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Globally, suicide is a public health concern that claims the lives of many each year. The complex etiology and factors contributing to the risk of suicide make it hard to predict the likelihood of death by suicide. Suicide rates have been increasing over the past 25 years in patients aged 65 years and older, and with the expected increases in the size of the older adult population and the under-detection of suicide risk, these rates may continue to increase. To mitigate and attempt to limit this expected increase, it is important to understand the risk and protective factors of suicide in older adults. This narrative review focuses on individuals above the age of 65 and encompasses relevant peer-reviewed publications from the past 25 years to cover fatal and non-fatal suicidal behaviour. It summarizes several important risk factors for suicide and suicidal behaviors while considering how risk can be detected, assessed, prevented, and mitigated. Screening methods to detect suicide and depression in older adults were examined based on their effectiveness and suitability for use in this population. Lastly, the impacts of the COVID-19 pandemic on suicide rates in older adults were described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sadek, Diaz-Piedra, Saleh and MacDonald.)

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that disrupts brain functioning and is characterized by hyperactivity, impulsivity, and inattention. With varying presentations and complex etiological factors contributing to the development of ADHD, along with its persistence into adulthood, ADHD must be studied. Researchers have taken an interest in the relationship between ADHD and suicide, which is a serious public health concern with increasing prevalence rates in the Americas. The current literature reveals conflicting views on the importance of psychiatric comorbidities in the development of suicidal behaviours in ADHD patients. Therefore, this study aimed to determine whether there were significant differences between adult ADHD patients with suicide risk and adult ADHD patients without suicide risk. This study was a naturalistic retrospective chart review pilot study that used a sample of adults with a confirmed diagnosis of ADHD from January 2023 to August 2023. Using convenience sampling and sets of inclusion and exclusion criteria, patient data were sequentially collected from Med Access electronic medical records. The control and experimental groups each consisted of 50 patients (100) ranging from 19 to 58 years old. Our quantitative data were analyzed using non-parametric statistical tests, including the Chi-Square test and the Mann-Whitney U test. The results showed significant associations between ADHD patients with suicide risk and (1) borderline personality disorder; (2) binge eating disorder; (3) seven specific psychosocial risk factors; and (4) a higher number of antidepressant medication trials. No significant associations were found with other psychiatric disorders; however, there are important sex differences in terms of the risk factors. Our pilot study reveals several significant differences between adult ADHD patients with suicide risk and those without suicide risk. However, given our limited sample size and limitations, we hope our study encourages larger-scale studies to further investigate this relationship to improve its generalizability.

Introduction: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that interferes with multiple aspects of daily functioning and is associated with impairments in several domains. It may affect academic, educational, vocational, social, emotional, interpersonal, and health domains, and worsen risks to health outcomes., Objective: To identify and discuss medical conditions that commonly present with symptoms resembling ADHD., Method: This review is selective and not systematic. It is conducted through a focused literature search through PubMed, Google Scholar, and EMBASE. Search term included "ADHD misdiagnosis", "medical conditions with ADHD like symptoms", "ADHD AND medical problems"., Exclusion: giftedness, high IQ, and any article that does not list medical conditions. The limits applied were the following: the work must have been published in the past 20 years, be on humans, and be in the English language., Results: There are several medical conditions that can be misdiagnosed as ADHD and may show a similar presentation to ADHD, particularly with inattentive symptoms. Examples include, but are not limited to, absence seizure disorder, diabetes, thyroid dysfunction, sleep deprivation, post-concussion states, inflammatory bowel disease, iron deficiency states and anemia, and disordered breathing., Conclusions: Our review suggests that a thorough medical evaluation should be conducted prior to the diagnosis of ADHD. Allied health professionals and psychologists who diagnose ADHD should seek medical clearance from a physician prior to making the ADHD diagnosis in order to reduce misdiagnosis rates and improve patient outcomes. ADHD diagnosis should follow guidelines and be carried out under a systematic standardized approach. A full medical evaluation should be conducted to assess for medical conditions that may look like ADHD or be associated with ADHD.

This narrative review examines two of the common comorbidities of attention-deficit/hyperactivity disorder, bipolar disorder (BD), and borderline personality disorder (BPD), which each share several common features with ADHD that can make assessment and diagnosis challenging. The review highlights some of the key symptomatic differences between adult ADHD and these disorders, allowing for more careful consideration before establishing a formal diagnosis. When the disorders are found to be comorbid, further complications may arise; thus, the review will also help to provide evidence-based treatment recommendations as well as suggestions on how to minimize adverse events. Incorporating evidence from systematic reviews, journal articles, randomized controlled trials, and case reports, this review highlights that the diagnosis of ADHD and some of its common comorbidities is challenging and requires full, in-depth assessment and management. The management strategies of these comorbidities will also be addressed, with emphasis on achieving mood stabilization for BD prior to initiating appropriate ADHD pharmacotherapy. Medications, specifically mood stabilizers, antipsychotics, and antidepressants, are fundamental in treating symptoms seen in BD and some cases of BPD, alongside psychotherapy and lifestyle modifications when appropriate. The review highlights the effectiveness of specific medications, including psychostimulants, atomoxetine, and bupropion, as add-on therapies to mood-stabilizing treatments for addressing ADHD symptoms in patients with these comorbidities. Despite limited research, the review will address various pharmacological and psychotherapeutic approaches for managing comorbid ADHD and BPD, emphasizing the need for further investigations to better understand the unique needs of this patient population.

