Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics.

Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity-dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities, and enhancing NAD biosynthesis permits the expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) could predict division potential for both T and B cells, before the first division, unmixing proliferative heterogeneity. We believe that this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.

Enhancing Psychiatry Education through Podcasting: Learning from the Listener Experience.

OBJECTIVE: Podcasts have recently been introduced into psychiatry education, despite limited evidence evaluating podcasting in medical education. PsychEd is an educational, publicly available podcast targeting junior learners in psychiatry. This study characterized PsychEd's listeners and the podcast's role in their education. METHODS: The study involved a mixed-methods survey, followed by semi-structured phone interviews with respondents. There were 97 survey responders in total, of whom 9 participated in a telephone interview. Survey responses were coded as interval data and analyzed descriptively using statistical software. Interviews were transcribed and coded for emergent themes using a grounded theory model. RESULTS: PsychEd listeners represented an interprofessional audience, with 46 respondents (48%) being physicians or physicians in training, and 34 (35%) being allied mental health professionals. All respondents (100%) rated the podcast as "helpful" or "very helpful" for general knowledge. Listeners were attracted to PsychEd for the auditory learning format, the opportunity to review existing knowledge, the focus on core topics, the Canadian expertise, and the presentation of "clinical pearls." Respondents highlighted valuable qualities of a psychiatry podcast: conversational, case-based, narrative approach, longer episodes (i.e., 30-60 minutes) as compared to other medical specialties, and a clinical focus. Furthermore, they identified podcasts as an opportunity for shared interprofessional curricula. CONCLUSION: This study is the first to examine the motivations and experiences of listeners of a psychiatry educational podcast. The findings support existing literature on the benefits of podcasts in medical education. Future studies should explore the impact of podcasts on learning and behaviors.

Development and uncertainty characterization of 3D particle location from perspective shifted plenoptic images.

This work details the development of an algorithm to determine 3D position and in plane size and shape of particles by exploiting the perspective shift capabilities of a plenoptic camera combined with stereo-matching methods. This algorithm is validated using an experimental data set previously examined in a refocusing based particle location study in which a static particle field is translated to provide known depth displacements at varied magnification and object distances. Examination of these results indicates increased accuracy and precision is achieved compared to a previous refocusing based method at significantly reduced computational costs. The perspective shift method is further applied to fragment localization and sizing in a lab scale fragmenting explosive.

Volumetric calibration of a plenoptic camera.

The volumetric calibration of a plenoptic camera is explored to correct for inaccuracies due to real-world lens distortions and thin-lens assumptions in current processing methods. Two methods of volumetric calibration based on a polynomial mapping function that does not require knowledge of specific lens parameters are presented and compared to a calibration based on thin-lens assumptions. The first method, volumetric dewarping, is executed by creation of a volumetric representation of a scene using the thin-lens assumptions, which is then corrected in post-processing using a polynomial mapping function. The second method, direct light-field calibration, uses the polynomial mapping in creation of the initial volumetric representation to relate locations in object space directly to image sensor locations. The accuracy and feasibility of these methods is examined experimentally by capturing images of a known dot card at a variety of depths. Results suggest that use of a 3D polynomial mapping function provides a significant increase in reconstruction accuracy and that the achievable accuracy is similar using either polynomial-mapping-based method. Additionally, direct light-field calibration provides significant computational benefits by eliminating some intermediate processing steps found in other methods. Finally, the flexibility of this method is shown for a nonplanar calibration.

Uncertainty characterization of particle location from refocused plenoptic images.

Plenoptic imaging is a 3D imaging technique that has been applied for quantification of 3D particle locations and sizes. This work experimentally evaluates the accuracy and precision of such measurements by investigating a static particle field translated to known displacements. Measured 3D displacement values are determined from sharpness metrics applied to volumetric representations of the particle field created using refocused plenoptic images, corrected using a recently developed calibration technique. Comparison of measured and known displacements for many thousands of particles allows for evaluation of measurement uncertainty. Mean displacement error, as a measure of accuracy, is shown to agree with predicted spatial resolution over the entire measurement domain, indicating robustness of the calibration methods. On the other hand, variation in the error, as a measure of precision, fluctuates as a function of particle depth in the optical direction. Error shows the smallest variation within the predicted depth of field of the plenoptic camera, with a gradual increase outside this range. The quantitative uncertainty values provided here can guide future measurement optimization and will serve as useful metrics for design of improved processing algorithms.

Comparison of three-dimensional particle tracking and sizing using plenoptic imaging and digital in-line holography.

Digital in-line holography (DIH) and plenoptic photography are two techniques for single-shot, volumetric measurement of 3D particle fields. Here we present a comparison of the two methods by applying plenoptic imaging to experimental configurations that have been previously investigated with DIH. These experiments include the tracking of secondary droplets from the impact of a water drop on a thin film of water and tracking of pellets from a shotgun. Both plenoptic imaging and DIH successfully quantify the 3D nature of these particle fields. This includes measurement of the 3D particle position, individual particle sizes, and three-component velocity vectors. For the initial processing methods presented here, both techniques give out-of-plane positional accuracy of approximately 1-2 particle diameters. For a fixed image sensor, digital holography achieves higher effective in-plane spatial resolutions. However, collimated and coherent illumination makes holography susceptible to image distortion through index of refraction gradients, as demonstrated in the shotgun experiments. In contrast, plenoptic imaging allows for a simpler experimental configuration and, due to the use of diffuse, white-light illumination, plenoptic imaging is less susceptible to image distortion in the shotgun experiments.

