Healthy Adult Volunteers Research Articles

Comparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strain

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

Cerebellar Asymmetry of Motivational Direction: Anger-Dependent Effects of Cerebellar Transcranial Direct Current Stimulation on Aggression in Healthy Volunteers.

It has recently been theorized that the frontal asymmetry of approach- and avoidance-related motivation is mirrored in the posterolateral cerebellum. Accordingly, left-to-right dominant cerebellar activity is associated with avoidance-related motivation, whereas right-to-left dominant cerebellar activity is associated with approach-related motivation. The aim of this study was to examine the cerebellar asymmetry of motivational direction in approach-related behavior in the context of aggression. In this randomized double-blind sham-controlled crossover study, thirty healthy right-handed adult volunteers received 2mA active or sham left cathodal-right anodal transcranial direct current stimulation (tDCS) to the cerebellum on two separate occasions while engaging in the Point Subtraction Aggression Paradigm (PSAP) task to measure aggressive behavior. Self-reported state anger was assessed before, halfway and immediately after the task, and heart rate and heart rate variability (HRV) were measured during the task. No main effects of tDCS on aggressive behavior, heart rate and HRV were found. Higher state anger before and during the PSAP task was associated with increased aggressive behavior in the active compared to sham tDCS condition. Aggressive behavior was positively correlated with heart rate during active tDCS, while an inverse association was observed during sham tDCS. Results provide support for the cerebellar asymmetry of motivational direction in approach-related behavior and illustrate the importance of affective state-dependency in tDCS-related effects.

The effects of endurance physical exercise with fat-free milk intake as a therapy for metabolic syndrome and/or sarcopenia

Background: Nutrition and exercise are important factors for addressing metabolic syndrome and sarcopenia as they are related to insulin secretion. Proteins, particularly branched-chain amino acids (BCAAs), have insulinotropic effects, while exercise reduces insulin secretion. It is thus important to investigate the effects of protein intake and exercise alone and in combination to determine suitable dietary and exercise therapies for treating metabolic syndrome and sarcopenia. Methods: Eight healthy young adult female volunteers participated in a crossover trial consisting of two 5-day experiments. Days 1 and 2 comprised a body-weight-maintained adjustment period during which the participants consumed control diets (energy, 2,010 kcal; protein, 51.9 g). Days 3 to 5 comprised the treatment period during which the participants consumed experimental diets (energy, 2,010 kcal; protein 82.3 g) containing 402 kcal of fat-free milk, and either performed only normal daily activities (non-Ex) or performed normal daily activities and exercised on a bicycle with an ergometer at a target intensity of about 50% of the maximal oxygen intake, expending 402 kcal of additional energy (Ex). Total urine samples were collected during the daytime (6:45 to 18:45) and nighttime (18:45 to 6:45 the next morning). Fasting blood samples were collected early in the morning before and after the treatment period. Results: Plasma valine, leucine, and BCAA levels were significantly elevated after both the non-Ex and Ex periods. Serum insulin levels were significantly elevated only after the non-Ex period. Urinary C-peptide immunoreactivity excretion levels increased significantly during the non-Ex period, but they decreased significantly during the Ex period. After the Ex period, the serum triglyceride and remnant lipoprotein-cholesterol (RLP-C) levels were significantly decreased. Homeostatic model assessment for insulin resistance (HOMA-IR) and atherosclerosis index (AI) values were slightly, yet significantly, increased after the non-Ex period, but were unchanged after the Ex period. The degree of change (Δ) in the RLP-C level significantly and positively correlated with the Δ HOMA-IR and Δ AI.

Effects of Dual Tasks Including Gum Chewing on Prefrontal Cortex Activity.

