Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.

RATIONALE: Nicotine dependence is highly comorbid with opioid use disorders (OUDs). The use of nicotine-containing products increases the propensity to misuse prescription opioids and addressing both nicotine and opioid use simultaneously is more efficacious for treatment of OUDs than treating opioid use alone. OBJECTIVES: Given this extreme comorbidity, further elucidation of the effects of nicotine as a factor in promoting vulnerability to development of OUDs is needed. Here, we sought to further explore the effects of nicotine administration on operant self-administration of remifentanil (RMF), a fast-acting synthetic µ-opioid receptor agonist, using a heterogenous seeking-taking chain schedule of reinforcement in unpunished and punished conditions. METHODS: Male and female rats received nicotine (0.4 mg/kg) or saline prior to operant self-administration sessions. These sessions consisted of pressing a 'seeking' lever to gain access to a 'taking' lever that could be pressed for delivery of 3.2 µg/kg RMF. After acquisition, continued drug seeking/taking was punished through contingent delivery of foot-shock. RESULTS: Nicotine, relative to saline, increased RMF consumption. Furthermore, nicotine treatment resulted in significantly higher seeking responses and cycles completed, and this effect became more pronounced during punished sessions as nicotine-treated rats suppressed RMF seeking significantly less than controls. Nicotine treatment functionally reduced the efficacy of foot-shock punishment as a deterrent of opioid-seeking. CONCLUSIONS: Nicotine administration enhanced both appetitive and consummatory responding for RMF and engendered a punishment-insensitive phenotype for RMF that was less impacted by contingent administration of foot-shock punishment. These findings provide further support for the hypothesis that nicotine augments vulnerability for addiction-like behaviors for opioids.

The use of accelerometers to improve estimation of the thermic effect of food in whole room calorimetry studies.

We tested whether spontaneous physical activity (SPA) from accelerometers could be used in a whole-room calorimeter to estimate thermic effect of food (TEF). Eleven healthy participants (63% female; age: 27 ± 4 years; body mass index: 22.8 ± 2.6 kg/m2) completed two 23-hour visits in randomized order: one 'fed' with meals provided and one 'fasted' with no food. SPA was measured by ActivPAL and Actigraph accelerometers. Measured TEF was calculated as the difference in total daily energy expenditure (TDEE) between fed and fasted visits and compared to three methods of estimating TEF: 1) SPA-adjusted TEF (adjTEF)-difference in TDEE without SPA between visits, 2) Wakeful TEF-difference in energy expenditure obtained from linear regression and basal metabolic rate during waking hours, 3) 24h TEF-increase in TDEE above SPA and sleeping metabolic rate. Measured TEF was 9.4 ± 4.5% of TDEE. adjTEF (difference in estimated versus measured TEF: activPAL: -0.3 ± 3.3%; Actigraph: -1.8 ± 8.0%) and wakeful TEF (activPAL: -0.9 ± 6.1%; Actigraph: -2.8 ± 7.6%) derived from both accelerometers did not differ from measured TEF (all p>0.05). ActivPAL-derived 24h TEF overestimated TEF (6.8 ± 5.4%, p=0.002), while Actigraph-derived 24h TEF was not significantly different (4.3 ± 9.4%, p=0.156). TEF estimations using activPAL tended to show better individual-level agreement (i.e., smaller coefficients of variation). Both accelerometers can be used to estimate TEF in a whole-room calorimeter; wakeful TEF using activPAL is the most viable option given strong group-level accuracy and reasonable individual agreement.

Weight Loss Outcomes in a Veterans Affairs Pharmacotherapy-based Weight Management Clinic.