A case of a probable drug interaction between lurasidone and atazanavir-based antiretroviral therapy.

The cytochrome P450 isoform that is primarily involved in the metabolism of the antipsychotic lurasidone is CYP3A4. Drugs that inhibit or induce this enzyme would then be expected to increase or decrease serum concentrations of lurasidone, respectively. Atazanavir, an HIV-1 protease inhibitor, has demonstrated to be an inhibitor of CYP3A4 and would be expected to increase the exposure of any drug metabolized by this enzyme. We report a case of an atazanavir-precipitated drug-drug interaction that led to elevated serum concentrations of lurasidone and associated clinical symptoms of drug toxicity.

Electrochemical bromination of organosulfur containing species for the determination of the strength of garlic (A. sativum).

The extraction by ethyl acetate and subsequent electrochemical detection of organosulfur containing molecules from garlic is demonstrated. The electrochemical results first evidence the high sensitivity of the process towards the model compound propyl disulfide. Through the in situ formation of bromine at a platinum electrode the propyl disulfide can be readily detected at concentrations as low as 12.5 µM. Second, the work focuses on the detection of organosulfur from fresh garlic samples. Extraction of the organosulfur 'flavour' molecules is achieved with ethyl acetate. Addition of this extract to the electrochemical cell results in an analytically useful signal allowing the voltammetric peak height to be successfully correlated with the garlic strength, as measured using an organoleptic tasting panel.

Psychiatric symptoms and disorders associated with reproductive cyclicity in women: advances in screening tools.

Female-specific psychiatric illness including premenstrual dysphoria, perinatal depression, and psychopathology related to the perimenopausal period are often underdiagnosed and treated. These conditions can negatively affect the quality of life for women and their families. The development of screening tools has helped guide our understanding of these conditions. There is a wide disparity in the methods, definitions, and tools used in studies relevant to female-specific psychiatric illness. As a result, there is no consensus on one tool that is most appropriate for use in a research or clinical setting. In reviewing this topic, we hope to highlight the evolution of various tools as they have built on preexisting instruments and to identify the psychometric properties and clinical applicability of available tools. It would be valuable for researchers to reach a consensus on a core set of screening instruments specific to female psychopathology to gain consistency within and between clinical settings.

Serotonin and female psychopathology.

There are sex differences in the prevalence and presentation of many psychiatric disorders. Various trends in symptomatology have emerged that are thought to be linked to periods of hormonal fluctuations such as with menses, pregnancy or menopause. With data from animal and human studies, it has become clear that there is an important interplay between the serotonergic system and gonadal hormones. The majority of the research to date has focused on the influence that estrogen has within the CNS and, in particular, how it leads to an overall increase in serotonin synthesis and availability. In reviewing this female-specific topic we hope to raise awareness to sex/gender differences in psychopathology, help identify at-risk populations and consider development of new treatment options. Future research will also need to consider the influence that progesterone and oxytocin may have on sex-specific psychopathology as well as incorporate neuroimaging and consider the influence of hormones on the serotonergic system at a genetic level.

Male fertility: psychiatric considerations.

OBJECTIVE: To examine: 1) current knowledge on normal biologic variation of seminal parameters; 2) how stress and psychological factors affect sperm quality in fertile and infertile males; and 3) how mental illness and psychopharmacologic agents can affect male fertility. DESIGN: English-language Medline, Embase, and Psycinfo were searched for relevant publications (from 1970 to January 2011) for systematic review. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Possible effects of stress, mood, and psychotropic medications on male factor fertility. RESULT(S): Male-factor infertility is influenced by myriad factors (obesity, tobacco, etc.). Stress alone may reduce testosterone levels and spermatogenesis. Infertility assessment and treatment can lead to distress and negatively affect sperm samples. Available research has failed to control for potentially confounding variables. CONCLUSION(S): Although some trends have been identified, larger-scale studies that adequately control all confounding variables are needed before conclusions can be made about the relationship between stress, psychotropic agents, and male infertility.

Non-hormonal treatment strategies for vasomotor symptoms: a critical review.

Hot flashes (or flushes) are the most commonly reported symptoms during the menopause transition and early postmenopausal years, particularly in Western societies; they affect 60-90% of women and can lead to significant physical discomfort and functional impairment. The emergence of hot flashes and night sweats (also known as vasomotor symptoms [VMS]) coincide with a period in life that is also marked by dynamic changes in hormone and reproductive function that interconnect with the aging process, changes in metabolism, lifestyle behaviours and overall health. Estrogen-based therapies have long been the treatment of choice for women suffering from VMS. More recent concerns over long-term safety of menopausal hormone treatments, however, have led physicians and patients to pursue non-hormonal strategies to alleviate their symptoms. In this article, we review most of the efficacy and safety data on non-hormonal treatments for VMS published over the past 20 years. We discuss the evidence for treating symptomatic women in different clinical scenarios, e.g. VMS with and without concomitant depression or VMS following the use of anti-estrogen therapies. Overall, efficacy data support the use of some psychotropic medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and gabapentin. Complementary and alternative methods for VMS also showed limited but promising results, although more definitive studies are warranted. Clinicians should therefore be able to tailor treatment strategies for those who are unable or unwilling to use hormones to alleviate VMS and improve overall functioning and quality of life.