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Background: An increasing demand for health care services and getting health care closer to doorsteps of communities has made health managers to use trained community-based health volunteers to support in providing health services to people in rural communities. Community volunteerism in Ghana has been identified as an effective strategy in the implementation of Primary Health Care activities since 1970s. However, little is known about the performance of these volunteers engaged in health interventions activities at the community level. This study assessed the level of performance and factors that affect the performance of health volunteers’ activities in Northern Ghana. Methods: This was a cross-sectional study using quantitative method of data collection. Two hundred structured interviews were conducted with health volunteers. Data collectors visited health volunteers at home and conducted the interviews after informed consent was obtained. STATA Version 11.2 was used to analyze the data. Descriptive statistics were used to assess the level of performance of the health volunteers. Multiple logistic regression models were then used to assess factors that influence the performance of health volunteers. Results: About 45% of volunteers scored high on performance. In the multivariate analysis, educational status [OR = 4.64 95% CI (1.22–17.45)] and ethnicity [OR = 1.85 95% CI (1.00–3.41)] were the factors that influenced the performance of health volunteers. Other intermediary factors such as incentives and means of transport also affected the performance of health volunteers engaged in health intervention activities at the community level. Conclusion: The results suggest that higher educational status of health volunteers is more likely to increase their performance. In addition, providing non-monetary incentives and logistics such as bicycles, raincoats, torch lights and wellington boots will enhance the performance of health volunteers and also motivate them to continue to provide health services to their own people at the community level. [ABSTRACT FROM AUTHOR]

T1 sagittal angle has been reported to be used as a parameter for assessing sagittal balance and cervical lordosis. However, no study has been performed to explore the relationship between T1 sagittal angle and sagittal balance, and whether T1 sagittal angle could be used for osteotomy guidelines remains unknown. The aim of our study is to explore the relationship between T1 sagittal angle and sagittal balance, determine the predictors for T1 sagittal angle, and determine whether T1 sagittal angle could be used for osteotomy guidelines to restore sagittal balance. Medical records of healthy volunteers in our outpatient clinic from January 2014 to August 2015 were reviewed, and their standing full-spine lateral radiographs were evaluated. Demographic and radiological parameters were collected and analyzed, including age, gender, T1 sagittal angle, maxTK, maxLL, SS, PT, and PI. Correlation coefficients between T1 sagittal angle and other spinopelvic parameters were determined. In addition, multiple regression analysis was performed to establish predictive radiographic parameters for T1 sagittal angle as the primary contributors. A total of 119 healthy volunteers were recruited in our study with a mean age of 34.7 years. It was found that T1 sagittal angle was correlated with maxTK with very good significance (r = 0.697, P<0.001), maxLL with weak significance (r = 0.206, P = 0.024), SS with weak significance (r = 0.237, P = 0.009), PI with very weak significance (r = 0.189, P = 0.039), SVA with moderate significance (r = 0.445, P<0.001), TPA with weak significance (r = 0.207, P = 0.023), and T1SPI with weak significance (r = 0.309, P = 0.001). The result of multiple regression analysis showed that T1 sagittal angle could be predicted by using the following regression equation: T1 sagittal angle = 0.6 * maxTK—0.2 * maxLL + 8. In the healthy population, T1 sagittal angle could be considered as a useful parameter for sagittal balance; however, it could not be thoroughly replaced for SVA. maxTK was the primary contributor to T1 sagittal angle. According to this equation, we could restore sagittal balance by surgically changing thoracic kyphosis and lumbar lordosis, which could serve as a guideline for osteotomy. [ABSTRACT FROM AUTHOR]