Context: Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world reports on outcomes when AOMs have been used in veterans is limited. Objective: To analyze weight loss outcomes from a local Veterans Health Administration pharmacotherapy-based weight management clinic (WMC). Methods: This was a retrospective cohort study of veterans enrolled in a local WMC for 15 months from August 2016 through September 2018 and followed through November 2019. Patients were offered 1 of 5 available AOMs based on their comorbidities. Factors associated with weight loss (5% or more weight loss) were assessed. Key results: A total of 159 patients were seen in a WMC, 149 (93.7%) veterans were prescribed an AOM, and 129 returned for follow-up. Overall, 61/129 (47%) patients achieved 5% or greater weight loss and 28/129 (22%) achieved 10% or greater weight loss within 15 months. Clinically significant weight loss (%) over the first 15 months was achieved with phentermine/topiramate ER (-6.3%) and liraglutide (-7.5%), but not with orlistat (-3.9%) and lorcaserin (-3.6%). Comorbid obstructive sleep apnea was negatively associated with achieving ≥5% weight loss. Conclusion: Phentermine/topiramate ER and liraglutide were found to be effective AOMs among veterans. Further work is needed to mitigate barriers to AOM initiation given the continued rise in obesity.

Increased risk of attention-deficit/hyperactivity disorder in adolescents with high salivary levels of copper, manganese, and zinc.

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case-control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08-10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58-45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21-13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08-27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

Background: The median eating duration in the U.S. is 14.75 h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12 weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Methods: Eighty-one adults with overweight or obesity (age 18-50 years, BMI 25-45 kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7 days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Results: Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2 ± 6.9 years, BMI 33.8 ± 5.7 kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p = 0.03). Conclusion: There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12 weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

Plasma NfL as a prognostic biomarker for enriching HD-ISS stage 1 categorisation: a cross-sectional study.

BACKGROUND: The recently proposed Huntington's Disease Integrated Staging System (HD-ISS) categorises individuals with the Huntintin genetic mutation into disease progression cohorts based on quantitative neuroimaging, cognitive, and functional markers for research purposes. Unfortunately, many research studies do not collect quantitative neuroimaging data, and so the authors of the HD-ISS have subsequently provided approximated cohort thresholds based on disease and clinical data alone. However, these are rough proxies that aim to maximise stage separation, and should not be considered as 1:1 substitutes for the HD-ISS. Notably, no wet biomarker met the stringent criteria required to be considered a landmark for HD-ISS categorisation. We have previously shown that levels of plasma neurofilament light (NfL), a neuronal marker associated with axonal injury, are associated with predicted years to clinical motor diagnosis (CMD). Our objective in the current study was to determine whether HD-ISS categorisation, particularly for stages prior to CMD, could be improved with consideration of plasma NfL levels. METHODS: A total of 290 blood samples, and clinical measures, were collected from participants across all HD-ISS stages: n = 50 [Stage 0], n = 64 [Stage 1], n = 63 [Stage 2], n = 63 [Stage 3], as well as 50 healthy controls. Plasma NfL levels were measured using a Meso Scale Discovery assay. FINDINGS: Cohorts differed by age, cognitive function, CAG repeat length, and select UHDRS measures. Plasma NfL levels also differed significantly across cohorts. Approximately 50% of Stage 1 participants had plasma NfL levels indicative of predicted CMD within ten years. INTERPRETATION: Our findings suggest that plasma NfL levels may have use in enriching Stage 1 membership into sub-groups that are less than, and within, predicted 10 years until CMD. FUNDING: This work was supported by the National Institutes of Health (NS111655 to E.A.T.); the UCSD Huntington's Disease Society of America Center of Excellence; and the UCSD Shiley-Marcos Alzheimer's Disease Research Center (NIH-NIA P30 AG062429).