This study was a retrospective pilot chart review of adult attention deficit hyperactivity disorder (ADHD) patients diagnosed with and without comorbid binge eating disorder (BED) and borderline personality disorder (BPD). ADHD research is critical because of its prevalence and persistence into adulthood. In the literature, ADHD, BED, and BPD are linked to an underlying impulsivity factor. This comparative study examined whether differences existed between patient groups concerning risk factors, comorbid disorders, and continuous performance test (CPT) cognitive scoring. The main goal was to find significant associations suggestive of correlations between specific factors and a principal diagnosis of ADHD with comorbid BED and BPD. Study participants were patients between 18 and 30 diagnosed by a psychiatrist in an outpatient clinic between June 2022 and December 2022. Both the control and comorbidity groups included 50 participants (N = 100). Patients were randomly chosen based on the chronological order of intake visit dates at the clinic and were selected as participants upon meeting the inclusion criteria. Data were collected through the Med Access EMR database, with quantitative data analyzed using SPSS and chi-squared p -value tests. The results showed significant associations between a principal diagnosis of ADHD with comorbid BPD and BED and (1) having four or more overall risk factors; (2) having five specific reported psychosocial risk factors: family issues, bullying, poverty, trouble with the law, and physical abuse; and (3) having on average more risk factors and comorbidities as compared to ADHD patients without comorbid BPD and BED. No association was found between low CPT scores and, thus, differential cognitive functionality between groups. This research will inform future study hypotheses to develop the clinical profile of ADHD patients with comorbid BED and BPD.

mRNA stability is the mechanism by which cells protect transcripts allowing their expression to execute various functions that affect cell metabolism and fate. It is well-established that RNA binding proteins (RBPs) such as HuR use their ability to stabilize mRNA targets to modulate vital processes such as muscle fiber formation (myogenesis). However, the machinery and the mechanisms regulating mRNA stabilization are still elusive. Here, we identified Y-Box binding protein 1 (YB1) as an indispensable HuR binding partner for mRNA stabilization and promotion of myogenesis. Both HuR and YB1 bind to 409 common mRNA targets, 147 of which contain a U-rich consensus motif in their 3' untranslated region (3'UTR) that can also be found in mRNA targets in other cell systems. YB1 and HuR form a heterodimer that associates with the U-rich consensus motif to stabilize key promyogenic mRNAs. The formation of this complex involves a small domain in HuR (227-234) that if mutated prevents HuR from reestablishing myogenesis in siHuR-treated muscle cells. Together our data uncover that YB1 is a key player in HuR-mediated stabilization of pro-myogenic mRNAs and provide the first indication that the mRNA stability mechanism is as complex as other key cellular processes such as mRNA decay and translation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

ScanMedicine is a novel searching system dedicated to providing health care professionals, patients, carers, the public, decision- and policy-makers, and researchers with open access to the development pipeline underpinning health technology innovations. In the first phase of developing ScanMedicine, we have focused on capturing and consolidating clinical trial records hosted on national and international clinical trials registries and medical device approval data from the FDA. ScanMedicine has been developed based on microservice architecture allowing the system to be constantly improved in a flexible and scalable manner. ScanMedicine offers users a convenient and effective single search interface with interactive visualisation features that can provide an overview of the health technology innovation landscape., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Loss of control eating (LOC-E) in youth predicts the later development of full-syndrome binge-eating disorder (BED), and therefore, could be a relevant target for prevention treatments. To develop these treatments, it is important to understand the underlying disease processes and mechanisms. Based on the putative role of neurocognitive impairments in the pathogenesis of LOC-E, treatments that modulate these neurocognitive factors warrant further exploration. For instance, stimulants are an effective treatment for impulsivity in youth with attention deficit/hyperactivity disorder (ADHD) and have been shown to improve symptoms of BED in adults. Notably, stimulants have not been examined as a treatment for LOC-E in youth. To explore this gap, we aim to measure change in LOC-E episodes and secondary outcomes in youth with comorbid ADHD and LOC-E who are being started on stimulants., Methods: We will collect prospective observational data on forty 8-to-13-year-old youth diagnosed with comorbid ADHD and LOC-E who are initiating a stimulant for ADHD. Prior to stimulant initiation, participants will complete baseline measures including LOC-E episode frequency in the last 3 months (primary outcome), and secondary outcomes including disordered eating cognitions, emotions and behaviors, ADHD symptom severity, parental LOC-E, impulsivity and reward sensitivity, and anxiety/mood severity. Outcome measurements will be gathered again at 3-months after initiating the stimulant. Within-patient standardized effect sizes with 95% confidence intervals will be calculated from baseline to 3-month follow-up for all outcomes., Discussion: Many individuals with LOC-E or binge eating do not fully remit over the course of psychotherapy. Whereas psychotherapy may address psychological and sociocultural domains associated with LOC-E, some individuals with neurocognitive impairments (e.g., ADHD) and neurobiological deficits (e.g., low intrasynaptic dopamine or norepinephrine) may benefit from adjunctive treatment that targets those factors. This will be the first study to provide pilot data for future studies that could examine both the effect of stimulants on LOC-E in youth and underlying mechanisms., Trial Registration: Trial registration number: NCT05592119., (© 2022. The Author(s).)

