Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Encoding of 3D physical dimensions by face-selective cortical neurons.

Neurons throughout the primate inferior temporal (IT) cortex respond selectively to visual images of faces and other complex objects. The response magnitude of neurons to a given image often depends on the size at which the image is presented, usually on a flat display at a fixed distance. While such size sensitivity might simply reflect the angular subtense of retinal image stimulation in degrees, one unexplored possibility is that it tracks the real-world geometry of physical objects, such as their size and distance to the observer in centimeters. This distinction bears fundamentally on the nature of object representation in IT and on the scope of visual operations supported by the ventral visual pathway. To address this question, we assessed the response dependency of neurons in the macaque anterior fundus (AF) face patch to the angular versus physical size of faces. We employed a macaque avatar to stereoscopically render three-dimensional (3D) photorealistic faces at multiple sizes and distances, including a subset of size/distance combinations designed to cast the same size retinal image projection. We found that most AF neurons were modulated principally by the 3D physical size of the face rather than its two-dimensional (2D) angular size on the retina. Further, most neurons responded strongest to extremely large and small faces, rather than to those of normal size. Together, these findings reveal a graded encoding of physical size among face patch neurons, providing evidence that category-selective regions of the primate ventral visual pathway participate in a geometric analysis of real-world objects.

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment.

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain's primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.

The Association Between Peripheral Oxytocin Levels and Depressive Symptoms in People With HIV.

OBJECTIVE: Depression is common in people with HIV (PWH), yet little is known about the mechanisms contributing to depressive symptoms in PWH. Previous research across a range of populations has suggested a relationship between the neuropeptide oxytocin and depressive symptoms, with variable directionality. This article investigated the association between peripheral oxytocin levels and depressive symptoms in PWH. METHODS: Unextracted oxytocin serum concentrations were assayed in 79 PWH (44% female, mean age = 34.35 [8.5], mean body mass index = 25.69 [5.46], mean CD4 = 516.60 [271.15]) who also completed the Center for Epidemiologic Studies Depression Scale (CES-D). CES-D items were evaluated in an exploratory factor analysis (EFA), and the relationships between oxytocin, total CES-D score, and the resulting EFA factors were analyzed with multivariate linear regressions conducted in R. Multiple regression models were used to adjust for age, sex, body mass index, CD4, and education. RESULTS: Contrary to hypothesized, higher peripheral oxytocin levels were associated with higher CES-D total scores with a small-to-moderate effect size ( ß = 0.26, p = .009). Following Bonferroni correction, oxytocin was not significantly associated with any of the five factors identified from the EFA: depressed affect, positive affect, appetite, cognitive symptoms, or perceived failure ( p values > .042). Small effect sizes were found for the depressed affect ( ß = 0.22) and perceived failure ( ß = 0.21) factors ( p values > .042). CONCLUSIONS: In a sample of predominately Black or African American individuals with HIV, higher oxytocin was associated with higher total depressive symptoms. In addition, this relationship was slightly stronger than those of specific depressive symptoms. These findings warrant further study into the role of oxytocin in mood symptoms within PWH.

Fuzzy Pattern Tree Evolution Using Grammatical Evolution.

A novel approach to induce Fuzzy Pattern Trees using Grammatical Evolution is presented in this paper. This new method, called Fuzzy Grammatical Evolution, is applied to a set of benchmark classification problems. Experimental results show that Fuzzy Grammatical Evolution attains similar and oftentimes better results when compared with state-of-the-art Fuzzy Pattern Tree composing methods, namely Fuzzy Pattern Trees evolved using Cartesian Genetic Programming, on a set of benchmark problems. We show that, although Cartesian Genetic Programming produces smaller trees, Fuzzy Grammatical Evolution produces better performing trees. Fuzzy Grammatical Evolution also benefits from a reduction in the number of necessary user-selectable parameters, while Cartesian Genetic Programming requires the selection of three crucial graph parameters before each experiment. To address the issue of bloat, an additional version of Fuzzy Grammatical Evolution using parsimony pressure was tested. The experimental results show that Fuzzy Grammatical Evolution with this extension routinely finds smaller trees than those using Cartesian Genetic Programming without any compromise in performance. To improve the performance of Fuzzy Grammatical Evolution, various ensemble methods were investigated. Boosting was seen to find the best individuals on half the benchmarks investigated.

Novel tip-loaded dissolving and implantable microneedle array patches for sustained release of finasteride.