The purpose of this study was to examine the effects on prefrontal cortex (PFC) activity of listening to pleasant sounds (PS) while walking, gum chewing (GCh), or performing the dual task of walking and gum chewing at the same time (walking + GCh). A total of 11 healthy adult male volunteers participated in the study (mean age: 29.54±3.37). The block design of the trial consisted of a 30-sec rest, a 60-sec task (target task or control task), and a 30-sec rest. There were three target task conditions: walking, GCh, and the dual task. All of these were performed while listening to PS. The control condition was rest (no exercise) while listening to PS. The outcomes measured and measurements used were PFC activity using two-channel near-infrared spectroscopy and participant self-evaluation of the pleasantness of the experience using the visual analogue scale (VAS). Compared to the control condition, there was significantly greater PFC activation during the GCh and the walking + GCh tasks. Compared to the control condition, GCh and walking + GCh showed significantly greater activation on the VAS measure. In conclusion, listening to PS while GCh or walking + GCh increases PFC activity in the lower central region and induces positive emotional change.

Serum Level Alteration of IL-6, IL-1β, and IFN-γ in Groups of Healthy Adults with Oxidative DNA Damage in Najaf Governorate.

Najaf governorate was recorded as one of the most polluted Iraqi governorates with increased cancer, autoimmune, and abortion cases. Study Groups. A total of 88 adult volunteers from three test groups were divided based on their inhabitance in different geographical regions in Najaf governorate. Group 1 (G1; n, 29) inhabitants of Al-Ansar, Al-Abbaseyeh, and Al-Manathera districts, Group 2 (G2; n, 27) inhabitants of 22 different scattered districts of the governorate, Group 3 (G3; n, 32) inhabitants of Kufa city and center districts in the old Najaf city. According to previous authors' findings, all participants had uranium contamination in their urine and blood samples, and also, they had DNA damage according to the level of urinary 8-OHdG compound. The control group 4 (G4; n, 25) were adult healthy Iraqi volunteers who were residents of the Sulaimaniyah governorate, which has low-level uranium pollution. The present study aims to determine the effect of uranium pollution and DNA damage on the immune system function in terms of estimating the levels of serum interleukin (IL)-6, interferon-gamma (IFN-γ), and IL-1 beta (β). Enzyme-linked immunosorbent assay (ELISA) (Sandwich method technique) was used for estimating the serum cytokines levels in test and control groups. A significant elevation of cytokines levels was reported as compared with the control groups (p ≤ 0.01). The level of IL-6 was 764.64 ± 24.12 pg/ml, 768.87 ± 19.64 pg/ml, and 735.62 ± 18.47 in G1, G2, and G3, respectively. The level of IFN-γ was 264.55 ± 19.17 pg/ml, 259 ± 18.76 pg/ml, and 261.20 ± 12.99 pg/ml for G1, G2, and G3, respectively. The level of IL-1β was 99.85 ± 10.81 pg/ml, 116.8 ± 10.71 pg/ml, and 83 ± 19.24 pg/ml in G1, G2, and G3, respectively. The levels of IL-6, IFN-γ, and IL-1β were 86.5 ± 22.9 pg/ml, 19.4 ± 2.8 pg/ml, and 16.1 ± 3.2 pg/ml in the sera of control (G4). The results showed significant statistical elevation with the corresponding p value cut-off p ≤ 0.01 in IL-6, IFN-γ, and IL-1β in the sera of three test groups as compared with the results of the control group. The change in the proinflammatory cytokines (IL-6, IFN-γ, and IL-1β) levels indicates a persistent inflammatory response in the participants and may reflect immune system impairment as a consequence of exposure to long-term low-dose ionizing radiation.

An Efficient Protocol for Isolation, Purification, and Characterization of Human Erythroid Progenitor Cells from Peripheral Blood Samples of Healthy Adult Volunteers

An Efficient Protocol for Isolation, Purification, and Characterization of Human Erythroid Progenitor Cells from Peripheral Blood Samples of Healthy Adult Volunteers

Modification of velopharyngeal closure pressures during phonation by neuromuscular electrical stimulation in healthy individuals.

