Influence of nicotine form and nicotine flux on puffing behavior and mouth-level exposure to nicotine from electronic nicotine delivery systems.

BACKGROUND: Nicotine form (freebase/protonated) and nicotine flux (rate at which nicotine is emitted) are two factors that can affect the dose of nicotine inhaled by individuals using electronic nicotine delivery systems (ENDS) because they can influence puffing behavior. The nicotine dose for each puff also is directly proportional to nicotine flux (i.e., dose/puff=nicotine flux*puff duration). This study examines the effect of nicotine form and flux on puffing parameters and mouth-level nicotine exposure. METHODS: Thirty-two dual ENDS and combustible cigarette participants completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35µg/sec); a zero-nicotine condition was a negative control. Participants used a Subox Mini C ENDS, powered at 20W, during a 10-puff directed bout (B1) followed by a one-hour ad libitum bout (B2). Puffing parameters and mouth-level nicotine exposure were assessed using the American University of Beirut REALTIME instrument. RESULTS: Relative to protonated nicotine, freebase nicotine was associated with lower total puff duration (puff duration*number of puffs), lower flow rate in B1, lower liquid consumption, and lower mouth-level nicotine exposure. Increasing nicotine flux from 14 to 35µg/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption. Increasing nicotine flux was associated with higher mouth-level nicotine exposure in B1 only. CONCLUSION: ENDS with protonated nicotine may enhance nicotine exposure by promoting longer puffing and thus greater dose delivered. This work highlights the importance of accounting for interactions between nicotine form and flux when considering nicotine regulation for ENDS.

Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials.

INTRODUCTION: Electronic cigarette (EC) use has increased rapidly in the last decade, especially among youth. Regulating nicotine delivery from ECs could help curb youth uptake and leverage EC use in harm reduction yet is complicated by varying device and liquid variables that affect nicotine delivery. Nicotine flux, the nicotine emission rate, is a parameter that incorporates these variables and focuses on the performance rather than the design of an EC. Nicotine flux therefore could be a powerful regulatory tool if it is shown empirically to predict nicotine delivery and subjective effects related to dependence. METHODS AND ANALYSIS: This project consists of two complementary clinical trials. In Trial I, we will examine the relationship between nicotine flux and the rate and dose of nicotine delivery from ECs, hence, impacting abuse liability. It will also examine the extent to which this relationship is mediated by nicotine form (i.e., freebase versus protonated). At Yale School of Medicine (YSM), study participants will puff EC devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. In Trial II, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut (AUB), participants will use EC devices with varying nicotine fluxes and forms, while dependency measures, such as the urge to use ECs, nicotine craving, and withdrawal symptoms, will be assessed. We will also monitor puffing intensity and real-time exposure to toxicants. ETHICS AND DISSEMINATION: The protocol of Trial I and Trial II was approved by YSM and AUB IRBs, respectively. We will disseminate study results through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT05706701 for Trial I and NCT05430334 for Trial II.

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1.

Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by the loss of specific neurons responsible for producing peptide neurotransmitters (orexins/hypocretins), resulting in a sleep-wake cycle disorder. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. To date, no cure has been established for this life-threatening condition. Misdiagnosis of NT1 is also quite common, although it is not exceedingly rare. Therefore, successfully identifying candidate serum biomarkers for NT1 would be a head start for accurate diagnosis and development of therapeutics for this disorder. This study aims to identify such potential serum biomarkers. A depletion protocol was employed for 27 human serum samples (16 NT1 and 11 healthy controls), followed by applying LC-MS/MS bottom-up proteomics analysis, then LC-PRM-MS for validation. The comparison of the proteome profiles of the low-abundant proteins in the samples was then investigated based on age, sex, sample groups, and the presence of the Human Leukocyte Antigen (HLA) DQB1*0602 allele. The results were tracked to gene expression studies as well as system biology to identify key proteins and understand their relationship in the pathogenesis of NT1. Our results revealed 36 proteins significantly and differentially expressed. Among the impaired pathways and bioprocesses, the complement activation pathway is impaired by six of the differentially expressed proteins (DEPs). They are coded by the genes C2, CFB, C5, C1R, C1S, and MASP1, while 11 DEPs are involved in Acute Phase Response Signaling (APRS), which are coded by the genes FN1, AMBP, APOH, CFB, CP, ITIH2, C5, C2, F2, C1, and ITIH4. The combined AUCs of the downregulated and upregulated DEPs are 0.95 and 0.76, respectively. Overall, this study reveals potential serum-protein biomarkers of NT1 and explains the possible correlation between the biomarkers and pathophysiological effects, as well as important biochemical pathways involved in NT1.

