_D7S820 polymorphism distribution in European Caucasoid, Hispanic, and Afro-American populations.

Single nucleotide polymorphisms (SNPs) in the flanking regions of microsatellite loci (SNPSTRs) help to increase the power of discrimination of short tandem repeat (STR) loci. SNPs are positions in the genome that have been well-conserved over the course of evolution, so analysing them can help distinguish between STR alleles in which the number of repetitions matches due to descent from those which match by chance. This provides support for the determination of biological paternity and other kinship analyses in which mutation needs to be ruled out as grounds for exclusion. Locus D7S820 shows a variable position, SNP rs59186128, in the 5' flanking region. This study is set out (1) to determine the frequencies of SNP rs59186128 in populations with various geographical origins and (2) to estimate the possible contribution of rs59186128 to the allele discrimination of locus D7S820. To that end, individuals from European Caucasoid, Hispanic, and Afro-American populations are studied using denaturing high-performance liquid chromatography, which enables locus rs59186128 to be quickly and highly cost-effectively screened. Moreover, a method is established for determining the haplotypes of SNPSTR rs59186128_D7820. The results show that SNP rs59186128 has a T allele frequency of more than 0.15 in one of the Afro-American populations studied, and the haplotype analysis shows that there is no preferential association between the alleles of SNPSTR rs59186128_D7S820, which supports the idea that they could be useful in forensic applications.

[Prevention of respiratory risks]. / Prevención de riesgos respiratorios.

A need for oxygen is determined by the base pathology a patient suffers which produces immobilization, due to being bedridden and due to the problems which began due to an organic insufficiency associated with muscular weakness, a failure in the respiratory system, insufficient sputum, and cardiovascular alterations. This article deals with those alterations which cause a need to provide oxygen to a patient and its prevention in bedridden patients.

Portfolio Decision Analysis Framework for Value-Focused Ecosystem Management.

Management of natural resources in coastal ecosystems is a complex process that is made more challenging by the need for stakeholders to confront the prospect of sea level rise and a host of other environmental stressors. This situation is especially true for coastal military installations, where resource managers need to balance conflicting objectives of environmental conservation against military mission. The development of restoration plans will necessitate incorporating stakeholder preferences, and will, moreover, require compliance with applicable federal/state laws and regulations. To promote the efficient allocation of scarce resources in space and time, we develop a portfolio decision analytic (PDA) framework that integrates models yielding policy-dependent predictions for changes in land cover and species metapopulations in response to restoration plans, under different climate change scenarios. In a manner that is somewhat analogous to financial portfolios, infrastructure and natural resources are classified as human and natural assets requiring management. The predictions serve as inputs to a Multi Criteria Decision Analysis model (MCDA) that is used to measure the benefits of restoration plans, as well as to construct Pareto frontiers that represent optimal portfolio allocations of restoration actions and resources. Optimal plans allow managers to maintain or increase asset values by contrasting the overall degradation of the habitat and possible increased risk of species decline against the benefits of mission success. The optimal combination of restoration actions that emerge from the PDA framework allows decision-makers to achieve higher environmental benefits, with equal or lower costs, than those achievable by adopting the myopic prescriptions of the MCDA model. The analytic framework presented here is generalizable for the selection of optimal management plans in any ecosystem where human use of the environment conflicts with the needs of threatened and endangered species. The PDA approach demonstrates the advantages of integrated, top-down management, versus bottom-up management approaches.

Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.

Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

Environmental radiation: risk benchmarks or benchmarking risk assessment.

In the wake of the compound March 2011 nuclear disaster at the Fukushima I nuclear power plant in Japan, international public dialogue has repeatedly turned to questions of the accuracy of current risk assessment processes to assess nuclear risks and the adequacy of existing regulatory risk thresholds to protect us from nuclear harm. We confront these issues with an emphasis on learning from the incident in Japan for future US policy discussions. Without delving into a broader philosophical discussion of the general social acceptance of the risk, the relative adequacy of existing US Nuclear Regulatory Commission (NRC) risk thresholds is assessed in comparison with the risk thresholds of federal agencies not currently under heightened public scrutiny. Existing NRC thresholds are found to be among the most conservative in the comparison, suggesting that the agency's current regulatory framework is consistent with larger societal ideals. In turning to risk assessment methodologies, the disaster in Japan does indicate room for growth. Emerging lessons seem to indicate an opportunity to enhance resilience through systemic levels of risk aggregation. Specifically, we believe bringing systemic reasoning to the risk management process requires a framework that (i) is able to represent risk-based knowledge and information about a panoply of threats; (ii) provides a systemic understanding (and representation) of the natural and built environments of interest and their dependencies; and (iii) allows for the rational and coherent valuation of a range of outcome variables of interest, both tangible and intangible. Rather than revisiting the thresholds themselves, we see the goal of future nuclear risk management in adopting and implementing risk assessment techniques that systemically evaluate large-scale socio-technical systems with a view toward enhancing resilience and minimizing the potential for surprise.