Multiple psychosocial interventions to treat ADHD symptoms have been developed and empirically tested. However, no clear recommendations exist regarding the utilization of these interventions for treating core ADHD symptoms across different populations. The objective of this systematic review and meta-analysis by the CADDRA Guidelines work Group was to generate such recommendations, using recent evidence. Randomized controlled trials (RCT) and meta-analyses (MA) from 2010 to 13 February 2020 were searched in PubMed, PsycINFO, EMBASE, EBM Reviews and CINAHL. Studies of populations with significant levels of comorbidities were excluded. Thirty-one studies were included in the qualitative synthesis (22 RCT, 9 MA) and 24 studies (19 RCT, 5 MA) were included in the quantitative synthesis. Using three-level meta-analyses to pool results of multiple observations from each RCT, as well as four-level meta-analyses to pool results from multiples outcomes and multiple studies of each MA, we generated recommendations using the GRADE approach for: Cognitive Behavioral Therapy; Physical Exercise and Mind-Body intervention; Caregiver intervention; School-based and Executive intervention; and other interventions for core ADHD symptoms across Preschooler, Child, Adolescent and Adult populations. The evidence supports a recommendation for Cognitive Behavioral Therapy for adults and Caregiver intervention for Children, but not for preschoolers. There were not enough data to provide recommendations for the other types of psychosocial interventions. Our results are in line with previous meta-analytic assessments; however, they provide a more in-depth assessment of the effect of psychosocial intervention on core ADHD symptoms., Competing Interests: The authors declare no conflict of interest.

Background: The last decade has shown a remarkable increase in the rates of illicit opioid use in Canada and internationally, which is associated with large increases in opioid related morbidity and mortality. While the differences between methadone and buprenorphine/naloxone in terms of retention have been studied outside Canada, the unique location and design of this study, gives it a specific significance., Objectives: This study aims to describe the relative treatment retention rates for first episode opioid replacement treatment between methadone and buprenorphine/naloxone for patients receiving daily witnessed dispensed medications in Nova Scotia., Methods: A longitudinal retrospective descriptive study analyzing secondary data from the Nova Scotia Prescription Monitoring Program on patients 18 years of age and older who started first episode opioid agonist therapy with methadone or buprenorphine/naloxone for opioid use disorder in Nova Scotia between 2014 and 2018. Treatment episode was defined as date of initial opioid agonist prescription until there is a gap of greater than 6 days without receiving opioid agonist medication at a pharmacy., Results: One thousand eight hundred sixty-seven of whom were analyzed as they had at least 1 day in treatment. There was significant treatment dropout within the first 2 weeks of treatment, which did not show a significant difference between OAT medication (23.4% of buprenorphine/naloxone; 22.2% methadone). Median duration of retention in treatment was 58 days for those treated with buprenorphine/naloxone and 101 days for patients treated with methadone. Multivariate cox proportional hazards model showed that buprenorphine/naloxone use as compared to methadone lead to increased hazard of treatment dropout by 62% (HR = 1.62). Hazard rate of treatment dropout for patients below 25 years of age was calculated. (HR 1.53). Median duration of retention in treatment for this subgroup of patients younger than age 25 was 37.5 days for patients treated with buprenorphine/naloxone and 69 days for patients treated with methadone., Conclusions: Our data suggests that methadone is a numerically superior medication for opioid use disorder when the metric of treatment retention is viewed in isolation, for our population in Nova Scotia. However, the results should be interpreted carefully considering the number of limitations of this study. There are social/accessibility, pharmacologic/safety, and patient preference factors which are also key in decision making when prescribing opioid agonist therapy. These must all be considered when deciding on which medication to initiate for a patient beginning a new treatment episode with OAT for opioid use disorder. This study should stimulate further research into this important area in addiction medicine., (© 2022. The Author(s).)

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that interferes with multiple aspects of daily functioning. Malingering or feigning of symptoms can be a major challenge during ADHD assessment. Stimulant medication abuse, misuse and diversion may constitute another challenge during management. A literature search of the past 15 years on the topic continued to suggest that there are several reasons for malingering and faking ADHD symptoms. Some of the reasons include the intent to obtain prescriptions for stimulant medications for performance enhancement, to gain access to additional school services and accommodations, to use recreationally and to sell as a street drug. In some countries, patients may receive additional tax or student loan benefits. Several researchers suggested that self-report rating measures are easily simulated by patients without ADHD. They concluded that no questionnaire has proved sufficiently robust against false positives. Some clinical factors that may suggest malingering during the ADHD assessment are highlighted and some available tests to detect malingering are discussed.

Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that results from complex interactions of multiple genes and environmental risk and adversity factors. Some researchers have suggested a need for additional research into differing clinical presentations of ADHD for further classification. In this context, this study aimed to investigate whether increases in risk and adversity factors increase the severity of ADHD and the number of comorbid psychiatric disorders. This is a naturalistic retrospective chart review exploratory study in 100 patients 16 years or older who have a confirmed diagnosis of ADHD. The quantitative data were analyzed using SPSS, using the Mann-Whitney test for parametric data and the Chi-square and Kruskal-Wallis p value tests for non-parametric and categorical data. Qualitative data were tabulated and described. The study found that (1) the average number of comorbidities increases with the severity of ADHD, (2) the average number of risk and adversity factors increases with the severity of ADHD, (3) the number of risk and adversity factors were positively associated with the number of comorbidities, and (4) Level of education was negatively associated with the number of risk and adversity factors and the number of comorbidities. The implications of these findings are discussed, and future research in this important area is suggested.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has deeply altered social and working environments among health care workers. These health care workers are therefore at risk of additional psychosocial strain and ensuing metal health symptoms, which indirectly affects patient care. In this study, we aimed to assess the psychosocial and psychopathological impact of COVID-19 among acute care mental health and addictions staff., Methods: This study is a cross-sectional survey and contains a sample size of 60 mental health and addiction acute care workers recruited from within Nova Scotia Health Authority. The survey was constructed using the online survey system, Opinio, and consisted of three sections: demographic variables (gender, age group and profession); the DASS-21 Questionnaire (which provides dimensional measures of stress, anxiety and depression); and the MBI-HSS (MP) Questionnaire (which measures three dimensions of burnout-emotional exhaustion, depersonalization and personal achievement)., Results: The majority of participants had at least one pathologic score on the DASS-21 and MBI-HSS (MP) sections (75.5% and 93.5%, respectively). The median severity on the DASS-21 and MBI-HSS (MP) were both moderate, with the younger age group (20-35 years) having more significant burnout scores (p = 0.0494). Simple logistic regression showed a significant relationship between burnout severity and pathologic distress, and simple linear regression showed significant correlation between DASS-21 and MBI-HSS (MP) scores, with a R2 value of 0.4633., Conclusion: More planning, programs, resources and further research are needed to support wellness and recovery of all health care professionals who work at the mental health and addictions acute care unit.

Introduction: Postpartum hemorrhage that occurs frequently with placenta previa is one of the causes of maternal mortality in 14% in developing countries., Objective: To assess efficacy of cervical inversion as a tamponade in controlling bed of placenta in cases of placenta previa., Patients and Method: A prospective randomized controlled study was conducted among a total of 240 pregnant women with placenta previa (120 subjected to Alalfy modified cervical inversion technique plus hemostatic sutures and 120 was not subjected cervical inversion and only was subjected to hemostatic sutures in Obstetrics and Gynecology Department at Suez Canal University hospital, Helwan University and Algezeerah hospital for a planned cesarean section)., Results: The mean intraoperative blood loss, the intraoperative time, and the postoperative hemoglobin show a statistically significant difference between cases with placenta previa who were exposed to cervical inversion in comparison to cases that had no cervical inversion with a p -value <.001., Conclusion: Modified cervical inversion (Alalfy technique) as a tamponade when added to hemostatic sutures to the placental bed is an easy, rapid, and efficient procedure that can decrease the amount of blood loss, time needed to stop bleeding per bed, total operative time, also it can decrease the need for blood transfusion.

Preoperative optimization has not been explored comprehensively in the surgical literature, as this responsibility has often been divided among surgery, anesthesia and medicine. We developed an evidence-based clinical practice guideline to summarize existing evidence and present diagnostic and treatment algorithms for use by surgeons caring for patients scheduled to undergo major elective surgery. We focus on 3 common comorbid conditions seen across surgical specialties - anemia, hyperglycemia and smoking - as these conditions increase complication rates in patients undergoing major surgery and can be optimized successfully as soon as 6-8 weeks before surgery. With the ability to address these conditions earlier in the patient journey, surgeons can positively affect patient outcomes. The aim of this guideline is to bring optimization in the preoperative period under the existing umbrella of evidence-based surgical care., Competing Interests: Competing interests: Kerri Mullen is a named inventor of the Ottawa Model for Smoking Cessation, an intellectual property of the University of Ottawa Heart Institute. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Cachexia syndrome develops in patients with diseases such as cancer and sepsis and is characterized by progressive muscle wasting. While iNOS is one of the main effectors of cachexia, its mechanism of action and whether it could be targeted for therapy remains unexplored. Here, we show that iNOS knockout mice and mice treated with the clinically tested iNOS inhibitor GW274150 are protected against muscle wasting in models of both septic and cancer cachexia. We demonstrate that iNOS triggers muscle wasting by disrupting mitochondrial content, morphology, and energy production processes such as the TCA cycle and acylcarnitine transport. Notably, iNOS inhibits oxidative phosphorylation through impairment of complexes II and IV of the electron transport chain and reduces ATP production, leading to energetic stress, activation of AMPK, suppression of mTOR, and, ultimately, muscle atrophy. Importantly, all these effects were reversed by GW274150. Therefore, our data establish how iNOS induces muscle wasting under cachectic conditions and provide a proof of principle for the repurposing of iNOS inhibitors, such as GW274150 for the treatment of cachexia., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Although Attention Deficit Hyperactivity Disorder (ADHD) is associated with an increased risk of substance use disorder (SUD), existing literature on how SUD interacts with ADHD outcomes is limited. This study investigates whether SUD among individuals with ADHD is associated with worse ADHD outcomes and prognosis, and the association between overall functioning and SUD. In addition, we seek to understand whether heavy cannabis use is a better predictor of poorer outcomes compared to SUD status alone., Method: We conducted a retrospective analysis on 50 ADHD patient charts, which were allocated based on SUD status. Subgroup analysis was performed on the total sample population, with allocation based on heavy cannabis use. Mann-Whitney and Chi-Square tests were used for both the primary and subgroup analyses., Results: SUD status highly correlated with more ADHD-related cognitive impairments and poorer functional outcomes at the time of diagnosis. ADHD patients with comorbid ADHD-SUD scored significantly lower (p = < 0.0001) on objective cognitive testing (Integrated Auditory and Visual Continuous Performance Test (IVA/CPT)) than ADHD patients without SUD. The correlation with poorer ADHD outcomes was more pronounced when groups were allocated based on heavy cannabis use status; in addition to significantly lower IVA/CPT scores (p = 0.0011), heavy cannabis use was associated with more severe fine motor hyperactivity and self-reported hyperactivity/impulsivity scores (p = 0.0088 and 0.0172, respectively)., Conclusion: Future research is needed to determine how substance abuse can be a barrier to improved ADHD outcomes, and the effect cannabis and other substances have on cognitive function and pharmacotherapy of ADHD.

Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN)., Method: An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined., Results: Eighteen of 23 participants completed the study per protocol. There was no participant-initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent-to-treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End-of-Treatment (mean difference = -29.83, 95% confidence interval: -43.38 to -16.27; and mean difference = -33.78, 95% confidence interval: -48.74 to -18.82, respectively)., Discussion: Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long-term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested., Trial Registration Number: NCT03397446., (© 2021 Wiley Periodicals LLC.)

Background: Smoking cessation programs started as late as 4 weeks before surgery reduce perioperative morbidity and death, yet outpatient clinic interventions are rarely provided. Our aim was to evaluate the feasibility of implementing a tobacco treatment protocol designed for an outpatient surgical setting., Methods: We completed a pre-post feasibility study of the implementation of a systematic, evidence-based tobacco treatment protocol in an outpatient colorectal surgery clinic. Outcomes included smoking prevalence, pre- and postimplementation smoker identification and intervention rates, recruitment, retention, smoking cessation and provider satisfaction., Results: Preimplementation, 15.5% of 116 surveyed patients were smokers. Fewer than 10% of surveyed patients reported being asked about smoking, and none were offered any cessation intervention. Over a 16-month postimplementation period, 1198 patients were seen on 2103 visits. Of these, 950 (79.3%) patients were asked smoking status on first visit and 1030 (86.0%) were asked on at least 1 visit. Of 169 identified smokers, 99 (58.6%) were referred to follow-up support using an opt-out approach. At 1-, 3- and 6-month follow-up, intention-to-quit rates among 78 enrolled patients were 24.4%, 22.9% and 19.2%, respectively. Postimplementation staff surveys reported that the protocol was easy to use, that staff would use it again and that it had positive patient responses., Conclusion: Implementation of our smoking cessation protocol in an outpatient surgical clinic was found to be feasible and used minimal clinic resources. This protocol could lead to increases in identification and documentation of smoking status, delivery of smoking cessation interventions and rates of smoking reduction and cessation., Competing Interests: None declared., (© 2021 Joule Inc. or its licensors.)

Protein-protein interactions featuring intricate binding epitopes remain challenging targets for synthetic inhibitors. Interactions of NEMO, a scaffolding protein central to NF-κB signaling, exemplify this challenge. Various regulators are known to interact with different coiled coil regions of NEMO, but the topological complexity of this protein has limited inhibitor design. We undertook a comprehensive effort to block the interaction between vFLIP, a Kaposi's sarcoma herpesviral oncoprotein, and NEMO using small molecule screening and rational design. Our efforts reveal that a tertiary protein structure mimic of NEMO is necessary for potent inhibition. The rationally designed mimic engages vFLIP directly causing complex disruption, protein degradation and suppression of NF-κB signaling in primary effusion lymphoma (PEL). NEMO mimic treatment induces cell death and delays tumor growth in a PEL xenograft model. Our studies with this inhibitor reveal the critical nexus of signaling complex stability in the regulation of NF-κB by a viral oncoprotein.

Suicide is a major public health concern. In Canada, suicide is the ninth leading cause of death in all ages, with a rate of 10.3 deaths per 100,000 people. In Nova Scotia, Canada, 137 suicides were reported in 2016 [1]. Suicide risk assessment (SRA) and management are clinical competencies required for patient care. Strategies used for SRA include the use of formal self-report measures [2], personalized clinical interview however vital information about suicide risk may be missed during that unstructured assessment [3] and structured tool to supplement the clinical interview.

The cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene expression to produce an intracellular environment suitable for promoting cell survival and recovery. Posttranscriptional regulatory events are considered as critical mechanisms that modulate core characteristics of mRNA transcripts to promote cell adaptation to various assaults. While the impact of processes such as mRNA splicing, turnover, localization, and translation on the cellular stress response has been extensively studied, recent observations highlight the role of alternative polyadenylation (APA) in response to challenges such as oxidative stress, heat shock, and starvation. The role of APA is comprehensive with far reaching effects on mRNA stability, mRNA localization, and protein coding sequences. Nonetheless, APA remains a relatively unappreciated mode of gene regulation despite its role in regulating key mediators of the stress response. The goal of this review is to provide an overview of the recent advances in our understanding of the various ways by which APA affects cell adaptation to its environment and discuss how a defect in APA could have deleterious consequences on cell survival. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Processing > 3' End Processing., (© 2019 Wiley Periodicals, Inc.)

