Mutational status of PIK3ca oncogene in oral cancer-In the new age of PI3K inhibitors.

In the new age of PI3K inhibitors, the mutational status of PI3Kca oncogene in the Cavity Squamous Cell Carcinoma (OC-SCC) needs further analysis. It is the sixth most common cancer in the world. The aim of this study was to evaluate PI3Kca oncogene mutations and to correlate them with the clinical-histological characteristics of individuals presenting these tumors. We recruited 74 individuals with OC-SCC diagnosis (period 2000-2014). Histological sections were used. DNA was purified; PIK3ca gene exons 9 and 20 were amplified and sequenced. In 49/74 cases (66 %), the complete sequence of both codons was analyzed by Sanger method. We found that 7/49 (14 %) individuals mutated. In exon 9 we found 1/49 (2 %), and in exon 20 M1043I 8/49 (16 %). We have found the coexistence of more than one mutation in a same individual (E542 K and M1043I). A positive association was observed between the mutational status of the codon 9 (E542 K) and the tongue location. In conclusion, the frequency of PI3Kca gene mutation in OC-SCC was 16 %, which is similar to that reported for other populations. We found a mutation not previously described (M1043I) in this pathology. Should its biological effect be confirmed, it must be added to the list of PIK3ca mutations. Total mutations in the PIK3ca were 32 %, with tongue being the site at the greatest risk (E542K-E545K-M1043I). These findings would facilitate the identification of patients with therapeutic targets in the near future.

Comparison of dung beetle communities (Coleoptera: Scarabaeidae: Scarabaeinae) in oil palm plantations and native forest in the eastern Amazon, Brazil

Abstract In order to evaluate the impact of oil palm cultivation on dung beetles in the eastern Brazilian Amazon, comparisons were made of communities in oil palm plantations and native forest. Pitfall traps baited with human feces were buried to soil level in plantations and surrounding forests. Fifty traps were used in each type of vegetation, placed at 50 m intervals along five transects. Dung beetle communities in oil palm plantations have lower species richness (18 spp.) than in surrounding tropical rainforest (48 spp.), as well as altered species composition. Total abundance of individuals was not significantly different between the two habitats, but species composition was greatly different. Species evenness was greater in the forest. Forest corridors for the preservation of dung beetle species may need to be much wider than current designs. The erosion of biodiversity in dung beetles due to oil palm monoculture parallels what has been seen in other animal taxa in tropical tree plantations.

Peanut avoidance and peanut allergy diagnosis in siblings of peanut allergic children.

BACKGROUND: Studies suggest that siblings of children with peanut allergy (PNA) have a higher prevalence of PNA than the general population. OBJECTIVES: The Canadian Peanut Allergy Registry was used to assess the percentage of siblings of registered index PNA children who were 1) never exposed to peanut or 2) reportedly diagnosed with PNA by a physician without either a history of allergic reaction or a confirmatory testing. Sociodemographic and clinical factors that may be associated with either outcome were evaluated. METHODS: Parents completed a questionnaire on siblings' sociodemographic characteristics, exposure and reaction to peanut, confirmatory tests performed and whether PNA had been diagnosed. RESULTS: Of 932 Registry families, 748 families responded, representing 922 siblings. 13.6% of siblings had never been exposed to peanut, 70.4% (n = 88) of which were born after the index child. Almost 9% of siblings (80) were reported as PNA, but almost half of this group had no history of an allergic reaction to peanut, including five children who also had no testing to confirm PNA. Of these 5, 4 were born after PNA diagnosis in the index child. In a multivariate regression analysis for siblings at least 3 years old, those born after PNA diagnosis in the index child were more likely to have never been exposed to peanut. In a univariate analysis, siblings born after the diagnosis of PNA in the index child were more likely to be diagnosed with PNA without supportive history or confirmatory testing. CONCLUSIONS AND CLINICAL RELEVANCE: These data estimate that more than 10% of siblings of PNA patients will avoid peanut and that siblings born after the diagnosis of PNA in an index child are more likely to have never been exposed. Educational programs and guidelines that caution against unnecessary avoidance are required.

Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.

Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.