Finasteride (FND) is a competitive inhibitor of 5α-reductase, an enzyme involved in benign prostatic hyperplasia (BPH) and androgenic alopecia. FND is administered in oral, often lifelong treatments, increasing the pill burden of polymedicated patients. Microneedle array patches (MAPs) are minimally invasive devices that painlessly pierce the outermost layers of the skin, forming slowly-dissolving drug depots in the dermis, which can release drugs over weeks or months, making this platform an attractive, patient-friendly option for long-term treatments. This work describes the development of long-acting dissolving and implantable PLGA MAPs aimed for systemic release of FND for at least two weeks. Mechanically strong tip-loaded MAPs with pyramidal geometry were obtained using micromoulding methodology. In vitro studies revealed that the dissolving and implantable MAPs were able to release the drug for over 7 and 14 days, respectively. Skin deposition experiments in Franz cells demonstrated that after 24 h, dissolving and implantable MAPs were able to deposit 629.00 ± 214.54 µg and 1861.64 ± 383.30 µg of FND in the skin, respectively. On the other hand, transdermal permeation studies showed that both formulations produced a slow release of the drug to the receptor compartment of the Franz cells, with dissolving and implantable MAPs releasing 90.43 ± 6.20 µg and 27.80 ± 3.94 µg of FND after 24 h. The formulations described here could be an alternative to current oral treatments, having the potential to deliver the drug for extended periods, simplifying the treatment of BPH and androgenic alopecia.

Equivalent Impedance Models for Electrochemical Nanosensor-Based Integrated System Design.

Models of electrochemical sensors play a critical role for electronic engineers in designing electrochemical nanosensor-based integrated systems and are also widely used in analyzing chemical reactions to model the current, electrical potential, and impedance occurring at the surface of an electrode. However, the use of jargon and the different perspectives of scientists and electronic engineers often result in different viewpoints on principles of electrochemical models, which can impede the effective development of sensor technology. This paper is aimed to fill the knowledge gap between electronic engineers and scientists by providing a review and an analysis of electrochemical models. First, a brief review of the electrochemical sensor mechanism from a scientist's perspective is presented. Then a general model, which reflects a more realistic situation of nanosensors is proposed from an electronic engineer point of view and a comparison between the Randles Model is given with its application in electrochemical impedance spectroscopy and general sensor design. Finally, with the help of the proposed equivalent model, a cohesive explanation of the scan rate of cyclic voltammetry is discussed. The information of this paper can contribute to enriching the knowledge of electrochemical sensor models for scientists and is also able to guide the electronic engineer on designing next-generation sensor layouts.

Advanced Solid State Nano-Electrochemical Sensors and System for Agri 4.0 Applications.

Global food production needs to increase in order to meet the demands of an ever growing global population. As resources are finite, the most feasible way to meet this demand is to minimize losses and improve efficiency. Regular monitoring of factors like animal health, soil and water quality for example, can ensure that the resources are being used to their maximum efficiency. Existing monitoring techniques however have limitations, such as portability, turnaround time and requirement for additional reagents. In this work, we explore the use of micro- and nano-scale electrode devices, for the development of an electrochemical sensing platform to digitalize a wide range of applications within the agri-food sector. With this platform, we demonstrate the direct electrochemical detection of pesticides, specifically clothianidin and imidacloprid, with detection limits of 0.22 ng/mL and 2.14 ng/mL respectively, and nitrates with a detection limit of 0.2 µM. In addition, interdigitated electrode structures also enable an in-situ pH control technique to mitigate pH as an interference and modify analyte response. This technique is applied to the analysis of monochloramine, a common water disinfectant. Concerning biosensing, the sensors are modified with bio-molecular probes for the detection of both bovine viral diarrhea virus species and antibodies, over a range of 1 ng/mL to 10 µg/mL. Finally, a portable analogue front end electronic reader is developed to allow portable sensing, with control and readout undertaken using a smart phone application. Finally, the sensor chip platform is integrated with these electronics to provide a fully functional end-to-end smart sensor system compatible with emerging Agri-Food digital decision support tools.

Hyperarousal symptoms and decreased right hemispheric frontolimbic white matter integrity predict poorer sleep quality in combat-exposed veterans.

