Irritability and emotional dysregulation are challenging symptoms to treat in individuals with autism spectrum disorders (ASD). Thankfully, there are several multimodal treatment approaches for which ...there is some empirical evidence, with the number of emerging pharmacological options growing every day. Although much progress has been made in the overall treatment of ASD, the field has eluded innovating on treatments that definitively improve irritability and emotional dysregulation without also causing untoward side effects. Sampling biases, underpowered studies, and measurement problems are challenges that are also opportunities to iterate toward better and more personalized treatments. This editorial reviews the metanalytic syntheses of extant pharmacological options to target irritability and emotional dysregulation in ASD, providing some perspectives about the impact of the current limits of our knowledge, and attempts to conclude hopefully with a horizon of many promising directions for future research.
Cultivating Hope Singh, Manpreet K
JAMA : the journal of the American Medical Association,
05/2020, Volume:
323, Issue:
18
Journal Article
Peer reviewed
In this narrative medicine essay, a pediatric psychiatrist relates how her younger sister with Down syndrome and congenital heart disease has lived well beyond expectation inspired her to help ...children cultivate hope through love and resilience.
Tuberculosis (TB) remains an eminent global burden with one third of the world's population latently infected with Mycobacterium tuberculosis (M. tb). Individuals with compromised immune systems are ...especially vulnerable to M. tb infection. In fact, individuals with Type 2 Diabetes Mellitus (T2DM) are two to three times more susceptible to TB than those without T2DM. In this study, we report that individuals with T2DM have lower levels of glutathione (GSH) due to compromised levels of GSH synthesis and metabolism enzymes. Transforming growth factor beta (TGF-β), a cytokine that is known to decrease the expression of the catalytic subunit of glutamine-cysteine ligase (GCLC) was found in increased levels in the plasma samples from individuals with T2DM, explaining the possible underlying mechanism that is responsible for decreased levels of GSH in individuals with T2DM. Moreover, increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-17 (IL-17) were observed in plasma samples isolated from individuals with T2DM. Increased levels of IL-6 and IL-17 was accompanied by enhanced production of free radicals further indicating an alternative mechanism for the decreased levels of GSH in individuals with T2DM. Augmenting the levels of GSH in macrophages isolated from individuals with T2DM resulted in improved control of M. tb infection. Furthermore, cytokines that are responsible for controlling M. tb infection at the cellular and granuloma level such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), were found to be compromised in plasma samples isolated from individuals with T2DM. On the other hand, interleukin-10 (IL-10), an immunosuppressive cytokine was increased in plasma samples isolated from individuals with T2DM. Overall, these findings suggest that lower levels of GSH in individuals with T2DM lead to their increased susceptibility to M. tb infection.
Development of antibiotic resistance in foodborne pathogens, Salmonella spp. and Campylobacter, is a public health concern. Public demand to reduce the use of sub-therapeutic antibiotic growth ...promoters (AGP) in poultry feeding has resulted in greater adoption of antibiotic-free poultry production systems. There is a need to understand the effects of AGP removal from poultry feed on gut microbiota and its impact on prevalence of foodborne pathogens. The effect of antibiotic withdrawal from poultry feed on gut microbial community, host performance and immunity, and prevalence of Salmonella and Campylobacter was evaluated. Birds were raised on three phase diets (starter d0-22, grower d23-35 and finisher d36-42) with and without bacitracin dimethyl salicyclate (BMD). At early growth stage, bird performance was improved (P ≤ 0.05) with BMD treatment, whereas performance was better (P ≤ 0.05) in control group (no BMD in the feed) at the time of commercial processing. Acetate and butyrate production was affected (P ≤ 0.05) by age, whereas propionate production was affected (P ≤ 0.05) by both the treatment and age. The bacterial communities in the cecum were more diverse (P ≤ 0.001) and rich compared to the ileal communities, and they shifted in parallel to one another as the chicks matured. Differences in diversity and species richness were not observed (P > 0.05) between the BMD-fed and control groups. Comparing all ages, treatments and diets, the composition of cecal and ileal bacterial communities was different (P ≤ 0.001). Inclusion of BMD in the feed did not affect the bacterial phyla. However, predictable shift in the ileal and cecal bacterial population at lower taxonomic level was observed in control vs BMD-fed group. Cytokines gene expression (IL-10, IL-4, IFN-γ, beta-defensin, and TLR-4) was affected (P≤ 0.05) in the BMD-fed group at early stages of growth. The prevalence of foodborne pathogens, Campylobacter spp. and Salmonella spp. showed higher abundance in the ilea of BMD-fed chicks compared to control group. Overall, this study provided insight of the impact of AGP supplementation in the feed on gut microbial modulations, bird performance, host immunity and pathogen prevalence. This information can assist in designing alternative strategies to replace antibiotics in modern poultry production and for food safety.
