Psychopathy and Occurrence of Gambling Problems: The Role of Gambling Protective Strategies and Urgency.

BACKGROUND: Psychopathy has been an increasing area of clinical and personality research and is associated with numerous problematic outcomes, including pathological gambling, though this area of research is limited. The most common conceptualization of psychopathy is a two-factor model of primary and secondary psychopathy, with primary psychopathy comprising more interpersonal traits and secondary psychopathy encompassing more antisocial behaviors. Previous research has linked psychopathy to greater urgency and lower utilization of harm reduction strategies. OBJECTIVES: The current study examines the relationship between primary psychopathy, secondary psychopathy, and problematic gambling, as well as the possible mechanisms of these relationships. METHOD: College student gamblers (n = 308) completed surveys on psychopathy, impulsivity, protective behavioral strategies regarding gambling, and possible gambling problems. RESULTS: Primary psychopathy was inversely related to gambling protective behavioral strategies (PBS) and secondary psychopathy was positively associated with higher levels of urgency. Secondary psychopathy, via urgency, was a strong predictor of whether an individual will experience gambling problems, while primary psychopathy via PBS better predicts the number of gambling problems one experiences. CONCLUSION: This study extends an overall under-researched area of gambling and personality and highlights the importance of delineating different factors of psychopathy regarding problematic gambling outcomes.

Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry.

Early prediction of whether a liver allograft will be utilized for transplantation may allow better resource deployment during donor management and improve organ allocation. The national donor management goals (DMG) registry contains critical care data collected during donor management. We developed a machine learning model to predict transplantation of a liver graft based on data from the DMG registry. METHODS: Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12-18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. RESULTS: Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. CONCLUSIONS: This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.

Symptomatic Presentation of Acute Myocardial Infarction in Heart Transplantation Patients.

Patients with acute myocardial infarction with a history of an orthotopic heart transplantation rarely present with classic anginal symptoms, secondary to cardiac denervation. We present 2 cases, the first of a patient with a ST-segment elevation myocardial infarction and the second who presented with a non-ST-segment elevation myocardial infarction. Both patients presented with typical symptoms and were treated with percutaneous coronary intervention. (Level of Difficulty: Intermediate.).

Anion Exchange Doping: Tuning Equilibrium to Increase Doping Efficiency in Semiconducting Polymers.

High electron affinity (EA) molecules p-type dope low ionization energy (IE) polymers, resulting in an equilibrium doping level based on the energetic driving force (IE-EA), reorganization energy, and dopant concentration. Anion exchange doping (AED) is a process whereby the dopant anion is exchanged with a stable ion from an electrolyte. We show that the AED level can be predicted using an isotherm equilibrium model. The exchange of the dopant anion (FeCl3-) for a bis(trifluoromethanesulfonamide) (TFSI-) anion in the polymers poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly[3-(2,2-bithien-5-yl)-2,5-bis(2-hexyldecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione-6,5-diyl] (PDPP-2T) highlights two cases in which the process is nonspontaneous and spontaneous, respectively. For P3HT, FeCl3 provides a high doping level but an unstable counterion, so exchange results in an air stable counterion with a marginal increase in doping. For PDPP-2T, FeCl3 is a weak dopant, but the exchange of FeCl3- for TFSI- is spontaneous, so the doping level increases by >10× with AED.

Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily targets the respiratory system. This study describes the characteristics associated with mortality among patients infected with SARS-CoV-2 at a single hospital in Baguio City, Philippines. METHODS: We reviewed medical records (including history, laboratory results and treatment regimen) of 280 confirmed COVID-19 patients admitted to a single hospital during March-October 2020. Clinical characteristics and outcomes (frequency and type of complication, recovery rate and mortality) were evaluated. Multiple logistic regression was used to analyse factors associated with mortality. RESULTS: The mean age of COVID-19 patients was 48.4 years and the female-to-male ratio was 1.8:1. Hypertension, cardiovascular disease (CVD) and diabetes were the most frequent comorbidities reported. Common presenting symptoms were respiratory and constitutional, with 41% of patients not reporting symptoms on admission. Patients with moderate, severe and critical disease comprised 45%, 8% and 4%, respectively. A total of 15% had complications, health care-associated pneumonia being the most frequent complication. The recovery rate was 95%; 5% of patients died, with multiorgan failure being the most common cause. The presence of CVD, chronic kidney disease, prolonged prothrombin time and elevated lactate dehydrogenase (LDH) were associated with mortality. DISCUSSION: Most COVID-19 patients in our population had asymptomatic to moderate disease on admission. Mortality from COVID-19 was associated with having CVD, chronic kidney disease, elevated LDH and prolonged prothrombin time. Based on these results, we emphasize that people should take all necessary precautions to avoid infection with SARS-CoV-2.

System-Level Variation in Multiple Sclerosis Disease-Modifying Therapy Utilization: Findings From the Multiple Sclerosis Continuous Quality Improvement Research Collaborative.