Environmental tobacco smoke exposure is associated with increased levels of metals in children's saliva.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been associated with detectable levels of cotinine (a nicotine metabolite) in children's saliva. However, tobacco smoke also contains toxic and essential trace metals, including chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni) and zinc (Zn). OBJECTIVE: The current study examines whether there is a relationship between ETS exposure, as gauged by salivary cotinine, and salivary levels of these metals in a subset (n = 238) of children from the Family Life Project. METHODS: Using inductively-coupled-plasma optical emission spectrophotometry, we measured levels of metals in saliva from children at ~90 months of age. Salivary cotinine was measured using a commercial immunoassay. RESULTS: We found that Cr, Cu, Mn, and Zn were detected in most samples (85-99%) with lower levels of detection for Pb and Ni (9.3% and 13.9% respectively). There were no significant differences in any of the metal concentrations between males and females, nor were levels associated with body mass index, although significant differences in salivary Cr and Mn by race, state and income-to-needs ratio were observed. Children with cotinine levels >1 ng/ml had higher levels of Zn (b = 0.401, 95% CI: 0.183 to 0.619; p = 0.0003) and Cu (b = 0.655, 95% CI: 0.206 to 1.104; p = 0.004) compared to children with levels <1 ng/ml, after controlling for multiple confounders, including sex, race, BMI and income-to-needs ratio. Further, we show that children whose cotinine levels were >1 µg/L were more likely to have detectable levels of Pb in their saliva (b = 1.40, 95% CI: 0.424 to 2.459; p = 0.006) compared to children with cotinine levels <1 ng/ml, also considering confounders. IMPACT STATEMENT: This is the first study to demonstrate significant associations between salivary cotinine and salivary levels of Cu, Zn and Pb, suggesting that environmental tobacco smoke exposure my be one source of increased children's exposure to heavy metals. This study also demonstrates that saliva samples can be used to measure heavy metal exposure, and thus serve as a non-invasive tool for assessing a broader range of risk indicators.

Rapid Detection of Lithium Concentrations in Oral Fluid.

BACKGROUND: Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels. The aim of this study was to evaluate the analytical performance of rapid assays for lithium measurements in oral fluid. METHODS: Levels of lithium in oral fluid from psychiatric patients (n = 108 in total) taking lithium medications were quantified using 2 rapid techniques: an automated clinical chemistry analyzer and a novel, commercially available colorimetric lithium assay. These results were compared with those obtained using inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: The mean and median oral fluid lithium levels in this cohort were 1.43-1.61 mM and 1.32-1.52 mM, respectively, depending on the method, with the overall range, across all methods, being 0.213-4.42 mM. Linear regression analysis showed excellent agreement between the oral fluid values measured using ICP-OES and the colorimetric method (r 2 value = 0.926; P < 0.0001; slope = 1.084 ± 0.038). Similarly, excellent agreement was observed between ICP-OES and the automated method (r 2 = 0.872; P < 0.0001; slope = 1.019 ± 0.057). CONCLUSIONS: These results demonstrate that lithium levels in oral fluid can be rapidly and reliably quantified using colorimetric approaches. These findings may facilitate the development of point-of-care lithium monitoring systems for use in oral fluid.

Escalation of alcohol intake is associated with regionally decreased insular cortex activity but not changes in taste quality.

BACKGROUND: Intermittent access to ethanol drives persistent escalation of intake and rapid transition from moderate to compulsive-like drinking. Intermittent ethanol drinking may facilitate escalation of intake in part by altering aversion-sensitive neural substrates, such as the insular cortex (IC), thus driving greater approach toward stimuli previously treated as aversive. METHODS: We conducted a series of experiments in rats to examine behavioral and neural responses associated with escalation of ethanol intake. First, taste reactivity analyses quantified the degree to which intermittent brief-access ethanol exposure (BAEE) alters sensitivity to the aversive properties of ethanol. Next, we determined whether pharmacological IC inhibition facilitated ethanol escalation. Finally, given that the IC is primary gustatory cortex, we employed psychophysical paradigms to assess whether escalation of ethanol intake induced changes in ethanol taste. These paradigms measured changes in sensitivity to the intensity of ethanol taste and whether escalation in intake shifts the salient taste quality of ethanol by measuring the degree to which the taste of ethanol generalized to a sucrose-like ("sweet") or quinine-like ("bitter") percept. RESULTS: We found a near-complete loss of aversive oromotor responses in ethanol-exposed relative to ethanol-naïve rats. Additionally, we observed significantly lower expression of ethanol-induced c-Fos expression in the posterior IC in exposed rats relative to naïve rats. Inhibition of the IC resulted in a modest, but statistically reliable increase in the acceptance of higher ethanol concentrations in naïve rats. Finally, we found no evidence of changes in the psychophysical assessment of the taste of ethanol in exposed, relative to naïve, rats. CONCLUSIONS: Our results demonstrate that neural activity within the IC adapts following repeated presentations of ethanol in a manner that correlates with reduced sensitivity to the aversive hedonic properties of ethanol. These data help to establish that alterations in IC activity may be driving exposure-induced escalations in ethanol intake.

