Purpose In a sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer who received at least two cycles of chemotherapy (CTX) the purposes were to: evaluate for inter-individual differences in the severity of sleep disturbance and determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of sleep disturbance. Methods A total of 1,331 patients completed study questionnaires in their homes, at six time points over two cycles of CTX (prior to CTX administration, approximately 1 week after CTX administration, and approximately 2 weeks after CTX administration). Questionnaires included demographic, clinical, and symptom assessments (i.e., General Sleep Disturbance Scale, Lee Fatigue Scale, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventories, Attentional Function Index). Hierarchical linear modeling based on full maximum likelihood estimation was performed. Results Characteristics associated with higher initial levels of sleep disturbance included: higher body mass index, poorer functional status, higher trait anxiety, higher depressive symptoms, and higher evening fatigue. Characteristics associated with the worse trajectories of sleep disturbance were higher levels of education and higher sleep disturbance at enrollment. Characteristics associated with both higher initial levels and worse trajectories of sleep disturbance were higher morning fatigue and worse attentional function. Conclusions A large amount of inter-individual variability exists in sleep disturbance during CTX. The modifiable and non-modifiable characteristics found in this study can be used to identify higher risk patients and provide earlier interventions to reduce sleep disturbance.

Prebeta-1 HDL is a molecular species of plasma HDL of approximately 67 kDa mass that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol. It participates in a cyclic process involved in the retrieval of cholesterol from peripheral tissues. In this cycle, unesterified cholesterol from cells is incorporated into prebeta-1 HDL, providing a substrate for esterification of cholesterol by lecithin:cholesterol acyltransferase. Prebeta-1 HDL then becomes incorporated into larger HDL species of alpha mobility as esterification proceeds and is regenerated during the transfer of cholesteryl esters from alpha HDL particles to acceptor lipoproteins. Thus the steady state level of prebeta-1 HDL in plasma reflects the relative efficiencies of the major metabolic processes involved in its generation and removal. We have used an isotope dilution technique to measure prebeta-1 HDL levels in the plasmas of 136 normolipidemic individuals (46 M, 90 F). The mean absolute concentration of prebeta-1 HDL as apolipoprotein A-I was 68 Ϯ 40 g/ml for women, and 84 Ϯ 49 m/ml for men. Prebeta-1 HDL represented 5.5 Ϯ 3.3% of total apolipoprotein A-I in women, and 7.2 Ϯ 4.0% in men. The distributions of both absolute and percent prebeta-1 HDL are highly asymmetric, with skew toward higher values. However, the skew appears not to be attributable to either plasma cholesterol or triglyceride levels which are also skewed in population samples. The percent prebeta-1 HDL was negatively correlated with HDL cholesterol levels ( P Ͻ 0.0001), whereas absolute levels of prebeta-1 HDL were positively correlated with apolipoprotein A-I and negatively correlated with HDL cholesterol ( P , for both, Ͻ 0.0001). Multiple linear regression analysis revealed effects of age and gender, but no association with lipoprotein fractions other than HDL. Lower levels of prebeta-1 HDL were associated with female gender in all models.

A 39-year-old woman on depot medroxyprogesterone acetate for 17 years developed multiple fractures after falling from a stationary horse. Densitometry revealed significant osteopenia. Although the reported patient was a thin, Caucasian woman, she did not have any other significant risk factors for osteoporosis except for a possible state of partial estrogen deficiency induced by the use of depot medroxyprogesterone acetate. Studies have shown that the estradiol levels of premenopausal women who have received this hormonal contraceptive for more than 1 year never reach those seen in the mid-cycle or luteal phase of the normal menstrual cycle. The estradiol levels are comparable only with those found in the early follicular phase. Therefore, women who use depot medroxyprogesterone acetate are in a state of partial estrogen deficiency, which may be associated with increased bone loss.

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler’s group explored histone Arg (R) methylation in reward processing models. Damez-Werno et al. (2016) reported that during investigator and selfadministration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking. Hypothesis: Hypothesizing that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Discussion: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, results in histone H3 glutamine 5 dopaminylation (H3Q5dop), and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase sig-naling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a “homeostatic brake.” Conclusion: The decrease in Src signaling in NAc D2-MSNs, like the DRD2 Taq A2 allele, a well-known genetic mechanism protective against SUD normalized nucleus accumbens (NAc) dopamine expression and decreased cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

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