T-lymphocyte Tyrosine Hydroxylase Regulates T H 17 T-lymphocytes During Repeated Social Defeat Stress

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (TH17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong associations exist between tyrosine hydroxylase (TH; the rate-limiting enzyme in the synthesis of catecholamines) and pro-inflammatory interleukin 17A (IL-17A) expression within purified T-lymphocytes in a rodent model of psychological trauma. Therefore, we hypothesized that T-lymphocyte-generated catecholamines drive TH17 T-lymphocyte polarization through a mitochondrial superoxide-dependent mechanism during psychological trauma. To test this, T-lymphocyte-specific TH knockout mice (THT-KO) were subjected to psychological trauma utilizing repeated social defeat stress (RSDS). RSDS characteristically increased tumor necrosis factor-α (TNFα), IL-6, IL-17A, and IL-22, however, IL-17A and IL-22 (TH17 produced cytokines) were selectively attenuated in circulation and in T-lymphocytes of THT-KO animals. When activated ex vivo, secretion of IL-17A and IL-22 by THT-KO T-lymphocytes was also found to be reduced, but could be partially rescued with supplementation of norepinephrine specifically. Interestingly, THT-KO T-lymphocytes were still able to polarize to TH17 under exogenous polarizing conditions. Last, contrary to our hypothesis, we found RSDS-exposed THT-KO T-lymphocytes still displayed elevated mitochondrial superoxide, suggesting increased mitochondrial superoxide is upstream of T-lymphocyte TH induction, activity, and TH17 regulation. Overall, these data demonstrate TH in T-lymphocytes plays a critical role in RSDS-induced TH17 T-lymphocytes and offer a previously undescribed regulator of inflammation in RSDS

Autonomic and Redox Imbalance Correlates With T-Lymphocyte Inflammation in a Model of Chronic Social Defeat Stress

Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like and depression-like behavior as has been previously described. The spleens of socially-defeated mice showed significant elevations of NE, tyrosine hydroxylase (TH), and acetylcholinesterase (ACHE) levels, which appeared to be due in part to increased expression within T-lymphocytes. Additionally, T-lymphocytes from stressed animals showed higher levels of pro-inflammatory cytokines and mitochondrial superoxide. Interestingly, in this model system, close associations exist within splenic T-lymphocytes amid the autonomic, inflammatory, and redox environments, but these only weakly correlate with individual behavioral differences among animals suggesting the psychological and physiological manifestations of trauma may not be tightly coupled. Last, we describe, for the first time, elevations in calprotectin levels within T-lymphocytes and in circulation of psychologically stressed animals. Calprotectin correlated with both behavioral and physiological changes after social defeat, suggesting the potential for a new biological marker and/or therapeutic target for psychological trauma and its inflammatory comorbidities

A Vision and Framework for the High Altitude Platform Station (HAPS) Networks of the Future

A High Altitude Platform Station (HAPS) is a network node that operates in the stratosphere at an of altitude around 20 km and is instrumental for providing communication services. Precipitated by technological innovations in the areas of autonomous avionics, array antennas, solar panel efficiency levels, and battery energy densities, and fueled by flourishing industry ecosystems, the HAPS has emerged as an indispensable component of next-generations of wireless networks. In this article, we provide a vision and framework for the HAPS networks of the future supported by a comprehensive and state-of-the-art literature review. We highlight the unrealized potential of HAPS systems and elaborate on their unique ability to serve metropolitan areas. The latest advancements and promising technologies in the HAPS energy and payload systems are discussed. The integration of the emerging Reconfigurable Smart Surface (RSS) technology in the communications payload of HAPS systems for providing a cost-effective deployment is proposed. A detailed overview of the radio resource management in HAPS systems is presented along with synergistic physical layer techniques, including Faster-Than-Nyquist (FTN) signaling. Numerous aspects of handoff management in HAPS systems are described. The notable contributions of Artificial Intelligence (AI) in HAPS, including machine learning in the design, topology management, handoff, and resource allocation aspects are emphasized. The extensive overview of the literature we provide is crucial for substantiating our vision that depicts the expected deployment opportunities and challenges in the next 10 years (next-generation networks), as well as in the subsequent 10 years (next-next-generation networks).Comment: To appear in IEEE Communications Surveys & Tutorial

Technical Challenges in the Clinical Application of Radiomics.