Activation of AMPK has been associated with pro-atrophic signaling in muscle. However, AMPK also has anti-inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory-driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα-induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A-769662, a specific AMPK activator. AICAR and A-769662 co-treatment was found to be synergistic, suggesting that the anti-cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation-driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Attention-deficit hyperactivity disorder (ADHD) is a neurocognitive disorder characterized by symptoms of inattention, impulsivity and motor hyperactivity. The worldwide prevalence of ADHD, in the general adult population, has been estimated to be 2.8%. Patients with ADHD have a high incidence of comorbidity with other psychiatric disorders. Those with a psychiatric disorder as well as ADHD have more psychosocial difficulties than those without ADHD. Despite knowing that ADHD is often comorbid with other psychiatric diagnoses, there are currently no studies elucidating the prevalence of ADHD in the inpatient psychiatric population, nor is there significant information about its impact. The lack of research into this topic suggests more needs to be done in the field of adult ADHD, especially in the inpatient psychiatric population and with respect to impairment in patient function. Knowing the prevalence of ADHD and its impact on quality of life in adult inpatients will help lay the groundwork for effective screening and management. The purpose of this study was to understand the prevalence rates of ADHD among psychiatric acute care inpatients. Other objectives included comparing the quality of life and functioning between patients with a primary psychiatric diagnosis and ADHD (treated or untreated) versus those with a primary psychiatric diagnosis and no ADHD. Thirty-three (N = 31) psychiatric inpatients were screened using the Adult ADHD Self-Report Scale. Those that screened positive for ADHD received a full diagnostic assessment for ADHD. All patients completed the Weiss Functional Impairment Rating Scale (WFIRS) to assess level of functioning and a Clinical Global Impression of Severity/Improvement Scale (on admission and discharge). Demographic information was also obtained. Of the 31 patients analyzed, 12 had a diagnosis of ADHD (36.4%). The participants diagnosed with ADHD scored significantly higher on the WFIRS, suggesting decreased functioning compared to patients without comorbid ADHD. Patients with ADHD also scored significantly higher in the individual domains of this rating scale, suggesting impairment in family, work and social functioning as well as decreased life-skills, poor self-concept and increased risk-taking behavior. In this sample, the prevalence of ADHD is significantly higher among acute care psychiatric inpatients than in the general population. Patients with concomitant ADHD suffer more functional impairment than those without. These findings merit further investigation into the value of routine screening and patient-specific treatment of ADHD in this patient population.

Cachexia is a deadly muscle wasting syndrome that arises under conditions linked to chronic inflammation, such as cancer. Cytokines, including interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6), and their downstream effectors such as Signal Transducer and Activator of Transcription 3 (STAT3), have been shown to play a prominent role in muscle wasting. Previously, we demonstrated that Pateamine A (PatA), a compound that targets eukaryotic initiation factor 4A (eIF4A), could prevent muscle wasting by modulating the translation of the inducible Nitric Oxide Synthase (iNOS) mRNA. Here we show that hippuristanol, a compound that impedes eIF4A in a manner distinct from PatA, similarly inhibits the iNOS/NO pathway and cytokine-induced muscle wasting. Furthermore, we show that hippuristanol perturbs the activation of the STAT3 pathway and expression of STAT3-gene targets such as IL-6. The decreased activation of STAT3, which resulted from a decrease in STAT3 protein expression, was due to the inhibition of STAT3 translation as there were no changes in STAT3 mRNA levels. These effects are likely dependent on the inhibition of eIF4A activity since we observed similar results using PatA. Our results identify the inhibition of eIF4A-responsive transcripts, such as STAT3, as a viable approach to alleviate cachexia.

Cellular senescence is a physiological response by which an organism halts the proliferation of potentially harmful and damaged cells. However, the accumulation of senescent cells over time can become deleterious leading to diseases and physiological decline. Our data reveal a novel interplay between senescence and the stress response that affects both the progression of senescence and the behavior of senescent cells. We show that constitutive exposure to stress induces the formation of stress granules (SGs) in proliferative and presenescent cells, but not in fully senescent cells. Stress granule assembly alone is sufficient to decrease the number of senescent cells without affecting the expression of bona fide senescence markers. SG-mediated inhibition of senescence is associated with the recruitment of the plasminogen activator inhibitor-1 (PAI-1), a known promoter of senescence, to these entities. PAI-1 localization to SGs increases the translocation of cyclin D1 to the nucleus, promotes RB phosphorylation, and maintains a proliferative, non-senescent state. Together, our data indicate that SGs may be targets of intervention to modulate senescence in order to impair or prevent its deleterious effects., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Hsp90 is a molecular chaperone that protects proteins, including oncogenic signaling complexes, from proteolytic degradation. PU-H71 is a next-generation Hsp90 inhibitor that preferentially targets the functionally distinct pool of Hsp90 present in tumor cells. Tumors that are driven by the MYC oncoprotein may be particularly sensitive to PU-H71 due to the essential role of Hsp90 in the epichaperome, which maintains the malignant phenotype in the setting of MYC. Burkitt lymphoma (BL) is an aggressive B-cell lymphoma characterized by MYC dysregulation. In this study, we evaluated Hsp90 as a potential therapeutic target in BL. We found that primary BL tumors overexpress Hsp90 and that Hsp90 inhibition has antitumor activity in vitro and in vivo , including potent activity in a patient-derived xenograft model of BL. To evaluate the targets of PU-H71 in BL, we performed high-affinity capture followed by proteomic analysis using mass spectrometry. We found that Hsp90 inhibition targets multiple components of PI3K/AKT/mTOR signaling, highlighting the importance of this pathway in BL. Finally, we found that the anti-lymphoma activity of PU-H71 is synergistic with dual PI3K/mTOR inhibition in vitro and in vivo Overall, this work provides support for Hsp90 as a therapeutic target in BL and suggests the potential for combination therapy with PU-H71 and inhibitors of PI3K/mTOR. Mol Cancer Ther; 16(9); 1779-90. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