In Compressed Sensing (CS) of MRI, optimization of the regularization parameters is not a trivial task. We aimed to establish a method that could determine the optimal weights for regularization parameters in CS of time-of-flight MR angiography (TOF-MRA) by comparing various image metrics with radiologists’ visual evaluation. TOF-MRA of a healthy volunteer was scanned using a 3T-MR system. Images were reconstructed by CS from retrospectively under-sampled data by varying the weights for the L1 norm of wavelet coefficients and that of total variation. The reconstructed images were evaluated both quantitatively by statistical image metrics including structural similarity (SSIM), scale invariant feature transform (SIFT) and contrast-to-noise ratio (CNR), and qualitatively by radiologists’ scoring. The results of quantitative metrics and qualitative scorings were compared. SSIM and SIFT in conjunction with brain masks and CNR of artery-to-parenchyma correlated very well with radiologists’ visual evaluation. By carefully selecting a region to measure, we have shown that statistical image metrics can reflect radiologists’ visual evaluation, thus enabling an appropriate optimization of regularization parameters for CS. [ABSTRACT FROM AUTHOR]

MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease opens up a new field for biomarker study. However, diurnal and day-to-day variation in plasma microRNA levels, and differential regulation between males and females, may affect biomarker stability. A QuantStudio 12K Flex Real-Time PCR System was used to profile plasma microRNA levels using OpenArray in male and female healthy volunteers, in the morning and afternoon, and at four time points over a one month period. Using this system we were able to run four OpenArray plates in a single run, the equivalent of 32 traditional 384-well qPCR plates or 12,000 data points. Up to 754 microRNAs can be identified in a single plasma sample in under two hours. 108 individual microRNAs were identified in at least 80% of all our samples which compares favourably with other reports of microRNA profiles in serum or plasma in healthy adults. Many of these microRNAs, including miR-16-5p, miR-17-5p, miR-19a-3p, miR-24-3p, miR-30c-5p, miR-191-5p, miR-223-3p and miR-451a are highly expressed and consistent with previous studies using other platforms. Overall, microRNA levels were very consistent between individuals, males and females, and time points and we did not detect significant differences in levels of microRNAs. These results suggest the suitability of this platform for microRNA profiling and biomarker discovery and suggest minimal confounding influence of sex or sample timing. However, the platform has not been subjected to rigorous validation which must be demonstrated in future biomarker studies where large differences may exist between disease and control samples. [ABSTRACT FROM AUTHOR]

Introduction: The mechanical properties of hamstring muscles are usually inferred from global passive torque/angle relationships, in combination with adjoining tissues crossing the joint investigated. Shear modulus measurement provides an estimate of changes in muscle-tendon stiffness and passive tension. This study aimed to assess the passive individual behavior of each hamstring muscle in different stretching positions using shear wave elastography. Methods/Results: The muscle shear modulus of each hamstring muscle was measured during a standardized slow passive knee extension (PKE, 80% of maximal range of motion) on eighteen healthy male volunteers. Firstly, we assessed the reliability of the measurements. Results were good for semitendinosus (ST, CV: 8.9%-13.4%), semimembranosus (SM, CV: 10.3%-11.2%) and biceps femoris long-head (BF-lh, CV: 8.6%-13.3%), but not for biceps femoris short-head (BF-sh, CV: 20.3%-44.9%). Secondly, we investigated each reliable muscle in three stretch positions: 70°, 90° and 110° of hip flexion. The results showed different values of shear modulus for the same amount of perceived stretch, with the highest measurements in the high-flexed hip situation. Moreover, individual muscles displayed different values, with values increasing or BF-lh, SM and ST, respectively. The inter-subject variability was 35.3% for ST, 27.4% for SM and 30.2% for BF-lh. Conclusion: This study showed that the hip needs to be high-flexed to efficiently tension the hamstrings, and reports a higher muscle-tendon stress tolerance at 110° of hip angle. In addition muscles have different passive behaviors, and future works will clarify if it can be linked with rate of injury. [ABSTRACT FROM AUTHOR]

Background: Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Methods: Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Results: Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Conclusion: Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen’s κ, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study. [ABSTRACT FROM AUTHOR]