Varenicline Treatment for Waterpipe Smoking Cessation.

BACKGROUND: Waterpipe smoking is increasing worldwide with no proven interventions for cessation. We compared abstinence rates with 12-week varenicline therapy versus placebo among habitual waterpipe smokers willing to quit. METHODS: This double-blind placebo-controlled single-center trial, randomized waterpipe smokers from Lebanon who did not smoke other tobacco products to receive varenicline or placebo for 12 weeks. All participants also received three structured 30-minute individual behavioral intervention sessions. The primary outcome was repeated point prevalence abstinence assessed by self-report and verified by exhaled carbon monoxide three times during 12 weeks and analyzed with the intention to treat. End of treatment urine cotinine, weight, blood pressure, anxiety, depression, withdrawal, and adverse symptoms were also assessed. RESULTS: In total, 152 waterpipe smokers (mean age 38 years [SD = 13], 39% females) willing to quit, who smoked waterpipe exclusively (average 2.3 per day [SD = 1.6] for 16.8 years [SD = 10.8]) were randomized. Seventy-nine participants (52%) with any missing abstinence assessment were considered to have relapsed. Repeat point prevalence abstinence rate was numerically higher among the varenicline group compared to placebo, but the difference did not reach statistical significance when assessed by self-report (16.9 vs. 13.6%, respectively, p = .6) and when further verified by exhaled carbon monoxide (14.1% vs. 9.9%, respectively, p = .4). Abstinence rates were similar in both groups when further verified by urine cotinine at end of treatment. No serious adverse events were reported, adverse symptoms and other outcomes were similar in the varenicline and placebo arms. CONCLUSIONS: Varenicline for 12 weeks was not more effective than placebo to achieve abstinence among daily waterpipe smokers. IMPLICATIONS: Varenicline in combination with a behavioral intervention did not significantly enhance the quit rate among exclusive waterpipe smokers compared to behavioral intervention plus placebo. We experienced difficulty enrolling exclusive waterpipe smokers willing to quit and observed high dropout rates among participants demonstrating the difficulties of waterpipe smoking cessation.

Assessing cognitive behavioral therapy for insomnia in individuals with cannabis use disorder utilizing actigraphy and serum biomarkers: A pilot study.

OBJECTIVE/BACKGROUND: This pilot study aims to assess the effect of Cognitive Behavioral Therapy for insomnia (CBTi) in individuals with cannabis use disorder and insomnia. It also aims to investigate the effect of CBTi on levels of serum inflammatory markers in relation to insomnia symptoms. METHODS/PATIENTS: Individuals with cannabis use disorder and insomnia symptoms were recruited over 18 months. Data collected included demographics, self-reported sleep parameters, and cannabis use. Blood samples were drawn to measure IL-2, IL-6, CRP, and cortisol. Participants completed the Insomnia Severity Index questionnaire (ISI) and the Patient Health Questionnaire-4 (PHQ-4), and they were provided with an actigraphy (wrist) device for 1 week before CBTi and a subsequent week after completing the 4 CBTi sessions. RESULTS: Nineteen participants were enrolled in the study. The mean ISI score decreased from moderately severe insomnia at baseline to no clinically significant insomnia after CBTi with a sustained decrease at 3- and 6-months follow-up. Actigraphy showed a significant decrease in sleep onset latency (SOL) after CBTi. Three months after CBTi, 80% of participants reported a decrease in their cannabis use. There was also a significant and sustained decrease in mean PHQ-4 scores after CBTi. Although only trending towards significance, the levels of three out of four biomarkers (IL-2, IL-6, CRP) were decreased 6 months after CBTi. CONCLUSIONS: CBTi is effective as a short- and long-term treatment of insomnia and comorbid anxiety/depression in individuals who regularly use cannabis. A potential added benefit is a reduction in cannabis consumption and inflammatory serum biomarkers.