Strategic change principles are widely cited in business and healthcare management literature, but not in the surgical quality improvement literature despite the need for effective change management skills to successfully enable quality improvement projects. The Ottawa Hospital (TOH) Comprehensive Unit-Based Safety Program (CUSP) model within the Division of General Surgery applied strategic change management principles to support the development and implementation of surgical quality improvement initiatives. Using the TOH CUSP experience, we aim to provide insight and a practical example for surgeons seeking to drive quality improvement within their practice environment.

While flame propagation through obstacles is often associated with turbulence and/or shocks, Bychkov et al. [V. Bychkov et al., Phys. Rev. Lett. 101, 164501 (2008)10.1103/PhysRevLett.101.164501] have revealed a shockless, conceptually laminar mechanism of extremely fast flame acceleration in semiopen obstructed pipes (one end of a pipe is closed; a flame is ignited at the closed end and propagates towards the open one). The acceleration is devoted to a powerful jet flow produced by delayed combustion in the spaces between the obstacles, with turbulence playing only a supplementary role in this process. In the present work, this formulation is extended to pipes with both ends open in order to describe the recent experiments and modeling by Yanez et al. [J. Yanez et al., arXiv:1208.6453] as well as the simulations by Middha and Hansen [P. Middha and O. R. Hansen, Process Safety Prog. 27, 192 (2008)10.1002/prs.10242]. It is demonstrated that flames accelerate strongly in open or vented obstructed pipes and the acceleration mechanism is similar to that in semiopen ones (shockless and laminar), although acceleration is weaker in open pipes. Starting with an inviscid approximation, we subsequently incorporate hydraulic resistance (viscous forces) into the analysis for the sake of comparing its role to that of a jet flow driving acceleration. It is shown that hydraulic resistance is actually not required to drive flame acceleration. In contrast, this is a supplementary effect, which moderates acceleration. On the other hand, viscous forces are nevertheless an important effect because they are responsible for the initial delay occurring before the flame acceleration onset, which is observed in the experiments and simulations. Accounting for this effect provides good agreement between the experiments, modeling, and the present theory.

During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs) and are translated several times more efficiently than unspliced mRNAs that have the same sequence but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during HSV infection, cells were transfected with plasmids harboring an unspliced renilla luciferase (RLuc) reporter mRNA or RLuc constructs with introns near the 5' or 3' end of the gene. After splicing of intron-containing transcripts, all three RLuc mRNAs had the same primary sequence. Upon infection in the presence of actinomycin D, spliced mRNAs were much less sensitive to degradation by copies of Vhs from infecting virions than were unspliced mRNAs. During productive infections (in the absence of drugs), RLuc was expressed at substantially higher levels from spliced than from unspliced mRNAs. Interestingly, the stimulatory effect of splicing on RLuc expression was significantly greater in infected than in uninfected cells. The translational stimulatory effect of an intron during HSV-1 infections could be replicated by artificially tethering various EJC components to an unspliced RLuc transcript. Thus, the splicing history of an mRNA, and the consequent presence or absence of EJCs, affects its level of translation and sensitivity to Vhs cleavage during lytic HSV infections., Importance: Most mammalian mRNAs are spliced. In contrast, of the more than 80 mRNAs harbored by herpes simplex virus 1 (HSV-1), only 5 are spliced. In addition, synthesis of the immediate early protein ICP27 causes partial inhibition of pre-mRNA splicing, with the resultant accumulation of both spliced and unspliced versions of some mRNAs in the cytoplasm. A common perception is that HSV-1 infection necessarily inhibits the expression of spliced mRNAs. In contrast, this study demonstrates two instances in which pre-mRNA splicing actually enhances the synthesis of proteins from mRNAs during HSV-1 infections. Specifically, splicing stabilized an mRNA against degradation by copies of the Vhs endoribonuclease from infecting virions and greatly enhanced the amount of protein synthesized from spliced mRNAs at late times after infection. The data suggest that splicing, and the resultant presence of exon junction complexes on an mRNA, may play an important role in gene expression during HSV-1 infections., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention., Methods: Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors' Continuous Performance Test to assess attention., Results: A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG., Conclusions: Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: This study applies the updated HIV-Associated Neurocognitive Disorders (HAND) diagnostic algorithm., Methods: Participants were 210 HIV-infected-adults, classified using proposed HAND criteria: HIV-Associated Dementia (HAD), Mild Neurocognitive Disorder (MND), Asymptomatic Neurocognitive Impairment (ANI)., Results: The algorithm yielded: normal = 32.8%, ANI = 21.4%, MND = 34.3%, and HAD = 11.4%. Normal participants performed superior to HAND-defined participants on cognition, and HAD participants performed more poorly on global cognition and executive functioning. Two distinct subgroups of interest emerged: (1) functional decline without cognitive impairment; (2) severe cognitive impairment and minimal functional compromise., Conclusions: The algorithm discriminates between HIV-infected cognitively impaired individuals. Diagnosis yields two unique profiles requiring further investigation. Findings largely support the algorithm's utility for diagnosing HIV-cognitive-impairment, but suggest distinct subsets of individuals with discrepant cognitive/functional performances that may not be readily apparent by conventional application of HAND diagnosis.

