The Use of a Poisson Regression to Evaluate Antihistamines and Fatal Aircraft Mishaps in Instrument Meteorological Conditions.

BACKGROUND: Research indicates that first-generation antihistamine usage may impair pilot performance by increasing the likelihood of vestibular illusions, spatial disorientation, and/or cognitive impairment. Second- and third-generation antihistamines generally have fewer impairing side effects and are approved for pilot use. We hypothesized that toxicological findings positive for second- and third-generation antihistamines are less likely to be associated with pilots involved in fatal mishaps than first-generation antihistamines. METHODS: The evaluated population consisted of 1475 U.S. civil pilots fatally injured between September 30, 2008, and October 1, 2014. Mishap factors evaluated included year, weather conditions, airman rating, recent airman flight time, quarter of year, and time of day. Due to the low prevalence of positive antihistamine findings, a count-based model was selected, which can account for rare outcomes. RESULTS: The means and variances were close for both regression models supporting the assumption that the data follow a Poisson distribution; first-generation antihistamine mishap airmen (N = 582, M = 0.17, S2 = 0.17) with second- and third-generation antihistamine mishap airmen (N = 116, M = 0.20, S2 = 0.18). The data indicate fewer airmen with second- and third-generation antihistamines than first-generation antihistamines in their system are fatally injured while flying in IMC conditions. DISCUSSION: Whether the lower incidence is a factor of greater usage of first-generation antihistamines versus second- and third-generation antihistamines by the pilot population or fewer deleterious side effects with second- and third-generation antihistamines is unclear. These results engender cautious optimism, but additional research is necessary to determine why these differences exist.Gildea KM, Hileman CR, Rogers P, Salazar GJ, Paskoff LN. The use of a Poisson regression to evaluate antihistamines and fatal aircraft mishaps in instrument meteorological conditions. Aerosp Med Hum Perform. 2018; 89(4):389-395.

Pilots using selective serotonin reuptake inhibitors compared to other fatally injured pilots.

Selective Serotonin Reuptake Inhibitors (SSRI) were a disqualifying medication for U.S. civil pilots before April 5, 2010. After this date, a Federal Aviation Administration policy was created that allowed airmen, on select SSRIs, a pathway to hold a valid medical certificate. The purpose of this study was to provide a detailed look at SSRIs in the U.S. pilot population since the inception of this new policy. We examined the toxicology results from fatally injured airmen in addition to outcomes concerning pilots who are participating in the program. This study examined data from the Civil Aerospace Medical Institute's Bioaeronautical Sciences Research Laboratory in conjunction with the Medical Analysis Tracking Registry and the Document Imaging and Workflow System. A count-based regression model quantified the relationships between positive SSRI findings with additional factors of interest. These factors included pilot rating, ethanol, and first generation antihistamines. There were 1484 fatally injured airmen over the six year study period, of which 44-tested positive for an SSRI. First-generation antihistamines were statistically associated with positive findings of SSRIs.

Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.

PURPOSE: The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. EXPERIMENTAL DESIGN: The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. RESULTS: In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560-0.788), ERG (AUC 0.785 (CI:0.680-0.890), PCA3 (AUC 0.681 (CI:0.567-0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600-0.888), and TMPRSS2 (AUC 0.637 (CI:0.519-0.754). CONCLUSION: This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

Diabetes mellitus in patients with Alzheimer's disease: clinical description and correlation with the APOE genotype in a sample population from the province of Antioquia, Colombia.

INTRODUCTION: Alzheimer's disease is a multifactorial disease affecting approximately twenty million people worldwide. Numerous variables are associated with increased risk of developing this severe neurological disorder. Among the risk factors, diabetes mellitus, and the ε4 isoform of the APOE gene have been amply demonstrated as increasing the risk of developing this disease. OBJECTIVE: To determine if a correlation exists between APOE genotype, diabetes mellitus and Alzheimer's disease. MATERIALS AND METHODS: Clinical studies were carried out by surveying the clinical histories in a group of patients in the province of Antioquia, Colombia. Forty-three Alzheimer's patients were compared with 43 control subjects, paired by age and gender. Commercially available methods were used to determine whether the patients had diabetes, and restriction enzyme-based genotyping was used to determine the APOE genotypes. RESULTS: The most common non-neurological comorbidities were: arterial hypertension, acute myocardial infarction, chronic obstructive pulmonary disease and hypothyroidism. From the many variables investigated, two were conclusive: (1) the presence of Alzheimer's disease was higher in patients with diabetes mellitus, and (2) no correlation between late-onset sporadic Alzheimer's disease and APOE was found in the target population. CONCLUSIONS: To detect any association with the APOE genotype, a study involving much a larger population samples must be undertaken.

