Lanka Mahila Samiti, Mary Rutnam and girl's education.

This article engages with the maternal education politics in late colonial Sri Lanka by looking at the implementation of maternal health in the gendered syllabus of middle-class girls' schools. After decades of gender-specific education, the 1930s saw a homogenisation of teachings in these schools through the impact of Mary Rutnam's health manuals. Rutnam was a Canadian doctor who had been living in Sri Lanka for most of her adult life and was seen as a local. She was also active in establishing women's and girls' organisations and political groups. Especially the Lanka Mahila Samiti (LMS) was greatly influential and still is today. The LMS specifically aims at educating the rural women in maternal health and other forms of hygiene with the goal to increase their political and cultural agency. This article examines the relationship between Rutnam's handbooks for girls' schools and the globality of the discourse of motherhood, on the one hand, and the hierarchical divide between the urban middle-class woman and the rural woman, on the other hand. I will argue that by applying the classist discourse of eugenics and hygiene, the teaching of maternal health was transformed in Sri Lanka to create a notion of motherhood that was detached from religion, as it previously was so often framed by it but was highly racialised and classist. This notion of motherhood continues to exist and informs the teaching of sexuality in contemporary Sri Lankan middle-class girls' schools.

AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1.0 × 1013 or 2.5 × 1013 genome copies/kg of an AAV serotype 8 vector expressing a codon-optimized version of human uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) from a liver-specific promoter. We extensively studied vector biodistribution, transgene expression, and immune responses following vector administration. All rhesus macaques survived until their scheduled necropsy at day 56 and showed no clinical abnormalities during the course of the study. Macaques administered with either vector dose developed a T cell response to the AAV capsid and/or transgene. We mapped the immunodominant epitope in the human UGT1A1 sequence, and we found no correlation between peripheral and tissue-resident lymphocyte responses. Upon further investigation, we characterized CD107a+, granzyme B+, CD4+, and CD8+ transgene-specific cellular responses that were restricted to tissue-resident T cells. This study highlights the importance of studying immune responses at the vector transduction site and the limited usefulness of blood as a surrogate to evaluate tissue-restricted T cell responses.

Central Processing of the Chemical Senses: an Overview.

Our knowledge regarding the neural processing of the three chemical senses has been lagging behind that of our other senses considerably. It is only during the last 25 years that significant advances have been made in our understanding of where in the human brain odors, tastants, and trigeminal stimuli are processed. Here we provide an overview of the current knowledge of how the human brain processes chemical stimuli based on findings in neuroimaging studies using positron emission tomography and functional magnetic resonance imaging. Additionally, we provide new insights from recent meta-analyses, based on all published neuroimaging studies of the chemical senses, of where the chemical senses converge in the brain.

Identification of human gustatory cortex by activation likelihood estimation.

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.

Smelling chemosensory signals of males in anxious versus nonanxious condition increases state anxiety of female subjects.

The hypothesis of this experiment was that humans in an anxious state compared with a nonanxious state are able to increase anxiety levels in other humans via their body odors. Specifically, we hypothesized that male chemosensory anxiety signals compared with neutral chemosignals increase state anxiety of female subjects. Thirteen male subjects participated in 2 different sweat donation sessions: chemosignals were collected during participation in a high rope course (anxiety condition) and in an ergometer workout (neutral condition). State and trait anxiety were evaluated in 20 female odor recipients using Spielberger's state-trait anxiety inventory in a double-blind design. Comparison of state anxiety of odor donors between control and anxiety condition differed significantly indicating that our model of anxiety induction successfully led to the expected change in emotion. Comparison of state anxiety of odor recipients showed a trend toward higher state anxiety in the anxiety condition compared with the neutral condition after 5 min of odor exposure. After 20 min of odor exposure, state anxiety of female subjects was significantly higher during the perception of sweat collected during the anxiety condition in comparison with the perception of sweat collected during the neutral condition. This experiment gives evidence that male anxiety chemosignals compared with neutral chemosignals are capable of inducing an increased state anxiety in female subjects.

No fear no risk! Human risk behavior is affected by chemosensory anxiety signals.