Is there a therapeutic potential in combining bupropion and naltrexone in schizophrenia?

INTRODUCTION: A sustained-release tablet composed of a combination of the dopamine and norepinephrine reuptake inhibitor bupropion (BUP) and the µ-opioid receptor antagonist naltrexone (NAT) is marketed under the brand name Contrave by Orexigen Therapeutics for appetite control. Minimal literature is available regarding the use of combination bupropion and naltrexone (BUPNAT) in individuals with schizophrenia. AREAS COVERED: In this review, we propose a theoretical model where BUPNAT may have a therapeutic effect in the treatment of schizophrenia. We explore the pathways targeted by the constituent drugs BUP and NAT and summarize the literature on their efficacy and possible adverse effects. We then look at the potential use of BUPNAT in schizophrenia. EXPERT OPINION: Research has hinted that BUP's dopaminergic properties affect the same striatal pathways involved in schizophrenia. NAT, via opioid receptor antagonism, indirectly increases striatal dopamine release by disinhibiting nicotinic acetylcholine receptors. As such, we hypothesize that BUPNAT can have a therapeutic effect in schizophrenia, particularly on negative symptoms. We also suggest that it may ameliorate comorbidities frequently seen in this group of patients, including obesity, smoking, and substance use. Further research and clinical data are needed to elucidate the potential clinical benefits of BUPNAT in the treatment of schizophrenia.

Prevention Strategies of Alcohol and Substance Use Disorders in Older Adults.

Older adults are increasingly engaging in unhealthy substance use. Owing to aging and comorbid medical conditions, older adults are at increased risk of adverse effects from alcohol, tobacco, and illicit drug use. Preventative measures, regular screening, and appropriate intervention can protect older adults from the negative outcomes of substance use and potentially improve their quality of life. This article reviews the latest trends of substance use in older adults, impact on health, and the best practice approaches for the clinical assessment of substance use disorders in this age group.

National trauma and substance use disorders: A slippery slope in Lebanon.

Lebanon, a small middle-income nation in western Asia, has been crippled by decades of political turmoil and armed conflict. A "quadruple crisis" hit the country over the past years, starting with the protracted humanitarian Syrian refugee crisis, followed by a severe socioeconomic collapse, the global COVID-19 pandemic, and lastly the Beirut port catastrophic blast. With the exposure to repetitive traumatic events and associated organic brain injury, the Lebanese population has become at a higher risk of addiction, among other psychiatric comorbidities. With the scarce statistics about the topic and limited addiction services in the country, collaborative local efforts and international help are urgently needed to fight the upcoming substance use epidemic. Raising awareness, providing adequate training, and securing resources for the management of both addiction and trauma are of utmost importance.

Primary Care Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Lebanon: A National Cross-sectional Study.