Background: It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels. Methods: Cold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 – 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit. Results: CPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively. Conclusions: The localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 – 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically determined patterns from pain phenotype data. [ABSTRACT FROM AUTHOR]

The interruptive effect of painful experimental stimulation on cognitive processes is a well-known phenomenon. This study investigated the influence of pain duration on the negative effects of pain on cognition. Thirty-four healthy volunteers performed a rapid serial visual presentation task (RSVP) in which subjects had to detect (visual detection task) and count the occurrence of a target letter (working memory task) in two separate sessions while being stimulated on the left volar forearm with either short (2 sec) or long (18 sec) painful heat stimuli of equal subjective intensity. The results show that subjects performed significantly worse in the long pain session as indexed by decreased detection and counting performance. Interestingly, this effect on performance was also observed during control trials of the long pain session in which participants did not receive any painful stimulation. Moreover, subjects expected long painful stimulation to have a greater impact on their performance and individual expectation correlated with working memory performance. These findings suggest that not only the length of painful stimulation but also its expected ability to impair cognitive functioning might influence the interruptive function of pain. The exact relevance of expectation for the detrimental effects of pain on cognitive processes needs to be explored in more detail in future studies. [ABSTRACT FROM AUTHOR]

Background: It is difficult to experimentally infect volunteers with RV strains to which the subject demonstrates serological immunity. However, in RV challenges, viral clearance begins before de novo adaptive immune responses would develop. We speculated that adaptive immunity to RV reflects heterologous immunity by effector memory cells. Methods: DCs were generated from monocytes using GM-CSF and IL-4 and RV39 loading accomplished with a dose of ∼350 TCID50/105 cells. RV-induced maturation was established as modulation of MHC class II, CD80, CD83, and CD86. Circulating RV targeting CD4 and CD8 T cells were investigated as induction of RV-specific proliferation (CFSE-dilution). Results: Maturation of DC by RV was confirmed as upregulation of MHC Class II (83.3±5.0% to 87.8±4.1%), CD80 (39.4±7.2% to 47.6±7.7%) and CD86 (78.4±4.7% to 84.1±3.4%). Both CD4 and CD8 memory T cells were recognized in the circulation of healthy subjects. Conclusions: RV drives DC maturation and results in their ability to present RV antigens to both T helper and cytotoxic lymphocytes. Both CD4 and CD8 cells capable of recognizing RV-associated antigens are present in the circulation of healthy subjects where they are presumably involved in immune surveillance and explain the rapid recruitment of an adaptive immune response during RV infection. [ABSTRACT FROM AUTHOR]

Purpose: To determine using swept-source optical coherence tomography (SS-OCT) whether there are differences in the location of the anterior lamina cribrosa insertion (ALI) in primary open-angle glaucoma (POAG) patients and healthy subjects. Methods: Fifty three eyes from 53 patients with POAG, and 53 eyes from 53 age-matched healthy subjects were included prospectively in Seoul National University Bundang Hospital. Twelve radial line B-scans centered on the optic disc in every half-clock-hour meridian were acquired using SS-OCT. The ALI position was assessed by measuring two parameters: (1) ALI distance (ALID)—the distance from the anterior scleral canal opening (ASCO) to the ALI; and (2) marginal anterior lamina cribrosa surface depth (mALCSD)—the perpendicular distance from the ASCO plane to the anterior lamina cribrosa surface. These parameters were compared between the two groups for each meridian. Results: Both ALID (256±54 vs. 209±37 µm, mean ± SD, p<0.001) and mALCSD (232±63 vs. 187±40 µm, p<0.001) were significantly greater in the POAG group than in the normal group. The largest difference was observed at the 6.5 o′clock and 11.5 o′clock meridians for both ALID and mALCSD. Multiple regression analysis revealed a negative correlation between age and both ALID and mALCSD in the control group, and a negative correlation between mean deviation of the visual field test and both ALID and mALCSD in the POAG group. Conclusions: The ALI was displaced posteriorly in eyes with POAG compared to those of healthy controls. This finding suggests that the posteriorly located lamina cribrosa insertion is an important component of glaucomatous optic nerve excavation. [ABSTRACT FROM AUTHOR]