Objective: To examine meal preparation ability after right or left hemisphere damage (RHD, LHD) caused by stroke and whether cognitive (spatial abilities, aphasia, limb apraxia) and motor deficits are differentially associated with meal preparation., Design: Observational cohort design., Setting: Primary care Veterans Affair Medical Center and private medical center., Participants: Volunteer right-handed sample of adults with LHD (n=30) or RHD (n=16) caused by stroke and healthy demographically matched adults (n=63) (N=109)., Interventions: Not applicable., Main Outcome Measures: Total completion time, number and type of errors, and level of independence for a meal preparation task consisting of making a hot beverage and toast, eating part of the meal, and clean-up., Results: Both stroke groups took significantly more time to complete the meal preparation task than the control group. Total errors and level of independence were worse in the group with LHD than other groups, but individual errors did not significantly differ between the 2 stroke groups. While correlations should be interpreted cautiously, especially in the relatively small RHD group, poorer ipsilesional motor performance was associated with longer completion time in the RHD group, and poorer contralesional motor performance and greater aphasia were associated with less independence in the LHD group., Conclusions: These findings demonstrate impaired meal preparation after LHD or RHD but greater impairment after LHD. Poorer meal preparation is associated with different cognitive and motor deficits in the 2 stroke groups., (Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Poole JL, Sadek J, Haaland KY. Ipsilateral deficits in 1-handed shoe tying after left or right hemisphere stroke., Objective: To examine 1-handed shoe tying performance and whether cognitive deficits more associated with left or right hemisphere damage differentially affect it after unilateral stroke., Design: Observational cohort comparing ipsilesional shoe tying, spatial and language skills, and limb praxis., Setting: Primary care Veterans Affairs and private medical center., Interventions: Not applicable., Participants: Volunteer right-handed sample of adults with left or right hemisphere damage and healthy demographically matched adults., Main Outcome Measure: The number of correct trials and the total time to complete 10 trials tying a shoe using the 1-handed method., Results: Both stroke groups had fewer correct trials and were significantly slower tying the shoe than the control group. Spatial skills predicted accuracy and speed after right hemisphere damage. After left hemisphere damage, accuracy was predicted by spatial skills and limb praxis, while speed was predicted by limb praxis only., Conclusions: Ipsilesional shoe tying is similarly impaired after left or right hemisphere damage, but for different reasons. Spatial deficits had a greater influence after right hemisphere damage, and limb apraxia had a greater influence after left hemisphere damage. Language deficits did not affect performance, indicating that aphasia does not preclude using this therapy approach. These results suggest that rehabilitation professionals should consider assessment of limb apraxia and ipsilesional skill training in the performance of everyday tasks.

We have recently shown ipsilateral dynamic deficits in trajectory control are present in left hemisphere damaged (LHD) patients with paresis, as evidenced by impaired modulation of torque amplitude as response amplitude increases. The purpose of the current study is to determine if these ipsilateral deficits are more common with contralateral hemiparesis and greater damage to the motor system, as evidenced by structural imaging. Three groups of right-handed subjects (healthy controls, LHD stroke patients with and without upper extremity paresis) performed single-joint elbow movements of varying amplitudes with their left arm in the left hemispace. Only the paretic group demonstrated dynamic deficits characterized by decreased modulation of peak torque (reflected by peak acceleration changes) as response amplitude increased. These results could not be attributed to lesion volume or peak velocity as neither variable differed across the groups. However, the paretic group had damage to a larger number of areas within the motor system than the non-paretic group suggesting that such damage increases the probability of ipsilesional deficits in dynamic control for modulating torque amplitude after left hemisphere damage.

Objectives: There are conflicting data on cancer incidence and mortality in psychiatric patients, although most studies suggest that while cancer mortality is higher, incidence is no different from that in the general population. Different methodologies and outcomes may account for some of the conflicting results. We investigated the association between mental illness and cancer incidence, first admission rates, and mortality in Nova Scotia using a standard methodology., Method: A population-based record-linkage study of 247,344 patients in contact with primary care or specialist mental health services during 1995 to 2001 was used. Records were linked with cancer registrations and death records., Results: Cancer mortality was 72% higher in males (95%CI, 63% to 82%) and 59% higher in females (95%CI, 49% to 69%) among patients in contact with mental health services. This was reflected in similarly elevated first admission rates. However, there was weaker and less consistent evidence for increased incidence. For several cancer sites, incidence rate ratios were lower than might be expected given the mortality and first admission rate ratios, and no higher than that of the general population. These were melanoma, prostate, bladder, and colorectal cancers in males., Conclusion: People with mental illness in Nova Scotia have increased mortality from cancer, which cannot always be explained by increased incidence. Possible explanations for further study include delays in detection or initial presentation leading to more advanced staging at diagnosis, and difficulties in communication or access to health care.