Diabetes mellitus in patients withAlzheimer´s disease: clinical descriptionand correlation with the APOEgenotype in a sample population from the province of Antioquia, Colombia / Diabetes mellitus en pacientes con enfermedad de Alzheimer: descripción clínica y correlación con el genotipo APOE en una muestra de población del departamento de Antioquia, Colombia

Introduction. Alzheimer´s disease is a multifactorial disease affecting approximately twenty million people worldwide. Numerous variables are associated with increased risk of developing this severe neurological disorder. Among the risk factors, diabetes mellitus, and the ε4 isoform of the APOE gene have been amply demonstrated as increasing the risk of developing this disease. Objective. To determine if a correlation exists between APOE genotype, diabetes mellitus and Alzheimer´s disease. Materials and methods. Clinical studies were carried out by surveying the clinical histories in a group of patients in the province of Antioquia, Colombia. Forty-three Alzheimer´s patients were compared with 43 control subjects, paired by age and gender. Commercially available methods were used to determine whether the patients had diabetes, and restriction enzyme-based genotyping was used to determine the APOE genotypes. Results. The most common non-neurological comorbidities were: arterial hypertension, acute myocardial infarction, chronic obstructive pulmonary disease and hypothyroidism. From the many variables investigated, two were conclusive: (1) the presence of Alzheimer´s disease was higher in patients with diabetes mellitus, and (2) no correlation between late-onset sporadic Alzheimer´s disease and APOE was found in the target population. Conclusions. To detect any association with the APOE genotype, a study involving much a larger population samples must be undertaken.

Introducción. La enfermedad de Alzheimer es compleja y afecta, aproximadamente, a 20 millones de personas en todo el mundo. Muchas variables parecen aumentar el riesgo de desarrollar esta alteración neurológica. Entre los factores de riesgo, se ha demostrado ampliamente que la diabetes mellitus y la isoforma ε4 del gen APOE tienen incidencia positiva en el desarrollo de la enfermedad. Se reporta un estudio en el cual se investigó la posible correlación entre APOE, diabetes mellitus y la enfermedad de Alzheimer, en un grupo específico de pacientes del departamento de Antioquia, Colombia. Objetivo. Determinar si existe una correlación entre APOE, diabetes mellitus y la enfermedad de Alzheimer, en un grupo de pacientes de Antioquia, Colombia. Materiales y métodos. Se buscaron y analizaron las historias clínicas de los pacientes con diagnóstico de enfermedad de Alzheimer. Se seleccionaron aquellos que cumplían los criterios de inclusión. Se utilizaron métodos comercialmente disponibles para confirmar la presencia de diabetes mellitus. La genotipificación de APOE se hizo con un método basado en la PCR y la digestión con enzimas de restricción, en muestras de todos los participantes en el estudio. Resultados. En este estudio se analizan 43 casos de enfermedad de Alzheimer y 43 individuos sanos controles, pareados por edad y sexo. Las enfermedades concomitantes no neurológicas más comunes fueron: hipertensión arterial, infarto agudo del miocardio, enfermedad pulmonar obstructiva crónica e hipotiroidismo. Conclusiones. De las diferentes variables investigadas, dos arrojaron resultados concluyentes: i) la presencia de la enfermedad de Alzheimer es más frecuente en pacientes con diabetes mellitus, y 2) no se encontró correlación entre la enfermedad de Alzheimer de inicio tardío esporádico y el genotipo de APOE. Es importante indicar que debe llevarse a cabo un estudio con un tamaño de población mayor, para determinar cualquier posible correlación o inferencia con el genotipo de APOE.

[Adverse reactions to mosquito bites in scholars from Monterrey, Nuevo Leon, Mexico]. / Reacciones adversas a las picaduras de mosquito en niños escolares de Monterrey, Nuevo León.

BACKGROUND: Allergic reactions to insect bites are a global problem, the true incidence and prevalence of morbidity from adverse reactions to mosquito bites are unknown. OBJECTIVE: To describe the adverse reactions to mosquito bites in school-age children of Monterrey, Nuevo Leon. MATERIAL AND METHODS: A cross-sectional descriptive study was made via a randomized application of questionnaires to children from public elementary schools in the metropolitan area of Monterrey, Nuevo Leon. RESULTS: A total of 11 public schools randomly selected were included in the study. One thousand questionnaires were submitted, of which 506 fulfilled the inclusion criteria; 55% were females. Seventy-six percent referred adverse reactions to mosquito bites, itching (75%) and rash (72%) being the most frequent ones, in the last 12 months. CONCLUSIONS: Adverse reactions to mosquito bites occur frequently. Early detection is important to establish a prompt treatment.