GLP-1 effect upon the GPI/IPG system in adipocytes and hepatocytes from diabetic rats.

GLP-1 (glucagon-like peptide 1), proposed as a possible tool for Type 2 diabetes therapy, has insulin-like effects upon glucose metabolism in extrapancreatic tissues, whose plasma membranes contain specific receptors for the peptide, being those, at least in liver and muscle, not associated to the adenylate cyclase/cAMP system. GLP-1, as insulin, modulates the content of glycosylphosphatidylinositols (GPIs)--precursors of inositolphosphoglycans (IPGs), considered mediators of insulin action--in several extrapancreatic cell lines and in normal rat hepatocytes and adipocytes. In the present paper, we document that in a streptozotocin-induced Type 2 diabetic rat model, GLP-1, as insulin, provokes a rapid decrease of the [myo-3H-inositol]GPI content in isolated adipocytes--indicative of its hydrolysis and immediate short-lived generation of IPG--as that previously observed in normal animals; in hepatocytes, GLP-1, but not insulin, induced a reduction in the cellular GPI, although delayed in relation to normal rats. In adipocytes from streptozotocin-induced Type 1 diabetic rats, GLP-1, as insulin, seems to induce a reduction in the cellular GPI content, which was smaller and occurred later than that provoked in the Type 2 diabetic model; in the hepatocytes, GLP-1 and insulin failed to affect the control GPI content at any time tested. In Type 2 diabetic rat, the hepatocyte retains its response capability to GLP-1, but not to insulin, suggesting that the peptide could be bypassing possible defective steps in the insulin signaling pathway in the liver of this diabetic model.

C-kit receptor (CD117) expression in acute leukemia.

The murine monoclonal antibody YB5.B8 (CD117) identifies a transmembrane tyrosine kinase receptor encoded by the human c-kit proto-oncogene. In this study we investigated the expression of c-kit on different types of acute leukemia to determine the degree of specificity and sensitivity of this marker for the myeloid and lymphoid lineages. C-kit was positive in over half of the 115 cases of acute leukemia studied. Overall, two thirds of AML cases expressed c-kit, whereas only one of 23 ALL patients was c-kit positive. C-kit was also positive in 16 of 19 cases of myeloid blast crisis of myeloproliferative disorders and negative in four with a lymphoid phenotype. There was no correlation between c-kit expression and the degree of myeloid differentiation by FAB subtypes or other markers. We conclude that c-kit is a specific marker for the myeloid lineage, which is expressed early during hematopoietic differentiation and can aid the diagnosis of AML in difficult cases. More patients need to be tested to establish whether the expression of c-kit may define AML subgroups of prognostic significance.

[Risk factors for morbidity and mortality in patients with essential hypertension, followed for 25 years]. / Factores predictores de riesgo de morbimortalidad en hipertensos esenciales seguidos 25 años.

BACKGROUND: Among hypertensive patients, other risk factors for mortality and morbidity, besides blood pressure, must be considered when therapeutic decisions are done. AIM: To assess the incidence and relevance of cardiovascular risk factors in a cohort of patients with essential hypertension. MATERIAL AND METHODS: A cohort of 1,072 treated patients with essential hypertension was followed for a period up to 25 years. Four hundred eighty six were men and 586 were women, age ranged from 31 to 70 years. At entry, 56% of subjects did not have any organic complications associated to hypertension (stage I WHO criteria), 30% had mild alterations (Stage II) and 14% had major complications (myocardial infarction, stroke, heart failure or renal failure). Likewise, 43.8% had mild, 14.5%, moderate and 41.7%, severe hypertension. Patients were treated with monotherapy or combined therapy based on diuretics, beta blockers, calcium antagonists and angiotensin converting enzyme inhibitors. Goal of therapy was 140/90 mm Hg. Risk factors associated diseases and complications were registered carefully. Causes of death were obtained from hospital records and death certificates. Mortality was analyzed using life tables (intention to treat method included). RESULTS: Blood pressure dropped significantly during follow up from a mean of 182/110 to 154/92 mm Hg. During follow up, 143 patients died and 429 complications (lethal or non lethal) were recorded. Twenty four percent of patients smoked, 24% reported alcohol intake, 56% had hypercholesterolemia, 11% were obese, 13% had diabetes and 3% had gout. The proportional hazard model showed that the existence of previous complications, the presence of more than 3 risk factors, and age over 60 and mean systolic and diastolic pressure during therapy, were independent and significant risk factors for mortality. CONCLUSIONS: The incidence of risk factors among our hypertensive patients is very similar to that of other national or international cohorts.