Radiomics is a quantitative approach to medical image analysis targeted at deciphering the morphologic and functional features of a lesion. Radiomic methods can be applied across various malignant conditions to identify tumor phenotype characteristics in the images that correlate with their likelihood of survival, as well as their association with the underlying biology. Identifying this set of characteristic features, called tumor signature, holds tremendous value in predicting the behavior and progression of cancer, which in turn has the potential to predict its response to various therapeutic options. We discuss the technical challenges encountered in the application of radiomics, in terms of methodology, workflow integration, and user experience, that need to be addressed to harness its true potential

Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions

Cyclic vomiting syndrome (CVS) is characterized by severe episodic emesis in adults and children. Cannabinoid hyperemesis syndrome is an increasingly recognized CVS‐like illness that has been associated with chronic cannabis use. There are significant gaps in our understanding of the pathophysiology, clinical features, comorbidities, and effective management options of CVS. Recommendations for treating CVS are based on limited clinical data, as no placebo‐controlled, randomized trials have yet been conducted. Diseases associated with CVS, including migraine, mitochondrial disorders, autonomic dysfunction, and psychiatric comorbidities, provide clues about pathophysiologic mechanisms and suggest potential therapies. We review our current understanding of CVS and propose future research directions with the aim of developing effective therapy. Establishing a multicenter, standardized registry of CVS patients could drive research on multiple fronts including developing CVS‐specific outcome measures to broaden our understanding of clinical profiles, to serve as treatment end points in clinical trials, and to provide a platform for patient recruitment for randomized clinical trials. Such a robust database would also facilitate conduct of research that aims to determine the underlying pathophysiological mechanisms and genetic basis for CVS, as well as identifying potential biomarkers for the disorder. Soliciting government and industry support is crucial to establishing the necessary infrastructure and achieving these goals. Patient advocacy groups such as the Cyclic Vomiting Syndrome Association (CVSA), which partner with clinicians and researchers to disseminate new information, to promote ongoing interactions between patients, their families, clinicians, investigators, to support ongoing CVS research and education, must be an integral part of this endeavor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/1/nmo13607.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/2/nmo13607_am.pd

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence‐based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate‐to‐severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first‐line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L‐carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well‐being and patient care outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/1/nmo13604.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/2/nmo13604_am.pd

Management of cyclic vomiting syndrome in adults: Evidence review

BackgroundThis evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults.MethodsWe followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant?ResultsWe found very low‐quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co‐morbid conditions and complementary therapies.ConclusionsThis evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/1/nmo13605.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/2/nmo13605_am.pd

WDM for Multi-user Indoor VLC Systems with SCM

A system that employs wavelength division multiplexing (WDM) in conjunction with subcarrier multiplexing (SCM) tones is proposed to realize high data rate multi-user indoor visible light communication (VLC). The SCM tones, which are unmodulated signals, are used to identify each light unit, to find the optimum light unit for each user and to calculate the level of the co-channel interference (CCI). WDM is utilized to attain a high data rate for each user. In this paper, multicolour (four colours) laser diodes (LDs) are utilized as sources of lighting and data communication. One of the WDM colours is used to convey the SCM tones at the beginning of the connection to set up the connection among receivers and light units (to find the optimum light unit for each user). To evaluate the performance of our VLC system, we propose two types of receivers: an array of non-imaging receivers (NI-R) and an array of non-imaging angle diversity receivers (NI-ADR). In this paper, we consider the effects of diffuse reflections, CCI and mobility on the system performance

Pulse laser ablated growth of Au-Ag nanocolloids: basic insight on physiochemical attributes

Despite considerable research the evidence around the wide applications in the nanomedicine and nanophotonic area of gold-silver (Au-Ag) nanocolloids remains equivocal and under exploration. Due to their physical properties, enhanced permeability, high fluorescent, surface area to volume ratio, retention effect, localized surface plasmon resonance (LSPR) and controlled perfusion of drugs, made Au-Ag nanoparticles is over interested. Hence, we produced Au-Ag nanocolloids using nanosecond pulse laser ablation in liquid (NPLAL) technique. Targets of Au and Ag were submerged individually inside the cubic vessel fulfilled by 8 mL of glycol liquid media and vertically ablated with different pulse laser ablation (PLA) energy (50, 100, 150 and 200 mJ). The influence of the PLA energy (at fundamental wavelength 1064 nm) on the optical properties, morphology, particle size distribution, and chemical structure of the obtained colloidal Au-Au NPs was established. UV-Vis and FTIR spectrophotometers have been utilized to determine the absorbance characteristics and chemical functional groups of Au-Ag nanostructures, respectively. The attained of Au-Ag nanostructure exhibits a single-surface plasmon resonance (SPR) band, positioned between SPR bands of the monometallic and a surface bonding functional group (e.g. carboxyl or hydroxy groups). The proposed technique can be a basis for the developing complex compositions/colloids with unique and optimal physical properties may use for developing future nanomedicinal and nanophotonics

Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome

Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called “compulsive hot water bathing” has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow‐up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/1/nmo13606_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/2/nmo13606.pd