Rhinophonia aperta may result from velopharyngeal insufficiency. Neuromuscular electrical stimulation (NMES) has been discussed in the context of muscle strengthening. The aim of this study was to evaluate in healthy subjects whether NMES can change the velopharyngeal closure pattern during phonation and increase muscle strength. Eleven healthy adult volunteers (21-57 years) were included. Pressure profiles were measured by high resolution manometry (HRM): isolated sustained articulation of /a/ over 5 s (protocol 1), isolated NMES applied to soft palate above motor threshold (protocol 2) and combined articulation with NMES (protocol 3). Mean activation pressures (MeanAct), maximum pressures (Max), Area under curve (AUC) and type of velum reactions were compared. A statistical comparison of mean values of protocol 1 versus protocol 3 was carried out using the Wilcoxon signed rank test. Ordinally scaled parameters were analyzed by cross table. MeanAct values measured: 17.15±20.69 mmHg (protocol 1), 34.59±25.75 mmHg (protocol 3) on average, Max: 37.86±49.17 mmHg (protocol 1), 87.24±59.53 mmHg (protocol 3) and AUC: 17.06±20.70 mmHg.s (protocol 1), 33.76±23.81 mmHg.s (protocol 3). Protocol 2 produced velum reactions on 32 occasions. These presented with MeanAct values of 13.58±12.40 mmHg, Max values of 56.14±53.14 mmHg and AUC values of 13.84±12.78 mmHg.s on average. Statistical analysis comparing protocol 1 and 3 showed more positive ranks for MeanAct, Max and AUC. This difference reached statistical significance (p=0.026) for maximum pressure values. NMES in combination with articulation results in a change of the velopharyngeal closure pattern with a pressure increase of around 200% in healthy individuals. This might be of therapeutic benefit for patients with velopharyngeal insufficiency.

Multivariate Analysis of Vocal Fold Vibrations in Normal Speakers Using High-Speed Digital Imaging.

Little is known about the normal variations in vocal fold vibrations. We conducted a prospective study on normal subjects using high-speed digital imaging (HSDI) to elucidate key parameters regarding age/gender-related normal variations. Forty-six healthy adult volunteers were divided into young (aged ≤35 years) male, young female, elderly (aged ≥65 years) male, and elderly female subgroups. HSDI data of sustained phonation of /i/ at a comfortable pitch and loudness were obtained, and vibratory parameters were calculated using the visual-perceptual rating, laryngotopography, digital kymography, and glottal area waveform. Multivariate analysis was then performed on these parameters to clarify the subgroup-specific key parameters. Four key parameters were identified from a total of 83: one from visual perceptual rating and three from laryngotopography. Subgroup analyses showed that posterior-to-anterior longitudinal phase difference (PD) and high fundamental frequency (F0) were specific to young female participants. A low F0 was specific to young male participants. Large anterior-to-posterior longitudinal PD and its left-right difference were specific to elderly male participants. There were no key parameters for elderly female participants. Methods that can assess F0 and longitudinal PD, such as visual-perceptual rating and laryngotopography, were effective in the evaluation of normal vocal fold vibrations and their variations.

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations.

Background: Metabolite profiling of blood by nuclear magnetic resonance (NMR) is invaluable to clinical biomarker discovery. To ensure robustness, biomarkers require validation in large cohorts and across multiple centres. However, collection procedures are known to impact on the stability of biofluids that may, in turn, degrade biomarker signals. We trialled three blood collection tubes with the aim of solving technical challenges due to preanalytical variation in blood metabolite levels that are common in cohort studies. Methods: We first investigated global NMR-based metabolite variability between biobanks, including the large-scale UK Biobank and TwinsUK biobank of the general UK population, and more targeted biobanks derived from multicentre clinical trials relating to inflammatory bowel disease. We then compared the blood metabolome of 12 healthy adult volunteers when collected into either sodium fluoride/potassium oxalate, lithium heparin, or serum blood tubes using different pre-processing parameters. Results: Preanalytical variation in the method of blood collection strongly influences metabolite composition within and between biobanks. This variability can largely be attributed to glucose and lactate. In the healthy control cohort, the fluoride oxalate collection tube prevented fluctuation in glucose and lactate levels for 24 hours at either 4 °C or room temperature (20 °C). Conclusions: Blood collection into a fluoride oxalate collection tube appears to preserve the blood metabolome with delayed processing up to 24 hours at 4 °C. This method may be considered as an alternative when rapid processing is not feasible.