Expresión inmunohistoquímica de p53 en individuos con liquen / Immunohistochemical expression of p53 in individuals with lichen planus

Objetivo: Estimar el riesgo del potencial de malignización del liquen plano bucal analizando la expresión de la proteína p53. Materiales y metodos: Se realizó un diseño de cohorte de sujetos con diagnostico histopatológico de liquen. El desenlace fue el desarrollo de cáncer si/no. El total de individuos que cumplió con los criterios de inclusión/exclusión fue de 58. A los 58 sujetos se les realizó la determinación de p53. Resultados: Cuarenta y nueve individuos mostraron una expresión de p53 menor al 5% con una P>0,05% intrasujeto no transformado. En los 9 individuos transformados se observaron diferencias significativas entre la determinación pre y post de la proteína p53. El Riesgo Relativo fue de 188 con una significación estadística de P< 0,01. Conclusion: La expresión de la proteína p53 en los individuos con liquen apoya la hipótesis que niveles superiores al 5%constituye un factor de incremento del riesgo en la transformación maligna de esta patología. Nuestros hallazgos deberían ser corroborados en el futuro con mayor número de individuos. La determinación de la p53 mediante IHQ en individuos con liquen plano bucal podría modificar el seguimiento clínico de estos individuos. Esto permitiría un diagnóstico precoz de cualquier alteración que pueda indicar un posible cambio hacia la malignización.

Objective: To determine the risk for potential malignant transformation of oral lichen planus by analyzing protein p53 expression. Materials and methods: Cohort study of subjects with a histopathologic diagnosis of lichen. The study analyzed whether or not subjects developed cancer. A total of 58 subjects fulfilled the inclusion/exclusion criteria, and were analyzed for p53. Results: Fortynine(49) subjects showed a p53 expression <5%, with a p>0.05 among subjects undergoing no transformation. In the 9 subjects undergoing malignant transformation, significant differences were observed between pre and post p53 expression. The relative risk was 188, with a statistical significance of p< 0.01. Conclusions: Protein p53 expression in subjects with lichen supports the hypothesis that levels >5% are associated with an increased risk of malignant transformation of this condition. Should our findings be proved in a larger series in the future, the clinical follow-up of these subjects could be modified. This would allow an early diagnosis of any disorder indicative of a potential malignant transformation.

A majority of parents of children with peanut allergy fear using the epinephrine auto-injector.

Prompt epinephrine administration is crucial in managing anaphylaxis, but epinephrine auto-injectors (EAIs) are underutilized by patients and their families. Children with peanut allergy were recruited from the Allergy Clinics at the Montreal Children's Hospital, food allergy advocacy organizations and organizations providing products to allergic individuals. Parents of children who had been prescribed an EAI were queried on whether they were fearful of using it and on factors that may contribute to fear. A majority of parents (672/1209 = 56%) expressed fear regarding the use of the EAI. Parents attributed the fear to hurting the child, using the EAI incorrectly or a bad outcome. Parents whose child had longer disease duration or a severe reaction and parents who were satisfied with the EAI training or found it easy to use were less likely to be afraid. Families may benefit from simulation training and more education on the recognition and management of anaphylaxis.

Association of postalimentary lipemia with atherosclerotic manifestations

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Association of postalimentary lipemia with atherosclerotic manifestations.

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Comparing school environments with and without legislation for the prevention and management of anaphylaxis.

BACKGROUND: School personnel in contact with students with life-threatening allergies often lack necessary supports, creating a potentially dangerous situation. Sabrina's Law, the first legislation in the world designed to protect such children, requires all Ontario public schools to have a plan to protect children at risk. Although it has captured international attention, the differences a legislative approach makes have not been identified. Our study compared the approaches to anaphylaxis prevention and management in schools with and without legislation. METHODS: Legislated (Ontario) and nonlegislated (Alberta, British Columbia, Newfoundland and Labrador, and Quebec) environments were compared. School board anaphylaxis policies were assessed for consistency with Canadian anaphylaxis guidelines. Parents of at-risk children and school personnel were surveyed to determine their perspectives on school practices. School personnel's EpiPen5 technique was assessed. RESULTS: Consistency of school board policies with anaphylaxis guidelines was significantly better in a legislated environment (P=0.009). Parents in a legislated environment reported more comprehensive anaphylaxis emergency forms (P<0.001), while school personnel in nonlegislated environments reported more comprehensive forms (P=0.004). Despite school personnel in both environments receiving EpiPen5 training (>80%), suboptimal technique was commonly observed. However, school personnel in the legislated environment had better technique (P<0.001). CONCLUSION: Our results suggest that school boards in legislated environments have made greater efforts to support students at risk for anaphylaxis compared to nonlegislated environments. However, significant gaps exist in both environments, especially with respect to EpiPen5 administration, content, and distribution of anaphylaxis emergency forms, and awareness of school procedures by school personnel and parents.