INTRODUCTION: Substance use among adolescents is on the rise globally. Adolescents rarely seek help for problematic substance use and healthcare professionals can easily fail to identify adolescents with risky substance use. There is therefore a significant global need for substance use screening by healthcare professionals followed by appropriate intervention. Screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based practice that enables clinicians to determine adolescents' risk for substance use and intervene accordingly. However, little effort has been placed on empowering primary care clinicians to use it in Lebanon. We explored the attitudes, perceptions, and practices of primary care nurses and physicians regarding adolescent SBIRT use. METHODS: The study used a cross-sectional multisite survey design targeting urban and rural areas in Lebanon. A national sample of 140 physicians and nurses was recruited using random sampling stratified by governorate. Participants completed mailed or online surveys addressing their practices, attitudes, role perceptions, and self-efficacy regarding SBIRT use. RESULTS: This study revealed that 57.8% of healthcare professionals were not familiar with the SBIRT model and that 76.2% did not practice SBIRT in their setting. The majority addressed the problem of substance use through educating and counseling adolescents about the dangers of substance use (84.2%) and encouraged them to stop (82%) but only 2% reported using standardized instruments for substance use screening. Most participants (88.1%) reported their willingness to use SBIRT in their clinical practice and 92.4% expressed an interest in receiving SBIRT training. Overall, the results showed positive attitudes (M = 4.38, SD = 0.89) and role responsibility (M = 4.47, SD = 1.62) toward addressing substance use in adolescents, in addition to a high level of perceived self-efficacy in addressing substance use (M = 4.04, SD = 0.92). Our results showed minimal differences between nurses' and physicians' perceptions and self-efficacy regarding SBIRT use. CONCLUSIONS: Our study confirms the lack of a standardized approach toward adolescent substance use screening and intervention by primary healthcare providers in Lebanon but revealed the readiness and willingness to receive training and proper support to adopt an evidence-based approach such as SBIRT.

Factors Associated with Mental Health Outcomes: Results from a Tertiary Referral Hospital in Lebanon during the COVID-19 Pandemic.

Coronavirus Disease (COVID-19) has caused global mental health impacts, and healthcare workers (HCWs) face an increased risk of exposure to the disease when compared to the general population. This study aimed to assess factors associated with mental health among Lebanese HCWs six months after the start of the COVID-19 pandemic. A cross-sectional study was conducted among HCWs at a tertiary hospital, in Lebanon between June and July 2020. The survey included data on demographics, exposure to COVID-19, preparedness to COVID-19 outbreak, risk perceptions of COVID-19, and mental health dimensions. Chi-squared and Fisher's exact tests were used to understand the association among these variables. One hundred and ninety-three of 1,600 Lebanese HCWs participated. More than 80% reported high preparedness levels towards the COVID-19 outbreak, 69% believed that their job was putting them at risk, and 70% altruistically accepted these risks. Anxiety and depression symptomatology were present in 24% and 23% of HCWs; who were more likely to feel more stress at work (83% vs 60%; p = 0.004; 82% vs 61%; p = 0.01, respectively), feel afraid of falling ill (72% vs 55%; p = 0.03; 77% vs 54%; p = 0.01, respectively), fear death (21% vs 7%; p = 0.01; 25% vs 6%; p ≤ 0.001, respectively), and believed that people avoided their families (39% vs 21%; p = 0.01; 35% vs 65%; p = 0.02, respectively). HCWs who reported signs of depression were less likely to altruistically accept the risks of caring for COVID-19 patients, compared to those who did not (57% vs 74%; p = 0.03). This study aimed to detect factors associated with mental health among Lebanese HCWs during the COVID-19 pandemic. Findings suggested that altruistic acceptance of COVID-19 risks is higher among HCWs with positive exposure history to COVID-19 and those with less depressive symptomatology.

Comparative effects of psychotropic medications on sleep architecture: a retrospective review of diagnostic polysomnography sleep parameters.

