Blood-brain barrier dysfunction in bipolar disorder: Molecular mechanisms and clinical implications.

Bipolar disorder (BD) is a severe psychiatric disorder affecting approximately 1-3% of the population and characterized by a chronic and recurrent course of debilitating symptoms. An increasing focus has been directed to discover and explain the function of Blood-Brain Barrier (BBB) integrity and its association with a number of psychiatric disorders; however, there has been limited research in the role of BBB integrity in BD. Multiple pathways may play crucial roles in modulating BBB integrity in BD, such as inflammation, insulin resistance, and alterations of neuronal plasticity. In turn, BBB impairment is hypothesized to have a significant clinical impact in BD patients. Based on the high prevalence of medical and psychiatric comorbidities in BD and a growing body of evidence linking inflammatory and neuroinflammatory mechanisms to the disorder, recent studies have suggested that BBB dysfunction may play a key role in BD's pathophysiology. In this comprehensive narrative review, we aim to discuss studies investigating biological markers of BBB in patients with BD, mechanisms that modulate BBB integrity, their clinical implications on patients, and key targets for future development of novel therapies.

Association between the CLOCK gene polymorphism and depressive symptom mediated by sleep quality among non-clinical Chinese Han population.

BACKGROUND: Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs). METHODS: Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality, the Zung's Self-rating Depression Scale (SDS) to measure depressive symptom, and the Work Stress Scale to measure job stress. The CLOCK gene rs12649507 polymorphism was genotyped in 289 blood samples. RESULTS: There were positive inter-correlations between job stress, PSQI and SDS (almost ps < 0.05). GG homozygotes of the SNP had higher PSQI and its sleep duration and daytime dysfunction scores than AA homozygotes (all Bonferroni corrected ps0.05). The SNP had no main effect on the SDS and did not interact with job stress to affect SDS, PSQI and its dimensions (all ps > 0.05). Interestingly, after controlling for job stress and covariates, the significant effect size of the SNP on the SDS mediated by the PSQI was 0.68 (95% CI [0.24, 1.35]). LIMITATIONS: Some limitations included single professional background, cross-sectional study design, small sample size and potential confounding factors, which could be amended by future research. CONCLUSIONS: Non-clinical Chinese carrying CLOCK gene rs12649507 G-allele may lead to poor sleep quality and further depression symptoms.

Mini-review: The anti-aging effects of lithium in bipolar disorder.

The medical use of lithium has grown since its initial introduction in the 1800s as a treatment for gout. Today, the divalent cation remains as the pharmacological gold standard in treatment of bipolar disorder (BD) with strong mood stabilizing effects. Lithium has demonstrated efficacy in the treatment of acute affective episodes, in the reduction of affective episode recurrence, and in significantly decreasing the risk of suicide in patients. BD has been consistently associated with clinical signs of accelerated aging, including increased rates of age-related diseases such as cardiovascular diseases, malignancies, and diabetes mellitus. This clinical scenario parallels accelerated aging mechanisms observed on a molecular basis, with studies reporting shortened telomeres, increased oxidative stress, and accelerated epigenetic aging in patients with BD compared to controls. Lithium has proved useful as a potential agent in slowing down this accelerated aging process in BD, potentially reversing effects induced by the disorder. This mini-review summarizes findings of anti-aging mechanisms associated with lithium use and provides a discussion of the clinical implications and perspectives of this evolving field. Despite many promising results, more studies are warranted in order to elucidate the exact mechanism by which lithium may act as an anti-aging agent and the extent to which these mechanisms are relevant to its mood stabilizing properties in BD.

Characteristics and Survival Outcomes of Second Primary Cancers in Long-term Retinoblastoma Survivors.