Gaps in anaphylaxis management at the level of physicians, patients, and the community: a systematic review of the literature.

Diagnosis and management of anaphylaxis can be a challenge because reactions are often unexpected and progress quickly. The focus of anaphylaxis management has mostly been on the acute episode, with little attention given to the long-term management of patients at risk. This is compounded by conflicting information in current guidelines and a general lack of agreement among clinicians about which management strategies are the most appropriate. We systematically reviewed the literature to identify and summarize studies that investigated gaps in anaphylaxis management. Our search included MEDLINE, EMBASE, CINAHL, and Evidence-Based Medicine Reviews. Studies were included if they addressed an outcome describing gaps in anaphylaxis knowledge, education, anaphylaxis management, and quality of life (QOL). Populations of interest were health care professionals involved in the care of patients at risk for anaphylaxis, and patients of any age, their parents, caregivers, and teachers in primary care, hospital or community settings. Of 5014 citations that were identified, the final 59 studies (selected from 75 full-text articles) met the inclusion criteria. Two hundred and two gaps were identified and classified according to major themes: gaps in knowledge and anaphylaxis management (physicians and patients); gaps in follow-up care (physicians); and QOL of patients and caregivers. Findings from this systematic review revealed gaps in anaphylaxis management at the level of physicians, patients, and the community. Findings will be used to provide a basis for developing interventional strategies to help address these deficiencies.

The rise of the plasma lipid concentration elicited by dietary sodium chloride restriction in Wistar rats is due to an impairment of the plasma triacylglycerol removal rate.

Studies in humans have indicated that dietary salt restriction raises plasma levels of total cholesterol (TC) and triacylglycerols (TAG). In order to explain the mechanisms involved, a rat experimental model was developed consisting of chronic feeding ad libitum isocaloric diets with variable sodium chloride contents. Rates of synthesis of plasma TAG were measured either as the increase of plasma TAG after blocking its removal from plasma by the intra-arterial pulse infusion of Triton-WR 1339, or as the plasma rate of incorporation of [(14)C]-oleic acid [(14)C]-TAG. Plasma TAG removal rate was determined by the intra-arterial pulse infusion of a lipid emulsion. Severe salt restriction increased the plasma concentrations of TAG (71%) and of TC (10%). This result was not due to modification of the rate of synthesis of plasma TAG but was attributed to a 55% slower rate of removal of the TAG-containing lipoproteins. An increased plasma non-esterified fatty acid concentration, probably due to a salt restriction-related insulin resistance, may have impaired the activity of the enzyme lipoprotein lipase.

Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice.

Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels, including high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the very-low-density lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005), whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL) was observed (P <.02). CETP activity was measured as the transfer of (14)C-cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared with their controls, while in hypothyroid Tg mice plasma CETP activity did not change. The role of CETP in determining the changes in LP profile of hyperthyroid animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid mice exhibited the same percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P <.05). (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR) was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined in 10 tissue samples: levels were significantly increased in skeletal muscle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL activity. Hypothyroid status did not change CETP activity and HDL metabolism.

Plasma lipases and lipid transfer proteins increase phospholipid but not free cholesterol transfer from lipid emulsion to high density lipoproteins.