OBJECTIVE: To study the effects of different psychotropic drugs on sleep architecture and sleep-related disorders. MATERIAL AND METHODS: In this retrospective review of 405 consecutive de-identified diagnostic polysomnograms performed at a sleep laboratory from 2007 until 2011, we grouped 347 polysomnograms into five categories: controls, antidepressants (AD), antidepressants + anticonvulsants (ADAC), antidepressants + antipsychotics (ADAP), antidepressants + anticonvulsants + antipsychotics (ADACP). We conducted pairwise comparisons for demographic characteristics, medical history, specific psychotropic medication uses and sleep architecture variables, and adjusted for multiple testing. We used logistic regression to determine the odds ratio of having elevated apnea-hypopnea index (AHI) and periodic limb movement index (PLMI) within each group as compared to controls. RESULTS: Compared to controls, all groups had a significantly higher prevalence of benzodiazepines and trazodone use. AD and ADACP had significantly longer REM latency and lower REM percentage of total sleep time compared to controls. ADAP had a significantly lower AHI compared to controls, but that association was lost in the regression model. AD was associated with a higher PLMI compared to controls. CONCLUSION: Psychotropic polypharmacy does not seem to be associated with significantly deleterious effects on sleep architecture. Adjunct anticonvulsants or antipsychotics to antidepressants may protect against periodic limb movement disorder.

Prevalence of Eating Disorders Among Medical Students in a Lebanese Medical School: A Cross-Sectional Study.

BACKGROUND: Eating disorders are among the most severe psychiatric disorders. Medical students are subjected to high levels of stress and have a high risk of developing burnout and mental health problems, including eating disorders. Due to societal stigma and lack of awareness, it is plausible that disordered eating behaviors among students may go unrecognized and under-reported. The current study aimed to evaluate the prevalence and possible factors associated with eating disorders among medical students at the American University of Beirut in Lebanon (AUB). METHODS: This cross-sectional descriptive study was conducted in 2017 at AUB. Electronic anonymous surveys were sent to all 412 medical students, with a mean age of 23, enrolled in our four-year medical school. In addition to demographic data, students were asked to complete two validated questionnaires, the SCOFF and EAT-26, to assess eating disorders risk. RESULTS: Total responses were 156, out of which 124 completed the whole survey. A total of 131 participants completed the Eat-26 questionnaire and 124 participants completed the SCOFF questionnaire. Out of those, 17% on EAT-26 and 19% on SCOFF were found to be at high risk of developing eating disorders. CONCLUSION: There seems to be a high level of underrecognized and under-treated disordered eating behaviors among female medical students at AUB. Raising awareness among medical students is important, as well as developing better prevention and treatment strategies.

Traumatic brain injury and methamphetamine: A double-hit neurological insult.

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in the world. TBI causes permanent physical, cognitive, social, and functional impairments. Substance use and intoxication are established risk factors for TBI. Data are emerging that also suggest that brain injury might be a risk factor for substance use. Methamphetamine (METH), a highly addictive psychostimulant, has not been thoroughly investigated in the context of TBI exposure. The interplay between the two has been of interest as their pathophysiology intertwines on many levels. However, the knowledge concerning the association between TBI-METH and the impact of chronic METH use on short and long-term TBI outcomes is equivocal at best. In this review of the literature, we postulate that, when combined, these two conditions synergize to result in more significant neuronal damage. As such, chronic exposure to METH before brain trauma may accentuate the pathophysiological signs of injury, worsening TBI outcomes. Similarly, individuals with a history of TBI would be more vulnerable to METH misuse and harmful effects. We, therefore, review the most recent preclinical and clinical data tackling the significant overlap in the pathophysiology of TBI and METH at three levels: the structural level, the biochemical level, and the cellular level. We also highlight some controversial results of studies investigating the outcomes of the interaction between TBI and METH.

Interleukin-2 and the Septohippocampal System: An Update on Intrinsic Actions and Autoimmune Processes Relevant to Neuropsychiatric Disorders.