Differences in velopharyngeal pressures during speech sound production in patients with unilateral cleft lip and palate (UCLP) and healthy individuals.

During articulation the velopharynx needs to be opened and closed rapidly and a tight closure is needed. Based on the hypothesis that patients with cleft lip and palate (CLP) produce lower pressures in the velopharynx than healthy individuals, this study compared pressure profiles of the velopharyngeal closure during articulation of different sounds between healthy participants and patients with surgically closed unilateral CLP (UCLP) using high resolution manometry (HRM). Ten healthy adult volunteers (group 1: 20-25.5 years) and ten patients with a non-syndromic surgically reconstructed UCLP (group 2: 19.1-26.9 years) were included in this study. Pressure profiles during the articulation of four sounds (/i:/, /s/, /ʃ/ and /n/) were measured by HRM. Maximum, minimum and average pressures, time intervals as well as detection of a previously described 3-phase-model were compared. Both groups presented with similar pressure curves for each phoneme with regards to the phases described and pressure peaks, but differed in total pressures. An exception was noted for the sound /i:/, where a 3-phase-model could not be seen for most patients with UCLP. Differences in velopharynx pressures of 50% and more were found between the two groups. Maximum and average pressures in the production of the alveolar fricative reached statistical significance. It can be concluded that velopharyngeal pressures of patients with UCLP are not sufficient to eliminate nasal resonance or turbulence during articulation, especially for more complex sounds. These results support a general understanding of hypernasality during speech implying a (relative) velopharyngeal insufficiency.

Stability of Aspartate Transaminase in Blood Specimens Subjected to Various Storage Temperatures and Times Prior to Centrifugation

Aspartate Transaminase (AST) is an enzyme used to diagnose medical problems and found in erythrocytes other than in the heart, liver, skeletal muscles, kidney, and brain. Prolonged serum-clot contact time and the fluctuation in storage temperature are possible reasons for the changes in chemical constituents in serum. The objective of this experimental study was to determine the effect of the storage time (three and six hours) before centrifugation and the storage temperature (4℃ and 28℃) on the stability of AST in blood. Methods: The study sample consisted of fifty-three healthy adult volunteers. Five milliliters of blood samples were collected from each subject and then aliquoted into five Eppendorf tubes. One of the aliquots was centrifuged within 30 minutes of collection, and the AST assay was done to obtain the control (baseline) value. Two of the remaining aliquots were stored at 4℃ while the other two aliquots were stored at room temperature for three hours and six hours, respectively prior to centrifugation. The difference between the baseline AST values and paired values of samples at different times of storage and temperatures was analyzed using the non-parametric Wilcoxon signed-rank test. Results: Significant differences were found in AST level compared to the baseline value when samples were stored at room temperature for three hours (p=0.027) and six hours at room temperature (p=0.011). Conclusions: AST in blood was unstable for at least three hours at room temperature (28℃). At 4℃, AST was stable for up to six hours, and blood samples can be stored at 4℃ for up to six hours for analysis of AST.

Investigation of the Validity and Reliability of Two Smart Bands Selected That Count Steps at Different Walking Speed