Salivary Huntingtin protein is uniquely associated with clinical features of Huntington's disease.

Measuring Huntingtin (HTT) protein in peripheral cells represents an essential step in biomarker discovery for Huntington's Disease (HD), however to date, investigations into the salivary expression of HTT has been lacking. In the current study, we quantified total HTT (tHTT) and mutant HTT (mHTT) protein in matched blood and saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 (tHTT) and 2B7-MW1 (mHTT). Matched samples, and clinical data, were collected from 95 subjects: n = 19 manifest HD, n = 34 premanifest HD (PM), and n = 42 normal controls (NC). Total HTT and mHTT levels were not correlated in blood and saliva. Plasma tHTT was significantly associated with age, and participant sex; whereas salivary mHTT was significantly correlated with age, CAG repeat length and CAP score. Plasma and salivary tHTT did not differ across cohorts. Salivary and plasma mHTT were significantly increased in PM compared to NC; salivary mHTT was also significantly increased in HD compared to NC. Only salivary tHTT and mHTT were significantly correlated with clinical measures. Salivary HTT is uniquely associated with clinical measures of HD and offers significant promise as a relevant, non-invasive HD biomarker. Its use could be immediately implemented into both translational and clinical research applications.

Associations between saliva and plasma cytokines in cognitively normal, older adults.

BACKGROUND: Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, especially in elderly populations. METHODS: In this study, we measured levels of 10 cytokines, and the pro-inflammatory factor, YKL-40, in plasma and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; 70.3 ± 6.4 years) using sensitive electrochemiluminescence-based immunoassays. RESULTS: We found that the mean levels of all cytokines were higher in saliva compared to plasma and that strong sex differences were observed for both saliva and plasma cytokines in this population. Comparing each cytokine between the two biofluids, we found that levels of interferon-gamma (IFNγ), interleukin (IL)-6 and tumor necrosis factor-alpha (TNFα) in blood were significantly correlated with their respective levels in saliva. We further observed that levels of these cytokines in blood were significantly correlated with additional cytokines in saliva, including IL-1ß, IL-10, IL-8, IL12p70 and IL-13. CONCLUSIONS: These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting shared inflammatory mechanisms between these two fluids. The higher levels of cytokines measured in saliva suggest that it might represent a better peripheral fluid to gauge inflammatory processes. Finally, our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as disease biomarkers in the elderly and might be related to sex differences in the prevalence of age-related conditions.

Provider Perspectives on the Current Use of Lithium Medications and Lithium Monitoring Practices for Psychiatric Conditions.