An important aspect of cognitive functioning is decision-making, which depends on the correct interpretation of emotional processes. High trait anxiety has been associated with increased risk taking behavior in decision-making tasks. An interesting fact is that anxiety and anxiety-related chemosignals as well as decision-making share similar regions of neuronal activation. In order to ascertain if chemosensory anxiety signals have similar effects on risk taking behavior of healthy participants as high trait anxiety we used a novel computerized decision-making task, called Haegler's Risk Game (HRG). This task measures risk taking behavior based on contingencies and can be played repeatedly without a learning effect. To obtain chemosensory signals the sweat of 21 male donors was collected in a high rope course (anxiety condition). For the chemosensory control condition sweat was collected during an ergometer workout (exercise condition). In a double-blind study, 30 healthy recipients (16 females) had to play HRG while being exposed to sweat samples or empty control samples (control condition) in three sessions of randomized order. Comparison of the risk taking behavior of the three conditions showed significantly higher risk taking behavior in participants for the most risky choices during the anxiety condition compared to the control conditions. Additionally, recipients showed significantly higher latency before making their decision in the most risky choices during the anxiety condition. This experiment gives evidence that chemosensory anxiety signals are communicated between humans thereby increasing participants' risk taking behavior.

Methods for building an inexpensive computer-controlled olfactometer for temporally-precise experiments.

Many human olfactory experiments call for fast and stable stimulus-rise times as well as exact and stable stimulus-onset times. Due to these temporal demands, an olfactometer is often needed. However, an olfactometer is a piece of equipment that either comes with a high price tag or requires a high degree of technical expertise to build and/or to run. Here, we detail the construction of an olfactometer that is constructed almost exclusively with "off-the-shelf" parts, requires little technical knowledge to build, has relatively low price tags, and is controlled by E-Prime, a turnkey-ready and easily-programmable software commonly used in psychological experiments. The olfactometer can present either solid or liquid odor sources, and it exhibits a fast stimulus-rise time and a fast and stable stimulus-onset time. We provide a detailed description of the olfactometer construction, a list of its individual parts and prices, as well as potential modifications to the design. In addition, we present odor onset and concentration curves as measured with a photo-ionization detector, together with corresponding GC/MS analyses of signal-intensity drop (5.9%) over a longer period of use. Finally, we present data from behavioral and psychophysiological recordings demonstrating that the olfactometer is suitable for use during event-related EEG experiments.

The neuronal correlates of intranasal trigeminal function-an ALE meta-analysis of human functional brain imaging data.

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO(2)), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices-a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO(2) stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing.

Echo time dependence of BOLD fMRI studies of the piriform cortex.

BACKGROUND AND PURPOSE: In functional magnetic resonance imaging (fMRI) studies, brain areas that are commonly associated with the processing of olfactory stimuli, i.e., piriform cortex and orbitofrontal cortex, are often obscured by susceptibility-induced signal loss. The authors hypothesized that using a short echo time (TE) should not only reduce susceptibility artifacts but also increase the overall signal-to-noise ratio and allow to retrieve a blood oxygenation level-dependent (BOLD) signal in regions normally affected by these artifacts. MATERIAL AND METHODS: Two sequences with TEs of 60 and 32 ms were compared using a 1.5-T MRI scanner: in a standard motor paradigm, activations of the contralateral motor cortex were measured. In an olfactory stimulation paradigm, activations in piriform cortex were compared. RESULTS: Reducing TE from 60 to 32 ms reduced the observed signal intensity changes in the motor paradigm by 51%. Concomitant to this, geometric distortions and signal dropout artifacts were decreased at orbitofrontal and temporomesial brain areas in both paradigms. Contrary to the authors' expectations, the signal intensity changes in the piriform cortex were also reduced by 48% in the olfactory paradigm. Moreover, piriform cortex activation was detected in less subjects at TE = 32 ms than at TE = 60 ms. Changes in cortical activation were significant in the right, but not in the left piriform cortex. CONCLUSION: Although a shorter TE reduces signal dropouts due to susceptibility artifacts, this shorter TE is not sufficient to recover the BOLD signal from regions affected by susceptibility artifacts such as the piriform cortex. Thus, reducing the TE to the T2* of the investigated region is not an effective approach to improve the results of olfactory fMRI studies.

Activation of primary and secondary somatosensory regions following tactile stimulation of the face.