BACKGROUND: Plasma lipases and lipid transfer proteins are involved in the generation and speciation of high density lipoproteins. In this study we have examined the influence of plasma lipases and lipid transfer protein activities on the transfer of free cholesterol (FC) and phospholipids (PL) from lipid emulsion to human, rat and mouse lipoproteins. The effect of the lipases was verified by incubation of labeled (3H-FC,14C-PL) triglyceride rich emulsion with human plasma (control, post-heparin and post-heparin plus lipase inhibitor), rat plasma (control and post-heparin) and by the injection of the labeled lipid emulsion into control and heparinized functionally hepatectomized rats. RESULTS: In vitro, the lipase enriched plasma stimulated significantly the transfer of 14C-PL from emulsion to high density lipoprotein (p<0.001) but did not modify the transfer of 3H-FC. In hepatectomized rats, heparin stimulation of intravascular lipolysis increased the plasma removal of 14C-PL and the amount of 14C-PL found in the low density lipoprotein density fraction but not in the high density lipoprotein density fraction. The in vitro and in vivo experiments showed that free cholesterol and phospholipids were transferred from lipid emulsion to plasma lipoproteins independently from each other. The incubation of human plasma, control and control plus monoclonal antibody anti-cholesteryl ester transfer protein (CETP), with 14C-PL emulsion showed that CETP increases 14C-PL transfer to human HDL, since its partial inhibition by the anti-CETP antibody reduced significantly the 14C-PL transfer (p<0.05). However, comparing the nontransgenic (no CETP activity) with the CETP transgenic mouse plasma, no effect of CETP on the 14C-PL distribution in mice lipoproteins was observed. CONCLUSIONS: It is concluded that: 1-intravascular lipases stimulate phospholipid transfer protein mediated phospholipid transfer, but not free cholesterol, from triglyceride rich particles to human high density lipoproteins and rat low density lipoproteins and high density lipoproteins; 2-free cholesterol and phospholipids are transferred from triglyceride rich particles to plasma lipoproteins by distinct mechanisms, and 3 - CETP also contributes to phospholipid transfer activity in human plasma but not in transgenic mice plasma, a species which has high levels of the specific phospholipid transfer protein activity.

Lipoprotein desialylation simultaneously enhances the cell cholesterol uptake and impairs the reverse cholesterol transport system: in vitro evidences utilizing neuraminidase-treated lipoproteins and mouse peritoneal macrophages.

Desialylation of low density lipoprotein (LDL) brings about accumulation of cholesterol in cultured cells. The influence of the neuraminidase-treated lipoprotein (LP) on the reverse cholesterol transport system was investigated in vitro utilizing very low density lipoprotein (VLDL), LDL, total high density lipoprotein (HDL) and its subfractions, HDL2 and HDL3, isolated from healthy donor plasma and mouse peritoneal macrophages. It was found that LP desialylation significantly: (1) decreased the capacity of total HDL and of HDL2, but not of HDL3, to efflux cellular cholesterol; (2) lowered the cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT) without modifying the intrinsic LCAT activity of HDL; (3) increased the cholesteryl ester transfer from HDL to apo B-containing LP mediated by cholesteryl ester transfer protein (CETP); (4) enhanced the uptake by macrophages of cholesterol from HDL and LDL, although the amount of cholesterol taken up by the cells was much greater from the desialylated LDL than from desialylated HDL. Taken together, these in vitro evidences indicate that, in addition to enhancing the cell cholesterol LP uptake, desialylation may contribute to the premature development of atherosclerosis by impairing the reverse cholesterol transport system.

The wearing of hydrophilic contact lenses aboard a commercial jet aircraft: I. Humidity effects on fit.

The increasing use of hydrophilic (soft) lenses in the United States hs prompted interest in the clinical investigation of these lenses under various wearing conditions. Any factor causing lens dehydration during wear may affect lens performance and ultimately cause eye discomfort. The purpose of this study was to evaluate the environmental conditions in the aircraft cabin and to observe any changes in the fit of the hydrophilic lenses that might occur during flight. A "laboratory" for testing was set up aboard a World Airways DC-10 on a scheduled round trip between Oakland, California and Honolulu, Hawaii. A keratometer was used to assess lens fit of seven subjects who were wearing hydrophilic lenses. The efficacy of using a soft lens hydrating solution on the fit of the lens was evaluated, but will also be evaluated in a future paper. Atmospheric pressure, humidity, and temperature measurements were recorded throughout the inflight study. The results showed that a decline in cabin humidity from at least 47% to 11% occurred within 30 min of takeoff. Although previous reports have indicated that there are a number of environmental factors in the aircraft that contribute to eye discomfort for lens wearers, this study indicates that low cabin humidity is possibly the most significant factor.