Purpose: Despite lithium being a gold standard treatment for bipolar disorder, the percentage of patients with bipolar disorder who are prescribed lithium medication has declined in many parts of the world over the past two decades. The use of lithium is limited by its narrow therapeutic window and adverse side effects, which necessitates frequent serum lithium monitoring; hence, there is a critical need for improved ways to monitor lithium levels in psychiatric patients. We have recently shown that saliva lithium levels are highly correlated with those in blood, thereby presenting an alternative to venipuncture. Saliva sampling could open the door for at-home collections - potential that has been exemplified throughout the COVID-19 pandemic - thereby allowing samples to be collected remotely and delivered to a specific site for testing. In addition, prototype point-of-care devices have been developed by others for serum lithium monitoring, suggesting potential for a saliva lithium monitoring device. Our objective was to query the perspectives of American psychiatrists on lithium treatment practices and obstacles, the potential for at-home saliva collection and point-of-care devices, for lithium monitoring, as an alternative to pathology-based blood testing. Methods: Data was collected through an online, anonymous survey, distributed to American psychiatric societies. Results: Sixty-five respondents from 21 American states completed the survey. The majority of respondents were female, over 65 years of age, and/or had practiced for 30 years or more. The most frequent obstacles encountered with regard to lithium monitoring were adverse drug effects, and the need for monitoring. Overall, respondents believed saliva lithium monitoring and point-of-care devices would be useful, however raised concerns regarding validity and time-delay. Conclusion: Point-of-care devices and saliva lithium monitoring are promising alternatives to blood testing that would be welcomed by psychiatric societies, however, require extensive development and validation before implementation into a clinical setting.

Predictors of posttraumatic stress symptom severity and meaning made in treatment-seeking veterans.

OBJECTIVE: Combat-exposed veterans risk encountering events that disrupt beliefs. To facilitate reduced discrepancy between prior beliefs and current trauma appraisals, veterans may engage in a process of meaning-making. Meaning-making can lead to positive outcomes, such as integrating the traumatic event into one's life narrative or adapting global meaning (meaning made) or elicit distress. Given these potentially different outcomes, this study examined potential correlates of posttraumatic stress symptom (PTSS) severity and meaning made, including relationship attachment dimensions of anxiety and avoidance, and difficulties with emotion regulation, while controlling for combat exposure. METHOD: Veterans receiving mental health services at a Veterans Affairs (VA) Medical Center and a VA community-based outpatient clinic (N = 130) completed measures through a paper-and-pencil survey. Almost all participants (92%) were male, with a mean age of 55.92 years. RESULTS: In terms of meaning made, lower levels of attachment anxiety and emotional clarity (an aspect of emotion regulation) predicted higher meaning made. In terms of PTSS severity, higher attachment avoidance, attachment anxiety, and difficulties engaging in goal-directed behavior (an aspect of emotion regulation) significantly predicted higher PTSS severity. CONCLUSION: Aspects of both attachment style and emotion regulation difficulties affect meaning made and PTSS severity. These constructs may be especially relevant for clinicians working with veterans to help PTSS and support meaning made postcombat.

Early time-restricted eating compared with daily caloric restriction: A randomized trial in adults with obesity.

OBJECTIVE: This trial aimed to evaluate the acceptability and efficacy of early time-restricted eating plus daily caloric restriction (E-TRE+DCR) compared with DCR alone within a behavioral weight-loss intervention. METHODS: Participants (n = 81, 69 women, mean [SD] age: 38.0 [7.8] years, BMI: 34.1 [5.7] kg/m2 ) were randomized to E-TRE (10-hour eating window starting within 3 hours of waking) plus DCR or DCR alone (~35% DCR) for 39 weeks. The primary outcome was body weight (measured with digital scale) at week 12. Secondary outcomes measured at week 12 included hemoglobin A1c, lipids, energy intake (photographic food records), physical activity (accelerometry), dietary adherence (questionnaires), and body composition (dual-energy x-ray absorptiometry). Weight and body composition were also assessed at week 39. RESULTS: Mean [SD] weight loss was not different between groups at week 12 (E-TRE+DCR: -6.2 [4.1] kg vs. DCR: -5.1 [3.2] kg) or at week 39 (E-TRE: -4.9 [5.3] kg vs. DCR: -4.3 [5.3] kg). There were no between-group differences in changes in body composition, dietary adherence, energy intake, physical activity, hemoglobin A1c, or lipids at week 12. CONCLUSIONS: E-TRE+DCR was found to be an acceptable dietary strategy, resulting in similar levels of adherence and weight loss compared with DCR alone.

Associations between prognostic index scores and plasma neurofilament light in Huntington's disease.