New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction.

BACKGROUND: Despite increasing evidence for the presence of voltage-gated Na(+) channels (Na(v)) isoforms and measurements of Na(v) channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Na(v) channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Na(v) channels in the control of rat aortic contraction. METHODOLOGY/PRINCIPAL FINDINGS: Na(v) channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na(v) channels and smooth muscle alpha-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Na(v) transcripts: Na(v)1.2, Na(v)1.3, and Na(v)1.5. Only the Na(v)1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Na(v) channel agonist veratridine and antagonist tetrodotoxin (TTX), we unmasked a contribution of these channels in the response to the depolarizing agent KCl on rat aortic isometric tension recorded from endothelium-denuded aortic rings. Experimental conditions excluded a contribution of Na(v) channels from the perivascular sympathetic nerve terminals. Addition of low concentrations of KCl (2-10 mM), which induced moderate membrane depolarization (e.g., from -55.9+/-1.4 mV to -45.9+/-1.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 microM) and blocked by TTX (1 microM). KB-R7943, an inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX. CONCLUSIONS/SIGNIFICANCE: These results define a new role for Na(v) channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.

ATP/UTP activate cation-permeable channels with TRPC3/7 properties in rat cardiomyocytes.

Extracellular purines and pyrimidines have major effects on cardiac rhythm and contraction. ATP/UTP are released during various physiopathological conditions, such as ischemia, and despite degradation by ectonucleotidases, their interstitial concentrations can markedly increase, a fact that is clearly associated with arrhythmia. In the present whole cell patch-clamp analysis on ventricular cardiomyocytes isolated from various mammalian species, ATP and UTP elicited a sustained, nonselective cationic current, I(ATP). UDP was ineffective, whereas 2'(3')-O-(4-benzoylbenzoyl)-ATP was active, suggesting that P2Y(2) receptors are involved. I(ATP) resulted from the binding of ATP(4-) to P2Y(2) purinoceptors. I(ATP) was maintained after ATP removal in the presence of guanosine 5'-[gamma-thio]triphosphate and was inhibited by U-73122, a PLC inhibitor. Single-channel openings are rather infrequent under basal conditions. ATP markedly increased opening probability, an effect prevented by U-73122. Two main conductance levels of 14 and 23 pS were easily distinguished. Similarly, in fura-2-loaded cardiomyocytes, Mn(2+) quenching and Ba(2+) influx were significant only in the presence of ATP or UTP. Adult rat ventricular cardiomyocytes expressed transient receptor potential channel TRPC1, -3, -4, and -7 mRNA and the TRPC3 and TRPC7 proteins that coimmunoprecipitated. Finally, the anti-TRPC3 antibody added to the patch pipette solution inhibited I(ATP). In conclusion, activation of P2Y(2) receptors, via a G protein and stimulation of PLCbeta, induces the opening of heteromeric TRPC3/7 channels, leading to a sustained, nonspecific cationic current. Such a depolarizing current could induce cell automaticity and trigger the arrhythmic events during an early infarct when ATP/UTP release occurs. These results emphasize a new, potentially deleterious role of TRPC channel activation.

Tomaculous neuropathy in an airline pilot.

Tomaculous neuropathy is an infrequently reported cause of peripheral neuropathy. It typically represents an inherited condition, although de novo chromosomal mutations have been reported. The condition may be easily confused with other sensorineural neuropathies unless a high degree of suspicion is maintained and a thorough clinical evaluation is performed. The condition is likely under-diagnosed and underreported because of its episodic, transient nature and the extensive differential diagnoses. This condition rarely leads to significant physical incapacitation; however, as evidenced in this case, the degree of limitation could lead to transient occupational incapacitation with definite implications for aeromedical certification.