BACKGROUND: Since the work of Penfield & Rasmussen it is well established that the human primary somatosensory cortex is organized somatotopically. However, the order of the representation of the face is still a matter of discussion, i.e., it is yet unclear whether the face is represented upside-down or vice versa in the somatosensory cortex. MATERIAL AND METHODS: In a functional magnetic resonance imaging study (n = 30), tactile stimuli to three different locations on each side of the face were applied using a pneumatic device. Locations of stimulation corresponded to the three branches of the trigeminal nerve (forehead, cheek, chin). To determine the representation of the face on primary and secondary somatosensory cortices, peak coordinates within these regions were analyzed subjectwise. RESULTS: Contralateral activation of the primary somatosensory cortex following tactile stimulation of the face was found, whereas the secondary somatosensory cortices were activated bilaterally. However, differences between activation coordinates of different tactile stimuli applied to one side of the face were not statistically significant. CONCLUSION: Tactile stimulation of the face leads to contralateral activation of primary and bilateral activation of secondary somatosensory cortices. Using the authors' methodological approach it was not possible to detect a somatotopic organization related to different facial areas.

Neuronal correlates of emotional processing in patients with major depression.

Affective facial processing is an important component of interpersonal relationships, which is altered in patients with major depression. The study was designed to examine differences in functional brain activity between patients with major depression and healthy controls using functional magnetic resonance imaging (fMRI). Twelve patients with major depression and 12 age-, gender- and handedness-matched healthy controls were studied using fMRI. Subjects had to match facial emotional expressions in explicit trials, and gender of the presented faces in implicit trials. Patients showed higher blood oxygen level-dependent (BOLD) responses to implicit emotional stimuli than healthy controls in the left dorsolateral prefrontal cortex and the left precentral gyrus. Patients show a failure of deactivation in ACC, right dorsolateral prefrontal cortex (DLPFC) and right superior frontal cortex. Moreover, they exhibited smaller differences in BOLD responses in the left superior temporal lobe for the implicit contrasted to the explicit task, and in the cerebellum for the explicit contrasted to the implicit task compared to those of controls. Altered activation of the prefrontal cortex and anterior cingulum during emotion processing is a key feature of major depression.

Activation of olfactory and trigeminal cortical areas following stimulation of the nasal mucosa with low concentrations of S(-)-nicotine vapor--an fMRI study on chemosensory perception.

Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system) whereas at higher concentrations nicotine vapor additionally produces burning and stinging sensations in the nose (mediated by the trigeminal system). The objective of this study was to determine whether intranasal stimulation with suprathreshold concentrations of S(-)-nicotine vapor causes brain activation in olfactory cortical areas or if trigeminal cortical areas are also activated. Individual olfactory detection thresholds for S(-)-nicotine were determined in 19 healthy occasional smokers using a computer-controlled air-dilution olfactometer. Functional magnetic resonance images were acquired using a 1.5T MR scanner with applications of nicotine in concentrations at or just above the individual's olfactory detection threshold. Subjects reliably perceived the stimuli as being odorous. Accordingly, activation of brain areas known to be involved in processing of olfactory stimuli was identified. Although most of the subjects never or only rarely observed a burning or painful sensation in the nose, brain areas associated with the processing of painful stimuli were activated in all subjects. This indicates that the olfactory and trigeminal systems are activated during perception of nicotine and it is not possible to completely separate olfactory from trigeminal effects by lowering the concentration of the applied nicotine. In conclusion, even at low concentrations that do not consistently lead to painful sensations, intranasally applied nicotine activates both the olfactory and the trigeminal system.

Reduced perception of bodily signals in anorexia nervosa.

OBJECTIVE: Interoceptive awareness is known to be impaired in eating disorders. To date, it has remained unclear whether this variable is related to the construct of interoceptive sensitivity. Interoceptive sensitivity is considered to be an essential variable in emotional processes. The objective of the study was to elucidate this potential relationship and to clarify whether general interoceptive sensitivity is reduced in anorexia nervosa. METHODS: Using a heartbeat perception task, interoceptive sensitivity was assessed in 28 female patients with anorexia nervosa and 28 matched healthy controls. Questionnaires assessing interoceptive awareness (EDI) and several other variables were also administered. RESULTS: Patients with anorexia nervosa displayed significantly decreased interoceptive sensitivity. They also had more difficulties in interoceptive awareness. CONCLUSIONS: In addition to a decreased ability to recognize certain visceral sensations related to hunger, there is a generally reduced capacity to accurately perceive bodily signals in anorexia nervosa. This highlights the potential importance of interoceptive sensitivity in the pathogenesis of eating disorders.