OBJECTIVE: Disrupted sleep is common following combat deployment. Contributors to risk include posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI); however, the mechanisms linking PTSD, mTBI, and sleep are unclear. Both PTSD and mTBI affect frontolimbic white matter tracts, such as the uncinate fasciculus. The current study examined the relationship between PTSD symptom presentation, lateralized uncinate fasciculus integrity, and sleep quality. METHOD: Participants include 42 combat veterans with and without PTSD and mTBI. Freesurfer and Tracula were used to establish specific white matter ROI integrity via 3-T MRI. The Pittsburgh Sleep Quality Index and PTSD Checklist were used to assess sleep quality and PTSD symptoms. RESULTS: Decreased fractional anisotropy in the right uncinate fasciculus (ß = -1.11, SE = 0.47, p < .05) and increased hyperarousal symptom severity (ß = 3.50, SE = 0.86, p < .001) were associated with poorer sleep quality. CONCLUSION: Both right uncinate integrity and hyperarousal symptom severity are associated withsleep quality in combat veterans. The right uncinate is a key regulator of limbic behavior and sympathetic nervous system reactivity, a core component of hyperarousal. Damage to this pathway may be one mechanism by which mTBI and/or PTSD could create vulnerability for sleep problems following combat deployment.

Posttraumatic Stress Disorder Subsequent to Apparent Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds. Years later, he developed severe PTSD after combat exposure. He was not receiving clinical services for these issues but was encountered in the context of a research study. We conducted cognitive, autonomic, and MRI assessments to assess brain function, structure, and neurophysiology. Next, we compared amygdala volume, uncinate fasciculus diffusion, functional connectivity, facial affect recognition, and baroreceptor coherence with those of a control group of combat veterans (n = 23). Our veteran's MRI revealed a large right medial-orbital prefrontal lesion with surrounding atrophy, which the study neuroradiologist interpreted as likely caused by traumatic injury. Comparison with controls indicated disrupted structural and functional connectivity of prefrontal-limbic structures and impaired emotional, cognitive, and autonomic responses. Detection of this injury before combat would have been unlikely in a clinical context because our veteran had reported a phenomenologically mild injury, and PTSD is a simple explanation for substance abuse, sleep impairment, and psychosocial distress. However, it may be that right prefrontal-limbic disruption imparted vulnerability for the development of PTSD and exacerbated our veteran's emotional response to, and recovery from, PTSD.

Audiovisual integration in macaque face patch neurons.

Primate social communication depends on the perceptual integration of visual and auditory cues, reflected in the multimodal mixing of sensory signals in certain cortical areas. The macaque cortical face patch network, identified through visual, face-selective responses measured with fMRI, is assumed to contribute to visual social interactions. However, whether face patch neurons are also influenced by acoustic information, such as the auditory component of a natural vocalization, remains unknown. Here, we recorded single-unit activity in the anterior fundus (AF) face patch, in the superior temporal sulcus, and anterior medial (AM) face patch, on the undersurface of the temporal lobe, in macaques presented with audiovisual, visual-only, and auditory-only renditions of natural movies of macaques vocalizing. The results revealed that 76% of neurons in face patch AF were significantly influenced by the auditory component of the movie, most often through enhancement of visual responses but sometimes in response to the auditory stimulus alone. By contrast, few neurons in face patch AM exhibited significant auditory responses or modulation. Control experiments in AF used an animated macaque avatar to demonstrate, first, that the structural elements of the face were often essential for audiovisual modulation and, second, that the temporal modulation of the acoustic stimulus was more important than its frequency spectrum. Together, these results identify a striking contrast between two face patches and specifically identify AF as playing a potential role in the integration of audiovisual cues during natural modes of social communication.

Parallel Processing of Facial Expression and Head Orientation in the Macaque Brain.

When we move the features of our face, or turn our head, we communicate changes in our internal state to the people around us. How this information is encoded and used by an observer's brain is poorly understood. We investigated this issue using a functional MRI adaptation paradigm in awake male macaques. Among face-selective patches of the superior temporal sulcus (STS), we found a double dissociation of areas processing facial expression and those processing head orientation. The face-selective patches in the STS fundus were most sensitive to facial expression, as was the amygdala, whereas those on the lower, lateral edge of the sulcus were most sensitive to head orientation. The results of this study reveal a new dimension of functional organization, with face-selective patches segregating within the STS. The findings thus force a rethinking of the role of the face-processing system in representing subject-directed actions and supporting social cognition.SIGNIFICANCE STATEMENT When we are interacting with another person, we make inferences about their emotional state based on visual signals. For example, when a person's facial expression changes, we are given information about their feelings. While primates are thought to have specialized cortical mechanisms for analyzing the identity of faces, less is known about how these mechanisms unpack transient signals, like expression, that can change from one moment to the next. Here, using an fMRI adaptation paradigm, we demonstrate that while the identity of a face is held constant, there are separate mechanisms in the macaque brain for processing transient changes in the face's expression and orientation. These findings shed new light on the function of the face-processing system during social exchanges.