INTRODUCTION: The inclusion of premanifest Huntington's Disease (Pre-HD) subjects in clinical trials necessitates selecting those who are near transition to manifest Huntington's disease (Man-HD). We previously determined that plasma neurofilament light (NfL) levels are significantly correlated with predicted years to Man-HD onset, using established formulae. Recently, a new normalized prognostic index (PIN) score for predicting Pre-HD disease progression has been validated. Our objective was to determine whether plasma NfL levels are similarly associated with PIN score and PIN score-derived years to Man-HD onset (PIN-YTO). METHOD: 112 individuals (46 Pre-HD, 66 Man-HD) underwent blood sample collection and clinical assessment, inclusive of the Symbol Digit Modalities Test and Unified Huntington's Disease Rating Scale Total Motor Score. Plasma NfL levels were measured using a Meso Scale Discovery assay. RESULTS: Pre-HD and Man-HD cohorts differed by age (p < .0001), and CAG repeat number (p = .004), but not education level or gender. Plasma NfL levels were significantly correlated with PIN scores (r = 0.69, p < .0001) and PIN-YTO (r = -0.69, p < .0001). Plasma NfL levels were similarly correlated with predicted years to onset scores determined using Langbehn and colleague's formula (r = -0.68, p < .0001). All significant correlations endured corrections for age and CAG repeat number. A plasma NfL cut-point of <45.0 pg/ml distinguished Pre-HD participants >10 predicted years from Man-HD onset, compared to those ≤10 predicted years. CONCLUSIONS: We have extensively shown that plasma NfL levels are associated with predicted years to manifest HD onset in Pre-HD participants, and present a plasma NfL cut-point that may help exclude far-from-onset Pre-HD patients from clinical trials.

Salivary S100 calcium-binding protein beta (S100B) and neurofilament light (NfL) after acute exposure to repeated head impacts in collegiate water polo players.

Blood-based biomarkers of brain injury may be useful for monitoring brain health in athletes at risk for concussions. Two putative biomarkers of sport-related concussion, neurofilament light (NfL), an axonal structural protein, and S100 calcium-binding protein beta (S100B), an astrocyte-derived protein, were measured in saliva, a biofluid which can be sampled in an athletic setting without the risks and burdens associated with blood sampled by venipuncture. Samples were collected from men's and women's collegiate water polo players (n = 65) before and after a competitive tournament. Head impacts were measured using sensors previously evaluated for use in water polo, and video recordings were independently reviewed for the purpose of validating impacts recorded by the sensors. Athletes sustained a total of 107 head impacts, all of which were asymptomatic (i.e., no athlete was diagnosed with a concussion or more serious). Post-tournament salivary NfL was directly associated with head impact frequency (RR = 1.151, p = 0.025) and cumulative head impact magnitude (RR = 1.008, p = 0.014), while controlling for baseline salivary NfL. Change in S100B was not associated with head impact exposure (RR < 1.001, p > 0.483). These patterns suggest that repeated head impacts may cause axonal injury, even in asymptomatic athletes.

The effects of the COVID-19 pandemic on weight loss in participants in a behavioral weight-loss intervention.

OBJECTIVE: This study aimed to assess the effects of the COVID-19 pandemic on weight loss, physical activity, and sleep in adults with overweight or obesity participating in a 39-week weight-loss intervention. METHODS: Participants (n = 81, 85% female, mean [SD] age 38.0 [7.8] years, BMI 34.1 [5.7] kg/m2 ) were enrolled in 3 separate cohorts. Cohorts 1 and 2 were studied prior to the pandemic (pre-COVID cohorts). Cohort 3 (COVID cohort) transitioned to a virtual intervention at week 6, when "stay-at-home" orders were implemented in Colorado. Weight was assessed at baseline, week 12, and week 39 with clinic scales before the pandemic and home scales during the pandemic. Diet was assessed with Likert scales at weeks 4, 8, and 12. Physical activity and sleep were assessed at baseline and week 12 with actigraphy. RESULTS: Participants in the COVID cohort reported greater dietary adherence (p = 0.004) and lost more weight than those in the pre-COVID cohorts at week 12 (-7.7 [3.3] kg vs. -3.7 [3.0] kg, p < 0.001) and week 39 (-8.5 [4.4] kg vs. -2.8 [4.6] kg, p < 0.001). Energy intake did not differ between cohorts (p = 0.51). The COVID cohort increased both sedentary time while awake and time in bed at night. CONCLUSIONS: Although the pandemic caused disruptions for the COVID cohort, participants still achieved weight loss with continued behavioral support.