Whether activity monitor smart wristbands that have become widespread can accurately estimate the step count while walking is a matter of curiosity. The current study aims to analyze the validity and reliability of step count (SC) estimation at normal walking and fast walking pace under controlled conditions of two selected smart wristbands of the leading wearable device vendors, Xiaomi (Mi4) and Huawei (H4). Twenty healthy adult male and twenty healthy adult female were included in the study and analyzed separately. The mean age of male and female participants was 22.25 and 21.62 years, with BMI values of 24.22 kg/m2 and 21.42 kg/m2, respectively. The above-ground walking protocol consisted of four separate five-minute tests: Normal Walking Test, Normal Walking Retest, Fast Walking Test, and Fast Walking Retest. In the study, the analyses were performed by using activity monitor measurements and criterion measurements (the number of steps determined from video recordings), compatibility of test-retest measurement values, error indicators (MPE and MAPE), Intraclass Correlation Coefficients (ICC), and Bland-Altman limits of agreement. According to the current study results, it was revealed that the MAPE values recorded for Mi4 and H4 smart wristbands for both normal and fast walking pace in male and female participants were <5%, which was deemed excellent. According to all analyses, the H4 device was found to be valid and reliable, but according to ICC and Pearson Correlation analyses, the Mi4 device was not found to be valid and reliable at fast walking pace.

Investigation of the Relationship Between Orientation Discrimination Thresholds, Autistic, and Schizotypal Personality Traits

Imbalances in cortical excitation and inhibition (E-I) have been implicated in both autism spectrum conditions (ASC) and schizophrenia spectrum conditions (SSC). However, most studies investigate these clinical conditions independently, possibly due to the difficulty of obtaining comorbid clinical populations. As such, the current study investigated the relationship between performance in the orientation discrimination task “ODT” as a potential proxy for E-I balance and the autistic (as assessed by Autism Spectrum Quotient “AQ”) and schizotypal personality traits (as assessed by Schizotypal Personality Questionnaire-Brief “SPQ-BR”) in the general population. 87 healthy adult volunteers participated in the study. We found that high autistic personality traits are associated with enhanced performance in the oblique condition of ODT. In contrast, high schizotypal personality traits are associated with poor performance in the vertical condition of ODT. Such associations support the suggested disruption of cortical E-I balance in ASC and SSC.

Comparative Validation Study between Pneumatic Tube System and Hand Carried Blood Sample

Rapid delivery of specimens is crucial in today's clinical laboratories, and pneumatic tube systems are commonly utilized for this purpose. The validation of sample stability through pneumatic tube system (PTS) is essential. The use of Pneumatic Tube System can improve specimen turnaround time; allowing more effective time management of the porters by reducing the need to physically take specimens from one department to another. Prior to use, the Pneumatic tube system must be validated to ensure the reliability of laboratory test results, particularly those impacted by movement, such as lactate dehydrogenase (LDH), aspartate aminotransferase (AST), potassium (K+), complete blood count (CBC), particularly hemoglobin and coagulation tests. The most common way of validating pneumatic tube systems is to compare blood samples transported by pneumatic tube systems to blood samples transported by hand. High speeds and rapid acceleration of blood samples can increase the risk of hemolysis and negatively affect sample quality and test results. Moreover, the installation and design of each pneumatic tube system exhibit unique characteristics that are exclusive to each individual institution. The established protocol necessitated the use of either a human courier or pneumatic tube technology in order to transport a collection of replicated samples to the laboratory. Comparative research will be conducted on a sample size of twenty healthy adult volunteers to assess the integrity of the sample. The main objective of our study was to evaluate the effects of PTS transportation on laboratory results and whether is there any difference as compared to hand courier method.

Finite element analysis and a pilot study of different fixation constructs for Danis-Weber A and B lateral malleolus fractures