Mapping Reaction-Diffusion Networks at the Plant Wound Site With Pathogens.

The rich collection of microbes colonizing the plant root making up the rhizosphere function as a multigenomic organ for nutrient distribution. The extent to which its dynamic mutualistic cellular order depends on morphogenic signaling, while likely, remains unknown. We have shown that reaction-diffusion chemical networks constructed with model plant and bacterial metabolites can mimic processes ranging from oxidative burst kinetics to traveling waves and extracellular stationary state reaction-diffusion networks for spatiotemporal ordering of the rhizosphere. Plant parasites and pathogens can be limited by host attachment require dynamic informational networks and continue to provide insight into what controls the rhizosphere. Here we take advantage of Agrobacterium tumefaciens, a plant pathogen with a gated receptor that requires simultaneous perception of two plant metabolites. Genetic manipulations have created receptors allowing each metabolite concentration to be correlated with pathogen behavior. The development of the florescent strains used here provide initial maps of the reaction-diffusion dynamics existing in the rhizosphere, revealing significant differences in the signaling landscape of host and non-host plants before and after wounding, specifically highlighting networks that may inform rhizosphere organization.

The Fabrication and in vitro Evaluation of Retinoic Acid-Loaded Electrospun Composite Biomaterials for Tracheal Tissue Regeneration.

Although relatively rare, major trauma to the tracheal region of the airways poses a significant clinical challenge with few effective treatments. Bioengineering and regenerative medicine strategies have the potential to create biocompatible, implantable biomaterial scaffolds, with the capacity to restore lost tissue with functional neo-trachea. The main goal of this study was to develop a nanofibrous polycaprolactone-chitosan (PCL-Chitosan) scaffold loaded with a signaling molecule, all-trans retinoic acid (atRA), as a novel biomaterial approach for tracheal tissue engineering. Using the Spraybase® electrospinning platform, polymer concentration, solvent selection, and instrument parameters were optimized to yield a co-polymer with nanofibers of 181-197 nm in diameter that mimicked tracheobronchial tissue architecture. Thereafter, scaffolds were assessed for their biocompatibility and capacity to induce mucociliary functionalization using the Calu-3 cell line. PCL-Chitosan scaffolds were found to be biocompatible in nature and support Calu-3 cell viability over a 14 day time period. Additionally, the inclusion of atRA did not compromise Calu-3 cell viability, while still achieving an efficient encapsulation of the signaling molecule over a range of atRA concentrations. atRA release from scaffolds led to an increase in mucociliary gene expression at high scaffold loading doses, with augmented MUC5AC and FOXJ1 detected by RT-PCR. Overall, this scaffold integrates a synthetic polymer that has been used in human tracheal stents, a natural polymer generally regarded as safe (GRAS), and a drug with decades of use in patients. Coupled with the scalable nature of electrospinning as a fabrication method, all of these characteristics make the biomaterial outlined in this study amenable as an implantable device for an unmet clinical need in tracheal replacement.

Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.

Actinin-1 mutations cause dominantly inherited congenital macrothrombocytopenia (CMTP), with mutations in the actin-binding domain increasing actinin's affinity for F-actin. In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro. Mutations within the calmodulin-like domain decrease its thermal stability slightly but do not dramatically affect calcium binding, with mutant proteins retaining calcium-dependent regulation of filament bundling in vitro. The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells. Thus, CMTP-causing actinin-1 mutations outside the actin-binding domain also increase actin association, suggesting a common molecular mechanism underlying actinin-1 related CMTP.

Improved Accuracy on Lateralized Spatial Judgments in Healthy Aging.

OBJECTIVES: Healthy young adults often demonstrate a leftward spatial bias called "pseudoneglect" which often diminishes with aging. One hypothesis for this phenomenon is an age-related deterioration in right hemisphere functions (right hemi-aging). If true, then a greater rightward bias should be evident on all spatial attention tasks regardless of content. Another hypothesis is a decrease in asymmetrical hemispheric activation with age (HAROLD). If true, older participants may show reduced bias in all spatial tasks, regardless of leftward or rightward biasing of specific spatial content. METHODS: Seventy right-handed healthy participants, 33 younger (21-40) and 37 older (60-78), were asked to bisect solid and character-letter lines as well as to perform left and right trisections of solid lines. RESULTS: Both groups deviated toward the left on solid line bisections and left trisections. Both groups deviated toward the right on right trisections and character line bisections. In all tasks, the older participants were more accurate than the younger participants. CONCLUSIONS: The finding that older participants were more accurate than younger participants across all bisection and trisection conditions suggests a decrease in the asymmetrical hemispheric activation of these specialized networks important in the allocation of contralateral spatial attention or spatial action intention.