Improving lifestyle obesity treatment during the COVID-19 pandemic and beyond: New challenges for weight management.

Objective: The COVID-19 pandemic has resulted in significant changes to daily life and many health-related behaviors. The objective of this study was to examine how the stay-at-home/safer-at-home mandates issued in Colorado (March 2020-May 2020) impacted lifestyle behaviors and mental health among individuals with overweight or obesity participating in two separate behavioral weight loss trials (n = 82). Methods: Questionnaires were used to collect qualitative and quantitative data on challenges to weight loss presented by the COVID-19 pandemic, including changes in dietary intake, physical activity, sedentary behavior, and mental health during the stay-at-home/safer-at-home mandates. Results: Using a convergent mixed method approach integrating qualitative and quantitative data, the greatest challenge experienced by participants was increased stress and anxiety, which led to more unhealthy behaviors. The majority perceived it to be harder to adhere to the prescribed diet (81%) and recommended physical activity (68%); however, self-reported exercise on weekdays increased significantly and 92% of participants lost weight or maintained weight within ±1% 5-6 weeks following the stay-at-home mandate. Conclusion: Study results suggest that obesity treatment programs should consider and attempt to address the burden of stress and anxiety stemming from the COVID-19 pandemic and other sources due to the negative effects they can have on weight management and associated behaviors.

Saliva testing as a means to monitor therapeutic lithium levels in patients with psychiatric disorders: Identification of clinical and environmental covariates, and their incorporation into a prediction model.

OBJECTIVE: The narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitudinal salivary lithium level monitoring. METHODS: We measured salivary lithium levels using ICP-OES in n = 169 passive drool samples, collected both as single observations and longitudinally for up to 18 months, from a multi-center cohort of n = 75 patients with bipolar disorder or other psychiatric conditions. RESULTS: Saliva and serum lithium levels were highly correlated. Adjustment for daily lithium dose, diabetes, and smoking improved this relationship (r = 0.77). Using the adjusted intersubject equation and a patient's salivary lithium value, we observed a strong correlation between the predicted vs. observed serum lithium levels (r = 0.70). Most patients had highly stable saliva/serum ratios across multiple visits, with longitudinal variability significantly greater with age. Use of the intrasubject saliva/serum ratio from a single prior observation had similar predictive power to the use of the adjusted intersubject equation. However, the use of the mean intrasubject ratio from three prior observations could robustly predict serum lithium levels (predicted vs. observed r = 0.90). CONCLUSIONS: These findings strongly suggest that saliva could be used for lithium monitoring, and open the door for the development and implementation of a point-of-care salivary lithium device for use at home or the clinic. We propose that the use of saliva will dramatically improve treatment opportunities for patients with mood disorders.

Relationships among non-interpersonal and interpersonal trauma types, posttraumatic stress, and posttraumatic growth.

METHODS: Adults seeking behavioral health or medical treatment (N = 158) were recruited from a community healthcare agency and a residential support program in the southeastern United States. RESULTS: Individuals who reported interpersonal trauma had significantly higher total PTS severity and symptom clusters. No significant difference was found in perceived PTG based on trauma type. No significant curvilinear relationship between PTS and perceived PTG was found. A significant negative linear relationship was observed between PTS and perceived PTG for non-interpersonal trauma, but not interpersonal trauma. CONCLUSION: Trauma type may influence the PTS and perceived PTG relationship and, while associated with PTS, seems less important to reporting of perceived PTG.