BackgroundDisplaced lateral malleolus fractures are typically stabilised through open reduction and internal fixation. The biomechanically and clinically efficacy of locking plates and lag screws, particularly in Weber A and B distal fibular fractures remains a subject of contention. This study examines two locking plate designs for lateral malleolus fractures, evaluating their performance with and without interfragmentary screws using finite element models.MethodsUtilising CT images of a healthy adult male volunteer, a three-dimensional finite element model was constructed. The Fibula-specific Flank Multiaxial Locking Anatomic Plate (FMLP) and the Conventional Locking Plate (CLP) were subjected to stabilisation, both with and without an interfragmentary screw, mimicking the Danis-Weber A and B lateral malleolus oblique fracture fixation. Loads of 140 N and 70 N, equivalent to 20% of the body weight, were applied to simulate the single-leg and two-leg standing conditions in the axial direction. The von Mises stress (VMS) distributions and element displacements were subsequently analyzed.ResultsIn the Danis-Weber A fracture model group, the FMLP with an interfragmentary screw fixation exhibited the lowest peak VMS values: 51.9 MPa in the fibula, 89.0 MPa in the plate, and 61.3 MPa in the screws for simulating single-leg conditions. Under two-leg standing conditions, these peak VMS values decreased to 25.9 MPa in the fibula, 44.5 MPa in the plate, and 30.6 MPa in the screws, respectively. Furthermore, the overall structural peak displacements during single-leg standing for both Weber-A and B fractures with different implants ranged from 1.61 to 2.54 mm. While standing on two feet, the ranged was from 0.80 to 1.27 mm. An interfragmentary screw at the oblique fracture site resulted in reduced the peak value of VMS in the fibula, plate, screws, consequently decreased the overall structural displacement for FMLP and CLP fixation in lateral malleolus fractures.ConclusionsThe current finite element analysis (FEA) demonstrates that FMLP exhibits superior mechanical characteristics in Danis-Weber A and B lateral malleolus fractures compared to CLP. The inclusion of an interfragmentary screw, combined with locking plate design, enhances stability for simple oblique distal fibular fractures. The FMLP presents itself as potential as an alternative for lateral malleolus fractures from a biomechanical perspective. Nevertheless, further verification of these results is imperative through subsequent clinical studies.

Ultrasound evaluation of gastric emptying time of standardized high-calorie liquid meals in healthy adults: A double-blind cross-over randomized study

Commercially available high-calorie drinks containing fat and protein can be used as dietary supplements in surgical patients. According to preoperative fasting guidelines, high-calorie drinks are non-clear fluids and should not be consumed 6h before elective procedures. The aim of this study was to evaluate the gastric emptying time of commercially available high-calorie drink formulations in healthy adults using gastric ultrasound. 25 healthy adult volunteers were included in this double-blind, cross-over prospective study. On three study sessions, fasted volunteers ingested one of the three study products: a solution of 75g of glucose in 200ml of water, a fat-free liquid meal, and a nutritionally complete liquid meal with equal volume and energy content. Gastric ultrasound examinations were performed to evaluate the gastric contents qualitatively and the volume of the gastric contents was calculated from the cross-sectional area of the gastric antrum measured in right lateral position by using a validated model. Repeated gastric ultrasounds were performed at baseline and half-hourly after ingesting the products in supine and right lateral position until the criteria for an empty stomach were met. The glucose solution and the standard fat-free high-calorie drink with the same caloric content had a median gastric emptying time of 150min. The nutritionally complete liquid meal had a median gastric emptying time of 180min. Gastric emptying was complete in all participants before 6h had elapsed since ingesting the study products. High calorie liquid meals have a gastric emptying time longer than the recommended fasting time for clear fluids, but shorter than the recommended fasting time for solids in healthy adults.

The cerebellum during provocation and aggressive behaviour: A 7 T fMRI study

Abstract Increasing empirical evidence points towards the involvement of the cerebellum in anger and aggressive behaviour. However, human functional neuroimaging studies so far have emphasised the involvement of subcortical and cortical regions, rather than examining the contributions of the cerebellum. In the present study, 7 T functional magnetic resonance imaging (fMRI) was used to assess cerebellar activation during provocation and aggressive behaviour elicited by the Point Subtraction Aggression Paradigm in 29 healthy adult volunteers. Provocations resulted in left posterior cerebellar activation, while right posterior cerebellar activation was associated with aggressive behaviour. Our findings confirm the involvement of distinct and lateralised non-motor related cerebellar areas during provocation and aggressive behaviour. This study adds to the growing recognition of the posterior cerebellar regions in emotion- and cognition-dedicated processes and to the role of the little brain in human aggression.