Physical Classification of ripe fruits is an expensive affair in the agriculture industry and human error can lead to inaccurate results. This paper introduces the concept of an intelligent AI-based ...system using spectrophotometry and computer vision for automated fruit segregation based on their grade. When the fruit is fed into the proposed system, the fruit is identified with 95% accuracy, using a cloud-computing platform provided by Microsoft Azure. After that, using spectroscopy and ensemble machine learning approaches, fruit grade is predicted. This ensemble model is trained using 1366 apple readings taken from Unitec's Apple Sorting and Grading Machine from an industrial plant. With the help of H2O's Driverless.AI, the proposed ensemble provides an overall approximate validation accuracy of 82%. The model is also tested on an unseen test dataset containing real-life spectral values and the accuracy of fruit segregation into different classes peaked at 72%.
Abstract
Over the last few decades, different types of plasma waves (e.g., the ion acoustic waves (IAWs), electrostatic solitary waves, upper/lower hybrid waves, and Langmuir waves) have been ...observed in the upstream, downstream, and ramp regions of the collisionless interplanetary (IP) shocks. These waves may appear as short-duration (only a few milliseconds at 1 au) electric field signatures in the in-situ measurements, with typical frequencies of ∼1–10 kHz. A number of IAW features at the IP shocks seem to be unexplained by kinetic models and require a new modeling effort. Thus, this paper is dedicated to bridging this gap in understanding. In this paper, we model the linear IAWs inside the shock ramp by devising a novel linearization method for the two-fluid magnetohydrodynamic equations with spatially dependent shock parameters. It is found that, for parallel propagating waves, the linear dispersion relation leads to a finite growth rate, which is dependent on the shock density compression ratio, as Wind data suggest. Further analysis reveals that the wave frequency grows towards the downstream region within the shock ramp, and the wave growth rate is independent of the electron-to-ion temperature ratio, as Magnetospheric Multiscale (MMS) in-situ measurements suggest, and is uniform within the shock ramp. Thus, this study helps in understanding the characteristics of the IAWs at the collisionless IP shocks.
Comorbidity in mental disorders is prevalent among adolescents, with evidence suggesting a general psychopathology factor (“p” factor) that reflects shared mechanisms across different disorders. ...However, the association between the “p” factor and protective factors remains understudied. The current study aimed to explore the “p” factor, and its associations with psycho-social functioning, in Chinese adolescents.
2052 students, aged 9–17, were recruited from primary and secondary schools in Shanghai, China. Multiple rating scales were used to assess psychological symptoms and psycho-social functioning. Confirmatory factor analysis was conducted to verify the fit of models involving different psychopathology domains such as externalizing, internalizing, and the “p” factor. Subsequently, structural equation models were used to explore associations between the extracted factors and psycho-social functioning, including emotion regulation, mindful attention awareness, self-esteem, self-efficacy, resilience, and perceived support.
The bi-factor model demonstrated a good fit, with a “p” factor accounting for 46 % of symptom variation, indicating that the psychological symptoms of Chinese adolescents could be explained by internalizing, externalizing, and the “p” factor. Psychologically, a higher “p” was positively correlated with emotion suppression and negatively correlated with mindful attention awareness, emotion reappraisal, self-esteem, and resilience. Socially, a higher “p” was associated with decreased perceived support.
Only common symptoms were included as this study was conducted at school. Furthermore, the cross-sectional design limited our ability to investigate causal relationships.