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions. [ABSTRACT FROM AUTHOR]

We investigated the impact of temporary food restriction on a set shifting task requiring participants to judge clusters of pictures against a frequently changing rule. 60 healthy female participants underwent two testing sessions: once after fasting for 16 hours and once in a satiated state. Participants also completed a battery of questionnaires (Hospital Anxiety and Depression Scale [HADS]; Persistence, Perseveration and Perfectionism Questionnaire [PPPQ-22]; and Eating Disorders Examination Questionnaire [EDE-Q6]). Set shifting costs were significantly increased after fasting; this effect was independent of self-reported mood and perseveration. Furthermore, higher levels of weight concern predicted a general performance decrement under conditions of fasting. We conclude that relatively short periods of fasting can lead to set shifting impairments. This finding may have relevance to studies of development, individual differences, and the interpretation of psychometric tests. It also could have implications for understanding the etiology and maintenance of eating disorders, in which impaired set shifting has been implicated. [ABSTRACT FROM AUTHOR]

Background: Uptake of VMMC among adult men has been lower than desired in Nyanza, Kenya. Previous research has identified several barriers to uptake but qualitative exploration of barriers is limited and evidence-informed interventions have not been fully developed. This study was conducted in 2012 to 1) increase understanding of barriers to VMMC and 2) to inform VMMC rollout through the identification of evidence-informed interventions among adult men at high risk of HIV in Nyanza Province, Kenya. Methods: Focus groups (n = 8) and interviews were conducted with circumcised (n = 8) and uncircumcised men (n = 14) from the two districts in Nyanza, Kenya. Additional interviews were conducted with female partners (n = 20), health providers (n = 12), community leaders (n = 12) and employers (n = 12). Interview and focus group guides included questions about individual, interpersonal and societal barriers to VMMC uptake and ways to overcome them. Inductive thematic coding and analysis were conducted through a standard iterative process. Results: Two primary concerns with VMMC emerged 1) financial issues including missing work, losing income during the procedure and healing and family survival during the recovery period and 2) fear of pain during and after the procedure. Key interventions to address financial concerns included: a food or cash transfer, education on saving and employer-based benefits. Interventions to address concerns about pain included refining the content of demand creation and counseling messages about pain and improving the ways these messages are delivered. Conclusions: Men need accurate and detailed information on what to expect during and after VMMC regarding both pain and time away from work. This information should be incorporated into demand creation activities for men considering circumcision. Media content should frankly and correctly address these concerns. Study findings support scale up and/or further improvement of these ongoing educational programs and specifically targeting the demand creation period. [ABSTRACT FROM AUTHOR]

Chronic periodontitis is one of the most common forms of biofilm-induced diseases. Most of the recent studies were focus on the dental plaque microbial diversity and microbiomes. However, analyzing bacterial diversity at the taxonomic level alone limits deeper comprehension of the ecological relevance of the community. In this study, we compared the metabolic functional diversity of the microbial community in healthy subjects and periodontitis patients in a creative way—to assess the sole carbon source utilization using Biolog assay, which was first applied on oral micro-ecology assessment. Pattern analyses of 95-sole carbon sources catabolism provide a community-level phenotypic profile of the microbial community from different habitats. We found that the microbial community in the periodontitis group had greater metabolic activity compared to the microbial community in the healthy group. Differences in the metabolism of specific carbohydrates (e.g. β-methyl-D-glucoside, stachyose, maltose, D-mannose, β-methyl-D-glucoside and pyruvic acid) were observed between the healthy and periodontitis groups. Subjects from the healthy and periodontitis groups could be well distinguished by cluster and principle component analyses according to the utilization of discriminate carbon sources. Our results indicate significant difference in microbial functional diversity between healthy subjects and periodontitis patients. We also found Biolog technology is effective to further our understanding of community structure as a composite of functional abilities, and it enables the identification of ecologically relevant functional differences among oral microbial communities. [ABSTRACT FROM AUTHOR]