A 13.2 mg epinephrine intranasal spray demonstrates comparable pharmacokinetics, pharmacodynamics, and safety to a 0.3 mg epinephrine autoinjector

BackgroundRecent acute anaphylaxis guideline updates have identified remaining unmet needs based on currently available therapeutic options as a critical focus. ObjectiveThe present study compares the pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of intranasal epinephrine with intramuscular epinephrine administered by autoinjector and manual syringe. MethodsAn open-label, 3-period, crossover study was conducted in 116 healthy adult volunteers to assess the bioavailability of a single intranasal dose of epinephrine, 13.2 mg compared to an intramuscular 0.3 mg autoinjector, and a 0.5 mg manual syringe. Patients achieving epinephrine concentrations of 50, 100, and 200 pg/mL at 10-, 20-, 30-, and 60-minutes post-dose were also evaluated. ResultsPK parameters for the 13.2 mg IN dose exceeded those of the 0.3 mg autoinjector with a rapid and higher Cmax (intranasal, 429.4 pg/mL and autoinjector, 328.6 pg/mL) and greater systemic exposure; AUC0-360 (intranasal=39,060 pg*min/mL, autoinjector=17,440 pg*min/mL). Similar results were observed compared to the 0.5 mg manual syringe. PK parameters for opposite and same nostril dosing were higher than both intramuscular doses, except Tmax, which was bracketed between the 2 intramusculardoses; intranasal opposite and same nostril=20 min, autoinjector=14.9 min, manual syringe=45 min. Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well-tolerated. No serious or unexpected adverse events were reported, confirming results from earlier clinical studies. ConclusionsNDS1C addresses the unmet medical and patient needs for a needle-free, convenient, and effective dose delivery system for self-administration of epinephrine that is as good or better than the 0.3 mg autoinjector.

Flow cytometry for comprehensive assessment of platelet functional activity in response to ADP stimulation.

Flow cytometry with adenosine diphosphate (ADP) allows to characterize molecular changes of platelet function caused by this physiologically important activation, but the methodology has not been thoroughly investigated, standardized and characterized yet. We analyzed the influence of several major variables and chose optimal conditions for platelet function assessment. For activation, 2.5 μM CaCl2 , 5 μM ADP and antibodies were added to diluted blood and incubated for 15 min. We analyzed kinetics of antibody binding and effects of their addition sequence, agonist concentration, blood dilution, exogenous calcium addition and platelet fixation. We tested our protocol on 11 healthy children, 22 healthy adult volunteers, 9 patients after a month on dual antiplatelet therapy after percutaneous coronary intervention (PCI), 7 adult patients and 14 children with immune thrombocytopenia (ITP). We found that our protocol is highly sensitive to ADP stimulation with low percentage of aggregates formation. The assay is also sensitive to platelet function inhibition in post-PCI patients. Finally, platelet preactivation with ITP plasma was stronger and caused increase in activation response to ADP stimulation compared to preactivation with low dose of ADP. Our assay is sensitive to antiplatelet therapy and platelet preactivation in ITP patients under physiological conditions with minimal percentage of aggregates formation.

Effect of direct exposure to ringing mobile phone waves on ECG heart rate and rhythm among healthy adults

The effect of electromagnetic wave from mobile phones on human health is of great interest, the current study was designed to investigate the effect of mobile phone electromagnetic waves on ECG heart rate and rhythm among different healthy adult volunteers’ ages and sex while mobile phone was placed on the chest pocket level during ringing mode. It was an experimental, comparative study conducted in the period from march 2014 to August 2016 in north of Sudan at Elsheikh Abdallah Elbadri University among 850 volunteers, Sudanese and other nationalities.500 male and 350 females, aged 16 - 49 years were included in the study. ECG was done before and after exposure to ringing mobile phone. Significant changes in ECG heart rate and rhythm was detected and the results was found to be consistent in males and females’ group. The study conclude that mobile phone is not a safety device and should not be used by medical staff inside the ECG rooms.