A “p” factor exists among Chinese adolescents. Individuals with higher “p” factor levels were prone to experience lower levels of psycho-social functions.
•This study aimed to explore the "p" factor and its associations with psycho-social functioning in Chinese adolescents.•The psychological symptoms of Chinese adolescents could be explained by internalizing, externalizing, and the "p" factor.•Individuals with higher "p" factor levels were prone to experiencing lower psycho-social functioning.•This study highlights the "p" factor's role in protective factors and identifies variables for trans-diagnostic interventions.
Depression is a serious and persistent psychiatric disorder that commonly first manifests during childhood. Depression that starts in childhood is increasing in frequency, likely due both to ...evolutionary trends and to increased recognition of the disorder. In this umbrella review, we systematically searched the extant literature for genetic, epigenetic, and neurobiological factors that contribute to a childhood onset of depression. We searched PubMed, EMBASE, OVID/PsychInfo, and Google Scholar with the following inclusion criteria: (1) systematic review or meta-analysis from a peer-reviewed journal; (2) inclusion of a measure assessing early age of onset of depression; and (3) assessment of neurobiological, genetic, environmental, and epigenetic predictors of early onset depression. Findings from 89 systematic reviews of moderate to high quality suggest that childhood-onset depressive disorders have neurobiological, genetic, environmental, and epigenetic roots consistent with a diathesis-stress theory of depression. This review identified key putative markers that may be targeted for personalized clinical decision-making and provide important insights concerning candidate mechanisms that might underpin the early onset of depression.
•Heterogeneous blood perfusion mapping in spatial coordinates, ωb(x,y,z) using medical imaging.•Modified Pennes bioheat equation.•High perfusion, moderate perfusion, low perfusion, no ...perfusion.•Spatially varying blood perfusion term.
The Pennes bioheat equation is a widely used mathematical model for predicting temperature distribution in biological tissues. However, it assumes homogeneous blood perfusion throughout the tissue, which may not accurately represent the complex perfusion patterns observed in tumors. In this study, we propose modification to traditional Pennes bioheat equation that incorporates the effects of perfusion heterogeneity by introducing a spatially varying perfusion term, represented by a perfusion coefficient, ωb(x,y,z) to account for local variations in blood flow at each spatial location within the biological tissue. Therefore, heterogeneous blood perfusion at each tumor tissue voxel location relax the uniform blood perfusion assumption. By incorporating these modifications, the model allows for a more realistic representation of the heat exchange between the biological tissue and blood flow, by predicting the non-uniform temperature distribution particularly in tumors with irregular blood vessel growth and organization, thereby facilitating treatment planning and optimization of thermal therapies, and leading to more effective therapeutic outcomes. The spatially varying perfusion coefficient can be obtained through advanced imaging techniques such as dynamic contrast-enhanced MRI or Doppler ultrasound enabling the assessment of perfusion heterogeneity in biological tissues. In conclusion, the modified Pennes bioheat equation offers a valuable tool for understanding the intricate relationship between with heterogeneous blood perfusion and temperature distribution in biological tissues, providing important insights to the thermal response of tumors and guiding the development of improved therapeutic strategies in optimizing cancer treatments.
Heterogeneous blood perfusion, ωb(x,y,z) source map of image-extracted PC3 tumor anatomy in axial plane (X-Y), sagittal plane (Y-Z), coronal plane (X-Z), three-dimensional view (X-Y-Z) is shown. Spatial coordinates are mapped with Eucledian distance approach. The color gradient shows the resulting perfusion at each tumor tissue location (red is high, blue is low). The UBF (uniform tumor blood flow), represents an easy-to-heat perfusion pattern with uniform perfusion demarcation at meshing coordinates, ABF (annular tumor blood flow), refers to hard-to-heat perfusion pattern with annular rings one inside another, RBF (randomized tumor blood flow) possess regions of no perfusion (NP) referred to as central dead-necrotic core (NC) region free from potential blood vessels, high perfusion (HP) at tumor peripheral region (PR), low perfusion (LP) and moderate perfusion (MP) at intermediate regions (IR). The color gradient shows the resulting perfusion at each tumor tissue location (red is high, blue is low). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Display omitted
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