Causas de muerte en pacientes mentales del Hospital Psiquiátrico de La Habana: estudio comparativo / Causes of death in mental patients of the psychiatric hospital of Havana: a Comparative study

Existe una elevada mortalidad en enfermos mentales en comparación con la población mentalmente enferma, bien por factores inherentes a la enfermedad mental o al uso de diversos fármacos en el tratamiento de la misma. Clasificar las causas de muerte en los pacientes mentales y compararlas con el material necrópsico de un hospital general relacionando su causalidad con la propia enfermedad mental o con los tratamientos psicofarmacológicos. Se analizaron los protocolos de necropsias realizadas entre el día 1ro de enero de 1971 y el 31 de diciembre del 2006 correspondientes a 2,363 pacientes esquizofrénicos y 830 pacientes no esquizofrénicos para un total de 3,193 enfermos mentales fallecidos en el Hospital Psiquiátrico de la Habana (H.P.H.) y se compararon los resultados con el material necrópsico integrado por las necropsias de 1,000 pacientes fallecidos en el hospital docente “Dr. Joaquín Albarrán”, utilizándose la Clasificación Internacional de Enfermedades (CIE-IO) abreviada. En la población mentalmente enferma, la primera causa de muerte correspondió a las enfermedades cardiovasculares, con escasa diferencia entre esquizofrénicos y no esquizofrénicos, 38,68 por ciento y 41,45 por ciento respectivamente mientras en los pacientes de la población general la proporción llegó al 50.10 por ciento, siendo notoria la diferencia en enfermedades neurovasculares con sólo el 2,79 por ciento y 3,01por ciento en el H.P.H. contra el 8,30 por ciento en el “Albarrán”, existiendo variabilidad en el resto de las causas de muerte. Conclusiones: Existen diferencias cualitativas y cuantitativas para todas las causas de muerte en ambos grupos.

There is a high mortality in mental patients in comparison to the mentally sick population on account to inherent factors of the mental illness or to the use of diverse medications in its treatment. To classify the causes of death in mental patients and compare them with the necropsy material of a general hospital relating their causality with the mental disease or with psychopharmacologic treatment. The protocols of necropsies done since January 1st, 1971 to December 31st, 2006 of 2,363 schizophrenic patients and 830 non schizophrenic patients for a total of 3,193 mental patients diseased at the Psychiatric Hospital of Havana were analyzed and were compared with the results of the necropsy material set up by the necropsies of 1,000 patients diseased at “Dr.Joaquín Albarrán” Teaching Hospital using the International Classification of Disease (CIE-IO). On mentally sick population, the first cause of death was related to cardiovascular diseases, with an irrelevant different between schizophrenic and non schizophrenic patients, 38, 68 per cent and 41, 45 per cent respectively meanwhile on patients of the general population the proportion was 50.10 per cent being relevant the difference on neurovascular diseases only with 2, 79 per cent and 3, 01per cent at the Psychiatric Hospital of Havana versus 8, 30 per cent at “Dr. Joaquin Albarrán” Hospital remaining a variability in the other causes of death. There are qualitative and quantitative differences for all the causes of death on both groups.

Causas de muerte en pacientes mentales del Hospital Psiquiátrico de La Habana: estudio comparativo / Causes of death in mental patients of the psychiatric hospital of Havana: a Comparative study

Existe una elevada mortalidad en enfermos mentales en comparación con la población mentalmente enferma, bien por factores inherentes a la enfermedad mental o al uso de diversos fármacos en el tratamiento de la misma. Clasificar las causas de muerte en los pacientes mentales y compararlas con el material necrópsico de un hospital general relacionando su causalidad con la propia enfermedad mental o con los tratamientos psicofarmacológicos. Se analizaron los protocolos de necropsias realizadas entre el día 1ro de enero de 1971 y el 31 de diciembre del 2006 correspondientes a 2,363 pacientes esquizofrénicos y 830 pacientes no esquizofrénicos para un total de 3,193 enfermos mentales fallecidos en el Hospital Psiquiátrico de la Habana (H.P.H.) y se compararon los resultados con el material necrópsico integrado por las necropsias de 1,000 pacientes fallecidos en el hospital docente “Dr. Joaquín Albarrán”, utilizándose la Clasificación Internacional de Enfermedades (CIE-IO) abreviada. En la población mentalmente enferma, la primera causa de muerte correspondió a las enfermedades cardiovasculares, con escasa diferencia entre esquizofrénicos y no esquizofrénicos, 38,68 por ciento y 41,45 por ciento respectivamente mientras en los pacientes de la población general la proporción llegó al 50.10 por ciento, siendo notoria la diferencia en enfermedades neurovasculares con sólo el 2,79 por ciento y 3,01por ciento en el H.P.H. contra el 8,30 por ciento en el “Albarrán”, existiendo variabilidad en el resto de las causas de muerte. Conclusiones: Existen diferencias cualitativas y cuantitativas para todas las causas de muerte en ambos grupos(AU)

