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BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD.

Magnetic resonance imaging (MRI) was used to monitor internal changes in harvested tomato (Solanum lycopersicum L. cv. Micro-Tom) fruit. Measurements of ethylene evolution, respiration, and ion leakage indicated that the fruit developed chilling injury (CI) after storage at 0. °C. Unlike these measurements, MRI provided spatially resolved data. The apparent diffusion coefficient (ADC), which is an indication of water mobility in tissues, was calculated from MRIs of the different parts of the fruit. Storage for 1 or 2 weeks at 0. °C caused no difference in the ADCs (D-values) in the pericarp, but it did lead to higher values in the inner tissues i.e., the columella and locular region compared to non-chilled fruit (P< 0.05). Changes in inner fruit D-values after 1 and 2 weeks of chilling at 0. °C were similar to changes in respiration, ethylene production and ion leakage which increased (P< 0.05) compared to the non-chilled controls. Most CI studies of tomato fruit used pericarp tissue. Our data indicate that columella tissue changes occur in response to chilling injury in tomato fruit and suggest that more caution is needed when interpreting data from experiments commonly used to study this phenomenon. © 2014 Elsevier B.V.

Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

An association between circadian clock function and mood regulation is well established and has been proposed as a factor in the development of mood disorders. Patients with depression or mania suffer disturbed sleep-wake cycles and altered rhythms in daily activities. Environmentally disrupted circadian rhythms increase the risk of mood disorders in the general population. However, proof that a disturbance of circadian rhythms is causally involved in the development of psychiatric disorders remains elusive. Using clock gene mutants, manipulations of sleep-wake and light-dark cycles, and brain lesions affecting clock function, animal models have been developed to investigate whether circadian rhythm disruptions alter mood. In this review, selected animal models are examined to address the issue of causality between circadian rhythms and affective behavior.

Carbenes are reactive molecules of the form R(1)-:C-R(2) that play a role in topics ranging from organic synthesis to gas-phase oxidation chemistry. We report the first experimental structure determination of dihydroxycarbene (HO-:C-OH), one of the smallest stable singlet carbenes, using a combination of microwave rotational spectroscopy and high-level coupled-cluster calculations. The semi-experimental equilibrium structure derived from five isotopic variants of HO-:C-OH contains two very short CO single bonds (ca. 1.32 Å). Detection of HO-:C-OH in the gas phase firmly establishes that it is stable to isomerization, yet it has been underrepresented in discussions of the CH2O2 chemical system and its atmospherically relevant isomers: formic acid and the Criegee intermediate CH2OO.

Nuclear magnetic resonance (NMR) spectroscopy is used to track factory relevant tomato paste spoilage. It was found that spoilage in tomato paste test samples leads to longer spin lattice relaxation times T1 using a conventional low magnetic field NMR system. The increase in T1 value for contaminated samples over a five day room temperature exposure period prompted the work to be extended to the study of industry standard, 1,000 L, non-ferrous, metal-lined totes. NMR signals and T1 values were recovered from a large format container with a single-sided NMR sensor. The results of this work suggest that a handheld NMR device can be used to study tomato paste spoilage in factory process environments.

The article presents the discussion on keynote speech by the then Secretary of Health, Education and Welfare. Topics include range of social movements arrayed in opposition to colonialism, poverty, and racism mobilized during the Democratic Convention in Chicago to protest; and taking the initiative by planning workshops and social actions to unsettle the discipline's establishment sociology.

Study Design: Retrospective cohort study Objective: Given changes in bone density induced by degenerative disease, general measures of bone health (ie DEXA) are inadequate to evaluate bone density in surgical areas of interest. Regional differences in HU in the cervical spine may influence surgical strategies. The purposes of our study were to determine whether cervical Hounsfield units (HU) vary by level, examine their relationship with age, comorbidities, and alignment, and propose a technique to measure HU in the lateral masses. Methods: Two hundred twenty-four patients with degenerative spine pathology with a cervical computed tomography were included (2015-2019). Measurements were performed in each vertebral body (C2-T1; mid-axial, anterior-axial, posterior-axial, mid-coronal, and mid-sagittal) and 2 regions of the lateral masses (C3-C6; mid-cor, mid-sag). To evaluate reliability, 6 observers each measured 355 HU values, inter-relater reliability assessed with intraclass correlation coefficients Correlations of HU with age, BMI, comorbidities, and cervical alignment were evaluated. Results: Bone density differed by level, with the lowest HU scores in the lower cervical spine (C6-T1) (P <.001). No correlations were found between LM HU and age, BMI, CCI, or alignment (P >.05). Increased kyphosis was weakly correlated with VB HU, while age and CCI showed moderate correlations with VB HU at all levels (P<.001). ICC for HU measurements were good to excellent for the VBs, but poor to moderate for the LMs. Conclusion: Bone is least dense in the lower cervical spine. HU scoring is not reliable in the lateral masses. We recommend that a level-specific approach to bone density is considered in surgical planning. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Objectives: Identify optimal lumbar lordosis in adult deformity correction to achieve age-adjusted targets and sustained alignment. Methods: Surgical adult spinal deformity patients reaching an age-adjusted ideal alignment at one year were identified. Multilinear regression analysis was used to identify the relationship between regional curvatures (LL and TK) that enabled achievement of a given global alignment (T1 pelvic angle, TPA) based on pelvic incidence (PI). Results: 347 patients out of 1048 available reached their age-adjusted TPA within 5° (60-year-old, 72% women, body mass index 29 ± 6.2). They had a significant improvement in all sagittal parameters (except PI) from pre-operative baseline to 1 year following surgery (P <.001). Multilinear regression predicting L1-S1 based on TK, TPA, and PI demonstrated excellent results (R2 =.85). Simplification of the coefficients of prediction combined with a conversion to an age-based formula led to the following: LL = PI - 0.3TK - 0.5Age + 10. Internal validation of the formula led to a mean error of −.4°, and an absolute error of 5.0°. Internal validation on patients with an age-adjusted alignment revealed similar accuracy across the entire age-adjusted TPA spectrum (ranges of LL errors: ME =.2° to 1.7°, AE = 4.0° to 5.3°). Conclusion: This study provides a simple guideline to identify the amount of LL needed to reach a given alignment (i.e., age-adjusted target) based on PI and associated TK. Implementation of this predictive formula during pre-operative surgical planning may help to reduce unexpected sub-optimal post-operative alignment outcomes. [ABSTRACT FROM AUTHOR]