Olfactory performance of patients with anorexia nervosa and healthy subjects in hunger and satiety.

The aim of this study was to compare the olfactory performance of anorectic patients and healthy controls with regard to the state of satiety. Using the Sniffin' Sticks, sensitivity to a nonfood odor (n-butanol) and to a food-related odor (isoamyl acetate) was assessed in 12 anorectic females and compared with 24 healthy controls. Threshold tests were performed in a hungry as well as in a satiated state, odor discrimination and odor identification only when satiated. Pleasantness of the odors was recorded. In terms of the non-food odor n-butanol, the olfactory sensitivity of anorectic patients and controls did not differ. Patients with anorexia nervosa had a significantly lower detection threshold for the food-related odor, but only in the hungry condition. Anorectic patients showed significant deficits in odor discrimination and identification, and under-evaluated the pleasantness of isoamyl acetate. Our results suggest an impaired projection from secondary to tertiary olfactory structures in anorexia nervosa, based upon the dichotomy of performance between detection threshold and odor discrimination/dentification. The reduced pleasantness of isoamyl acetate indicates a decreased olfactory responsiveness to food stimuli in anorexia nervosa.

Test-retest reliability of the olfactory detection threshold test of the Sniffin' sticks.

The aim of the present study was to investigate the test-retest reliability of the olfactory detection threshold subtest of the Sniffin' Sticks test battery, if administered repeatedly on 4 time points. The detection threshold test was repeatedly conducted in 64 healthy subjects. On the first testing session, the threshold test was accomplished 3 times (T(1) = 0 min, T(2) = 35 min, and T(3) = 105 min), representing a short-term testing. A fourth threshold test was conducted on a second testing session (T(4) = 35.1 days after the first testing session), representing a long-term testing. The average scores for olfactory detection threshold for n-butanol did not differ significantly across the 4 points of time. The test-retest reliability (Pearson's r) between the 4 time points of threshold testing were in a range of 0.43-0.85 (P < 0.01). These results support the notion that the olfactory detection threshold test is a highly reliable method for repeated olfactory testing, even if the test is repeated more than once per day and over a long-term period. It is concluded that the olfactory detection threshold test of the Sniffin' Sticks is suitable for repeated testing during experimental or clinical studies.

Emotional stimulation alters olfactory sensitivity and odor judgment.

Emotions have a strong influence on the perception of visual and auditory stimuli. Only little is known about the relation between emotional stimulation and olfactory functions. The present study investigated the relationship between the presentation of affective pictures, olfactory functions, and sex. Olfactory performance was assessed in 32 subjects (16 male). Olfactory sensitivity was significantly reduced following unpleasant picture presentation for all subjects and following pleasant picture presentation for male subjects only. Pleasantness and intensity ratings of a neutral suprathreshold odor were related to the valence of the pictures: After unpleasant picture presentation, the odor was rated as less pleasant and more intense, whereas viewing positive pictures induced a significant increase in reported odor pleasantness. We conclude that inducing a negative emotional state reduces olfactory sensitivity. A relation to functional deviations within the primary olfactory cortices is discussed.

Reduced olfactory sensitivity in subjects with depressive symptoms.

BACKGROUND: Clinical studies suggest that olfactory sensitivity is reduced in major depression. Nevertheless, only little is known about the relationship between depressive symptoms and olfactory functions in healthy subjects. METHODS: The present study investigated the association between depressive symptoms and olfactory performance in 48 healthy subjects (14 male). First depressive symptoms were assessed using the Beck Depression Inventory, following by olfactory testing. Olfactory threshold and discrimination performance was assessed as well as emotional arousal and pleasantness during the testing procedure. RESULTS: We observed a significant negative correlation between olfactory sensitivity and depressive symptoms while olfactory discrimination was not related to depressive symptoms. LIMITATIONS: The degree of depressive symptoms was assessed by questionnaire. A clinical interview might assess depressive symptoms more accurate. CONCLUSION: We conclude that depressive symptoms are related to a reduced olfactory sensitivity. The observed relation between reduced olfactory sensitivity and depressive symptoms could be mediated by functional deviations within brain structures subserving primary olfactory processing such as amygdala and piriform cortex which is in line with results showing abnormal activity pattern in the amygdala and other brain regions in depression.