There is a high mortality in mental patients in comparison to the mentally sick population on account to inherent factors of the mental illness or to the use of diverse medications in its treatment. To classify the causes of death in mental patients and compare them with the necropsy material of a general hospital relating their causality with the mental disease or with psychopharmacologic treatment. The protocols of necropsies done since January 1st, 1971 to December 31st, 2006 of 2,363 schizophrenic patients and 830 non schizophrenic patients for a total of 3,193 mental patients diseased at the Psychiatric Hospital of Havana were analyzed and were compared with the results of the necropsy material set up by the necropsies of 1,000 patients diseased at “Dr.Joaquín Albarrán” Teaching Hospital using the International Classification of Disease (CIE-IO). On mentally sick population, the first cause of death was related to cardiovascular diseases, with an irrelevant different between schizophrenic and non schizophrenic patients, 38, 68 per cent and 41, 45 per cent respectively meanwhile on patients of the general population the proportion was 50.10 per cent being relevant the difference on neurovascular diseases only with 2, 79 per cent and 3, 01per cent at the Psychiatric Hospital of Havana versus 8, 30 per cent at “Dr. Joaquin Albarrán” Hospital remaining a variability in the other causes of death. There are qualitative and quantitative differences for all the causes of death on both groups(AU)

Pilot medical history and medications found in post mortem specimens from aviation accidents.

INTRODUCTION: Federal Aviation Administration (FAA) regulations require pilots to report all medications and medical conditions for review and consideration as to the overall suitability of the pilot for flight activities. METHODS: Specimens were collected by local pathologists from aviation accidents and sent to the Bioaeronautical Sciences Research Laboratory for analysis. The results of such tests were entered into the Forensic Case Management System. This database was searched to identify all pilots found positive for medications used to treat cardiovascular, psychological, or neurological conditions over the period January 1, 1993, through December 31, 2003. RESULTS: Toxicological evaluations were performed on 4143 pilots. Psychotropic drugs were found in 223 pilots. Cardiovascular medications were found in 149 pilots. Neurological medications were found in 15 pilots. Pilots reported psychological conditions in 14 of the 223 pilots found positive for psychotropic drugs. Only 1 of the 14 pilots reporting a psychological condition to the FAA reported the psychotropic medication found after the accident. Cardiovascular disease was reported by 69 of the pilots found with cardiovascular drugs in their system. Cardiovascular medications found in the pilots were reported by 29 of the 69 pilots reporting a cardiovascular condition. Only 1 of the 15 pilots reported having a neurological condition to the FAA; none of the pilots found with neurological medications reported the medication. CONCLUSIONS: Toxicology successfully identified 93% of the medications reported by the pilots. Pilots involved in fatal accidents taking psychotropic or neurological medications rarely reported the medication or their underlying medical condition to the FAA.

Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice.

OBJECTIVE: Beta-adrenergic stimulation modulates cardiac contractility through protein kinase A (PKA), which phosphorylates proteins such as troponin I (cTnI) and C-protein (cMyBP-C). The relative contributions of cTnI and cMyBP-C to the regulation of myofilament Ca(2+) sensitivity are still controversial because of difficulty in targeting specific protein phosphorylation. Recently, impaired relaxation was found in cMyBP-C-deficient mice (KO) in vivo under basal conditions and after beta-adrenergic stimulation. The goal of this study was to analyse the length-dependent and PKA-dependent modulations of the cardiac contractile machinery in a mouse model lacking cMyBP-C. METHODS: In the present work, we studied the PKA effect on myofilament Ca(2+) sensitivity of left ventricular skinned myocytes isolated from 5-week- and 55-week-old wild-type (WT) and cMyBP-C knockout (KO) mice at 1.9 and 2.3 mum sarcomere lengths (SL). The cTnI content and phosphorylation status were examined by Western blot analysis. RESULTS: Without PKA stimulation and at the shorter SL, Ca(2+) sensitivity was higher in KO compared to WT. The difference disappeared at the longer SL. No difference in passive tension or maximal active tension was observed. PKA stimulation induced a desensitization of WT myofilaments at both SL but had almost no effect in KO myofilaments despite similar levels of cTnI phosphorylation. We also observed expression of slow skeletal TnI in KO animals that was not correlated with the PKA effects. CONCLUSION: The results suggest that cMyBP-C contributes to the regulation of cardiac contraction at short sarcomere length and that myofilament desensitization induced by PKA requires the presence of cMyBP-C and does not depend only upon TnI phosphorylation.