Recent research suggests that lymphocytes can secrete classic neuropeptides, whereas peripheral immunization may signal hypothalamic neuronal cells. These results have led to more analysis of the function of cytokines as modulators of the peripheral and central nervous systems. In the past, the role of brain cytokines was thought to be a mere redundancy of their activity within the peripheral immune system. Nevertheless, it is currently appreciated that central nervous system (CNS) cytokines have selective effects on neuronal cells. Furthermore, recent research has revealed the involvement of various cytokines in the pathophysiologic processes of neurologic and neuropsychiatric diseases. Yet, despite a plethora of published literature, most of this clinical knowledge remains correlative, and much of the basic research has understandably relied on in vitro experimental designs. However, animal knockout models have provided valuable insight into the complex biology of cytokines, mainly of interleukin-2 (IL-2). Indeed, research has tried to unveil the effects of IL-2 on the septohippocampal system and its associated pathways that regulate learning, memory, and other processes. In this chapter, we provide a comprehensive summary of the studies investigating the role of intrinsic and extrinsic IL-2 in the CNS, particularly at the level of the septohippocampal system. We also discuss the function of other cytokines in this system and propose possible clinical correlates.

Brain Imaging in New Onset Psychiatric Presentations.

We report two cases of patients who presented with psychiatric symptoms and were found to have brain changes on magnetic resonance imaging. In the first case, a 19-year-old man presented with erratic behavior and odd, paranoid ideas. Imaging of the brain revealed a focus of high FLAIR signal involving the left globus pallidus. The second case was a 21-year-old woman who presented with irritability, racing thoughts, and suicidal ideation. Brain imaging revealed nodules of heterotopic grey matter in the right inferior frontal white matter and foci of subcortical heterotopia with thickening of the adjacent cortex. Both patients received psychotropic medications and showed improvement of their symptoms. Integrating neuroimaging in the evaluation of new onset or atypical psychiatric presentations might be of value in specific cases. It is important to develop clear guidelines for the use of imaging modalities in clinical psychiatric practice.

Sleepless in Beirut: Sleep Difficulties in an Urban Environment With Chronic Psychosocial Stress.

STUDY OBJECTIVES: The prevalence of sleep disorders in the Lebanese population is unknown. We assessed the prevalence of insomnia and sleep apnea risk and examined their relationship with sociodemographic, lifestyle, and health characteristics in a sample from Greater Beirut. METHODS: This cross-sectional pilot survey included 501 adults from the community (age 45.2 ± 15.2 years, 64% females). Insomnia symptoms, insomnia disorder, and sleep apnea risk were assessed using the Sleep Heart Health Study and Berlin Questionnaire. Characteristics were compared between individuals with and without insomnia symptoms, insomnia disorder, and sleep apnea. Correlates were assessed using multivariate regression. RESULTS: A total of 44.5% of participants reported insomnia symptoms > 15 nights/mo and 34.5% reported insomnia. Predictors of insomnia symptoms and disorder included female sex (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.01-2.27 and OR 1.76, 95% CI 1.13-2.75, respectively), education level below high school (OR 1.96, 95% CI 1.31-2.95 and OR 2.40, 95% CI 1.52-3.77, respectively) and medical comorbidities (OR 2.27, 95% CI 1.30-3.95 and OR 3.02, 95% CI 1.3-5.27, respectively). Although 31% of participants were at high risk for sleep apnea, only 5% received the diagnosis from a physician. Increased sleep apnea risk was associated with unemployment (OR 1.96, 95% CI 1.11-3.49), high body mass index (OR 1.17, 95% CI 1.11-1.24), snoring (OR 16.7, 95% CI 9.0-31.0), hypertension (OR 4.33, 95% CI 2.28-8.22), arthritis (OR 2.00, 95% CI 1.01-4.01), and other medical comorbidities (OR 2.65, 95% CI 1.24-5.68). CONCLUSIONS: Insomnia and sleep apnea are highly prevalent and likely underdiagnosed in this cohort from Lebanon and are associated with disadvantaged socioeconomic status and medical comorbidities. This alarming prevalence of sleep difficulties and disorders calls for future research exploring the causes including the potential effect of social, economic, and political instability, mental and psychological stress, local customs, and environmental factors.

LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder.

Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an α-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and underlying mechanisms and represent potentially useful biomarkers for disease-associated molecular changes. To test this hypothesis, we assessed the serum glycome of patients with RBD and compared to that of healthy controls. NanoRPLC-MS was used to generate quantitative N-glycan profiles while high-temperature PGC-LC-MS platform was employed to generate quantitative isomeric N-glycan profiles. By analyzing permethylated glycans derived from human blood sera on C18-LC-MS/MS, we identified 59 N-glycan structures in healthy (control) cohort, 56 N-glycans in RBD cohort. Sixteen N-glycans structures were found to be significantly altered in the RBD cohort (p < 0.05). N-glycans with the composition of HexNAc4 Hex5 Fuc1 , HexNAc5 Hex5 , and HexNAc4 Hex5 Fuc1 NeuAc1 presented the most substantial difference between controls and RBD patients (p < 0.01). HexNAc4 Hex5 Fuc1 NeuAc1 showed a relatively high abundance (3.1 ± 0.7% in the control cohort versus 4 ± 3% in the idiopathic RBD cohort). These N-glycans can be potential diagnostic biomarker candidates and provide a window into underlying neurodegenerative processes in patients with idiopathic RBD. In addition, 7 N-glycan isomers were significantly different between controls and RBD patients (p < 0.05). HexNAc4 Hex5 Fuc1 NeuAc1 (4511-2) and HexNAc4 Hex5 Fuc1 NeuAc2 (4512-2) showed the most substantial difference between the control and idiopathic RBD cohorts (p < 0.001). Levels of both these two isomeric structures were higher in the idiopathic RBD cohort. Further larger studies are required to assess the reproducibility of these findings and to elucidate the role played by the changes in glycan structures in the pathogenetic mechanisms of RBD. This information will be instrumental in developing molecular therapeutic targets to promote neuroprotection and prevention of neurodegeneration.

Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach.

OBJECTIVE: To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes. METHODS: Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography-mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD. RESULTS: We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine ß-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology. CONCLUSIONS: Our results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Characteristics of patients presenting post-suicide attempt to an Academic Medical Center Emergency Department in Lebanon.

BACKGROUND: Emergency Department (ED) visits for suicide attempts have been described worldwide; however, the populations studied were predominantly Western European, North American, or East Asian. This study aims to describe the epidemiology of ED patients presenting post-suicide attempt to an academic medical center in Lebanon and to report on factors that affect ED disposition. METHODS: A retrospective cohort study was conducted between 2009 and 2015. Patients of any age group were included if they had presented to the ED after a suicide attempt. Patients with unintentional self-harm were excluded. Descriptive analysis was performed on the demographics and characteristics of suicide attempts of the study population. A bivariate analysis to compare the two groups (hospitalized or discharged) was conducted using Student's t test and Pearson Chi-square where appropriate. A multivariate analysis was then conducted to determine the predictors of hospital admission. RESULTS: One hundred and eight patients were included in the final analysis. Most patients were females (71.4%) and between 22 and 49 years of age. A considerable number of patients were unemployed (43%), unmarried (61.1%), and living with family (86.9%). Most suicide attempts were performed at home (93.5%) and on a weekday (71.3%). The most common mechanisms of injury were overdose with prescription medications (61.3%), overdose with over-the-counter drugs (27.9%), and self-inflicted lacerations (10.1%). The classes of medication most commonly abused were benzodiazepines (39.3%) followed by acetaminophen (27.3%). A large portion of our patients were admitted (70.3%), with the majority going to the psychiatric ward (71.1%). Of note, a quarter (27.5%) of our patients left the ED against medical advice, with 23.5% of admitted patients leaving the hospital before completion of treatment. The main predictors of admission were found to be overdose on prescription medications OR 9.25 (2.12-40.42 CI95%). CONCLUSIONS: The characteristics of our suicide attempters mirror those of international and regional suicide attempters. Further work is required to quantify the effect of voluntary refusal of hospital treatment, the repercussions of family, and financial barriers to healthcare and suicide as a whole in our society.