The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria. [ABSTRACT FROM AUTHOR]

Background: Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods: We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results: Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions: BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration: ClinicalTrials.gov NCT01188512 [ABSTRACT FROM AUTHOR]

Background: Patients with a diagnosis of schizophrenia are socially excluded. The aim of this study was to investigate how patients participate in first encounters with unfamiliar healthy participants, who are unaware of their diagnosis. Methods: Patterns of participation were investigated during interactions involving three-people. Three conversation roles were analysed: (i) speaker, (ii) primary recipient- focus of the speaker’s attention and (iii) secondary recipient- unaddressed individual. Twenty patient interactions (1 patient, 2 healthy controls) and 20 control interactions (3 healthy participants) were recorded and motion captured in 3D. The participation of patients and their partners, in each conversation role, was compared with controls at the start, middle and end of the interaction. The relationship between patients’ participation, their symptoms and the rapport others experienced with them was also explored. Results: At the start of the interaction patients spoke less (ß = −.639, p = .02) and spent more time as secondary recipient (ß = .349, p = .02). Patients’ participation at the middle and end of the interaction did not differ from controls. Patients’ partners experienced poorer rapport with patients who spent more time as a primary recipient at the start of the interaction (Rho(11) = −.755, p<.01). Patients’ participation was not associated with symptoms. Conclusion: Despite their increased participation over time, patients’ initial participation appears to be associated with others’ experience of rapport with them. Thus, the opening moments of patients’ first encounters appear to be interpersonally significant. Further investigation of patient and others’ behaviour during these critical moments is warranted in order to understand, and possibly develop interventions to address, the difficulties schizophrenia patients experience here. [ABSTRACT FROM AUTHOR]

Introduction: Measurement of optic nerve sheath diameter (ONSD) by ultrasound is increasingly used as a marker to detect raised intracranial pressure (ICP). ONSD varies with age and there is no clear consensus between studies for an upper limit of normal. Knowledge of normal ONSD in a healthy population is essential to interpret this measurement. Methods: In a prospective observational study, ONSD was measured using a 15 MHz ultrasound probe in healthy volunteers in Chittagong, Bangladesh. The aims were to determine the normal range of ONSD in healthy Bangladeshi adults and children, compare measurements in males and females, horizontal and vertical beam orientations and left and right eyes in the same individual and to determine whether ONSD varies with head circumference independent of age. Results: 136 subjects were enrolled, 12.5% of whom were age 16 or under. Median ONSD was 4.41 mm with 95% of subjects in the range 4.25–4.75 mm. ONSD was bimodally distributed. There was no relationship between ONSD and age (≥4 years), gender, head circumference, and no difference in left vs right eye or horizontal vs vertical beam. Conclusions: Ultrasonographic ONSD in Bangladeshi healthy volunteers has a narrow bimodal distribution independent of age (≥4 years), gender and head circumference. ONSD >4.75 mm in this population should be considered abnormal. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation. Objective: The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects. Methods: Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis. Results: Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R2 = 0.492 for HPT, R2 = 0.538 for PPT, R2 = 0.558 for HPTo and R2 = 0.584 for PPTo). Conclusions: The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. : Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). : IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre. [ABSTRACT FROM AUTHOR]

Background: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. Methods: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). Results and Conclusions: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons. [ABSTRACT FROM AUTHOR]

Background:Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design:Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods:Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results:Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions:Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration:Clinicaltrials.gov number NCT00931346 [ABSTRACT FROM AUTHOR]