PURPOSE: Retinoblastoma (RB) is the most common intraocular cancer and is associated with lifelong risks of developing a second primary cancer, especially in patients with hereditary RB and/or childhood exposure to radiotherapy. METHODS: The study included all consecutive patients with a history of RB treated for a second primary cancer during 1994-2018. Patient demographics and characteristics of the primary RB and second primary cancer were examined. The associations among radiation or chemotherapy exposure as a treatment for RB, unilateral versus bilateral status, types and multiplicity of second primary cancers, and survival after diagnosis of second primary cancer were analyzed. RESULTS: A wide spectrum of second primary cancer types was identified from 62 eligible patients (30 males and 32 females), including sarcoma, breast cancer, various skin cancers, gastrointestinal and genitourinary cancers, and endocrine cancers. Of all patients who had second primary cancers, 40 patients (65%) had bilateral RB and 17 patients (27%) had unilateral RB. Thirty-five patients (56%) who developed second primary cancers received radiation therapy during childhood as the treatment of RB, and 17 patients (27%) received chemotherapy for the treatment of RB. The 5-year and 10-year survival rates for RB patients diagnosed with a second primary cancer were 54.0% and 36.0%, respectively. The median age of onset of second primary cancer among RB survivors was 36.6 years. CONCLUSIONS: In contrast to previous studies, we found a broader spectrum of second primary cancer types. All RB survivors, regardless of unilateral or bilateral status, should undergo strict cancer surveillance particularly as they approach the fourth decade of life.

Use Your Noodle to Simulate Tourniquet Use on a Limb With and Without Bone.

BACKGROUND: The purpose of this study was to simulate first aid by mechanical use of a limb tourniquet on a thigh with and without bone to better understand best caregiving practices. METHODS: Two investigators studied simulated first aid on a new pool "noodle," a plastic cylinder with a central air tunnel into which we inserted a wood dowel to simulate bone. Data were gathered by group (study and control, n = 12 each). The control group comprised data collected from simulated tourniquet use on the model with bone present. The study group comprised data from simulated tourniquet use on the model without bone. RESULTS: Comparing compression with and without bone, the mean volumes of compressed soft tissues alone were 303mL and 306mL, respectively. When bone was present, the volume of soft tissues was squeezed more, yielding a smaller size by 3mL (1%). The bone had a volume of 41mL and pressed statically outward with an equal force oppositely directed to the inward compression of the overlying soft tissues. With bone removed and compression applied, the mean residual void was 16mL, because 25mL (i.e., 41mL minus 16mL) of soft tissues had collapsed inward. The volume of the limb under the tourniquet with and without bone was 344mL and 322mL, respectively. The collapse volume, 25mL, was 3mL more than the difference of the mean volume of the limb under the tourniquet. More limb squeeze (22mL) looked like better compression, but it was actually worse-an illusion created by collapse of the hidden void. CONCLUSION: In simulated first aid, mechanical modeling demonstrated how tourniquet compression applied to a limb squeezed the soft tissues better when underlying bone was present. Bone loss altered the compression profile and may complicate control of bleeding in care. This knowledge, its depiction, and its demonstration may inform first-aid instructors.

Your Metric Matters! Choose Wisely to Assess User Performance With Tourniquets in Simulated First Aid.

BACKGROUND: Readiness to perform lifesaving interventions during emergencies is based on a person's preparation to proficiently execute the skills required. Graphically plotting the performance of a tourniquet user in simulation has previously aided us in developing our understanding of how the user actually behaves. The purpose of this study was to explore performance assessment and learning curves to better understand how to develop best teaching practices. METHODS: These were retrospective analyses of a convenience sample of data from a prior manikin study of 200 tourniquet uses among 10 users. We sought to generate hypotheses about performance assessments relevant to developing best teaching practices. The focus was on different metrics of user performance. RESULTS: When one metric was chosen over another, failure counts summed cumulatively over 200 uses differed as much as 12-fold. That difference also indicated that the degree of challenge posed to user performance differed by the metric chosen. When we ranked user performance with one metric and then with another, most (90%; nine of 10) users changed rank: five rose and four fell. Substantial differences in performance outcomes resulted from the difference in metric chosen, which, in turn, changed how the outcome was portrayed and thus interpreted. Hypotheses generated included the following: The usefulness of a specific metric may vary by the user's level of skill from novice to expert; demonstration of the step order in skill performance may suffice for initial training of novices; a mechanical metric of effectiveness, like pulse stoppage, may aid in later training of novices; and training users how to practice on their own and self-assess performance may aid their self-development. CONCLUSION: The outcome of the performance assessments varied depending on the choice of metric in this study of simulated use of tourniquets.