A parameterized digital 3D model of the Rhesus macaque face for investigating the visual processing of social cues.

BACKGROUND: Rhesus macaques are the most popular model species for studying the neural basis of visual face processing and social interaction using intracranial methods. However, the challenge of creating realistic, dynamic, and parametric macaque face stimuli has limited the experimental control and ethological validity of existing approaches. NEW METHOD: We performed statistical analyses of in vivo computed tomography data to generate an anatomically accurate, three-dimensional representation of Rhesus macaque cranio-facial morphology. The surface structures were further edited, rigged and textured by a professional digital artist with careful reference to photographs of macaque facial expression, colouration and pelage. RESULTS: The model offers precise, continuous, parametric control of craniofacial shape, emotional expression, head orientation, eye gaze direction, and many other parameters that can be adjusted to render either static or dynamic high-resolution faces. Example single-unit responses to such stimuli in macaque inferotemporal cortex demonstrate the value of parametric control over facial appearance and behaviours. COMPARISON WITH EXISTING METHOD(S): The generation of such a high-dimensionality and systematically controlled stimulus set of conspecific faces, with accurate craniofacial modelling and professional finalization of facial details, is currently not achievable using existing methods. CONCLUSIONS: The results herald a new set of possibilities in adaptive sampling of a high-dimensional and socially meaningful feature space, thus opening the door to systematic testing of hypotheses about the abundant neural specialization for faces found in the primate.

Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-Retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection.

Ending the tuberculosis (TB) epidemic by 2030 was recently listed in the United Nations (UN) Sustainable Development Goals alongside HIV/AIDS and malaria as it continues to be a major cause of death worldwide. With a significant proportion of TB cases caused by resistant strains of Mycobacterium tuberculosis (Mtb), there is an urgent need to develop new and innovative approaches to treatment. Since 1989, researchers have been assessing the anti-bacterial effects of the active metabolite of vitamin A, all trans-Retinoic acid (ATRA) solution, in Mtb models. More recently the antibacterial effect of ATRA has been shown to regulate the immune response to infection via critical gene expression, monocyte activation and the induction of autophagy leading to its application as a host-directed therapy (HDT). Inhalation is an attractive route for targeted treatment of TB, and therefore we have developed ATRA-loaded microparticles (ATRA-MP) within the inhalable size range (2.07 ±â€¯0.5 µm) offering targeted delivery of the encapsulated cargo (70.5 ±â€¯2.3%) to the site of action within the alveolar macrophage, which was confirmed by confocal microscopy. Efficient cellular delivery of ATRA was followed by a reduction in Mtb growth (H37Ra) in THP-1 derived macrophages evaluated by both the BACT/ALERT® system and enumeration of colony forming units (CFU). The antibacterial effect of ATRA-MP treatment was further assessed in BALB/c mice infected with the virulent strain of Mtb (H37Rv). ATRA-MP treatments significantly decreased the bacterial burden in the lungs alongside a reduction in pulmonary pathology following just three doses administered intratracheally. The immunomodulatory effects of targeted ATRA treatment in the lungs indicate a distinct yet effective mechanism of action amongst the formulations. This is the first study to-date of a controlled release ATRA treatment for TB suitable for inhalation that offers improved targeting of a HDT, retains antibacterial efficacy and improves pulmonary pathology compared to ATRA solution.

Amygdala lesions eliminate viewing preferences for faces in rhesus monkeys.

In free-viewing experiments, primates orient preferentially toward faces and face-like stimuli. To investigate the neural basis of this behavior, we measured the spontaneous viewing preferences of monkeys with selective bilateral amygdala lesions. The results revealed that when faces and nonface objects were presented simultaneously, monkeys with amygdala lesions had no viewing preference for either conspecific faces or illusory facial features in everyday objects. Instead of directing eye movements toward socially relevant features in natural images, we found that, after amygdala loss, monkeys are biased toward features with increased low-level salience. We conclude that the amygdala has a role in our earliest specialized response to faces, a behavior thought to be a precursor for efficient social communication and essential for the development of face-selective cortex.