BACKGROUND: The Multiple Sclerosis Continuous Quality Improvement (MS-CQI) Collaborative is the first multicenter improvement research collaborative for multiple sclerosis (MS). The main objective of this study is to describe baseline system-level variation in disease-modifying therapy (DMT) utilization across 4 MS centers participating in MS-CQI. METHODS: Electronic health record data from the first year of the 3-year MS-CQI study were analyzed. Participants were adults ≥ 18 years with MS presenting to any of the 4 MS-CQI centers. DMT utilization was categorized into oral, infusion, and injection types. Multinomial logistic regression was used to investigate associations between centers and DMT utilization. RESULTS: Overall, 2,029 patients were included in the analysis. Of those patients, 75.1% were female, mean age was 50 years, and 87.4% had relapsing-remitting MS. Overall, 32.7% were on an oral DMT, 23.5% on an infusion DMT, and 43.9% on an injection DMT. Overall, statistically significant differences (p < 0.01) were observed across centers for proportions of patients who received oral, infusion, and no DMTs. There were also overall significant differences (p < 0.01) across MS types for proportions of encounters who received oral, infusion, injection, no DMTs, and mean age varied significantly across centers. CONCLUSION: System-level effects on MS treatment and outcomes have not been previously studied and our findings contribute initial evidence concerning system-level variation in DMT utilization. Results suggest system-level variation in DMT utilization (ie, after adjusting for individual level factors, MS center or location of care a person with MS engages in care influences DMT treatment choices), resulting in a lack of standardization in DMT management. Continued research and improvement efforts targeting system-level performance could improve outcomes for people with MS.

Protective Behavioral Strategies Moderate the Association between Narcissistic Traits and Alcohol Pathology in College Student Drinkers.

BACKGROUND: Personality traits found in Cluster B personality disorders have garnered considerable empirical attention and have been linked to a litany of issues, such as alcohol-related problems. While psychopathic traits have been linked to alcohol-use consequences, narcissistic traits remain understudied. OBJECTIVES: The current study examines the relationship between narcissistic traits and alcohol use and consequences as a function of Protective Behavioral Strategies (PBS) in a sample of college students. METHOD: Participants (n = 387 college student drinkers; 69.25% female) completed a series of questionnaires assessing alcohol use and consequences, PBS use, and narcissistic traits. RESULTS: There was a significant positive association between narcissistic traits and alcohol use and consequences. The interaction of PBS and narcissistic traits was also statistically significant. Simple slopes revealed that at high levels of PBS (+1SD), the relationship between narcissistic traits and alcohol-use consequences was attenuated and not significant, while at low levels of PBS (-1SD), this association was potentiated. CONCLUSION: These findings suggest that interventions targeting PBS use may be one way to reduce alcohol problems among those with higher levels of narcissistic traits.

Should I stay or should I go? Approach/avoidance conflict and emotional functioning.

Personality has long held a prevalent place in the pantheon of psychological research. In the last 40 years, neuropsychological models of personality have become a popular predictor of human behaviour and emotionality. With a particular focus on Gray's Reinforcement Sensitivity Theory, this study investigated the interaction of high Behavioural Activation System (BAS) and Behavioural Inhibition System (BIS) as a predictor of emotional functioning. Participants (n = 499) recruited from the community completed an online survey composed of questions on demographic information, behavioural inhibition and activation, emotional instability and indices of depression, anxiety and mixed depression-anxiety. Consistent with our primary hypothesis, the interaction of high BAS × BIS predicted emotional instability using an observed variable path model. This was subsequently associated with depression, anxiety and mixed depression-anxiety symptoms. Future avenues for research using BIS/BAS monitoring in clinical practice and study limitations are discussed. © 2018 John Wiley & Sons, Ltd.

Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across a Human Blood-Brain Barrier Model.

The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones; hence, leptin must be transported through the blood-brain barrier (BBB) to reach its target sites in the central nervous system. During obesity, however, leptin BBB transport is decreased, in part precluding leptin as a viable clinical therapy against obesity. Although the short isoform of the ObR (ObRa) has been implicated in the transport of leptin across the BBB as a result of its elevated expression in cerebral microvessels, accumulating evidence indicates that leptin BBB transport is independent of ObRa. In the present study, we employed an ObR-neutralising antibody (9F8) to directly examine the involvement of endothelial ObR in leptin transport across an in vitro human BBB model composed of the human endothelial cell line hCMEC/D3. Our results indicate that, although leptin transport across the endothelial monolayer was nonparacellular, and energy- and endocytosis-dependent, it was not inhibited by pre-treatment with 9F8, despite the ability of the latter to recognise hCMEC/D3-expressed ObR, prevent leptin-ObR binding and inhibit leptin-induced signal transducer and activator of transcription 3 (STAT-3) phosphorylation in hCMEC/D3 cells. Furthermore, hCMEC/D3 cells expressed the transporter protein low-density lipoprotein receptor-related protein-2 (LRP-2), which is capable of binding and endocytosing leptin. In conclusion, our results demonstrate that leptin binding to and signalling through ObR is not required for efficient transport across human endothelial monolayers, indicating that ObR is not the primary leptin transporter at the human BBB, a role which may fall upon LRP-2. A deeper understanding of leptin BBB transport will help clarify the exact causes for leptin resistance seen in obesity and aid in the development of more efficient BBB-penetrating leptin analogues.

Cortical Lewy bodies and Aß burden are associated with prevalence and timing of dementia in Lewy body diseases.

AIMS: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. METHODS: One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aß plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. RESULTS: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aß plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions. CONCLUSIONS: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aß plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele.

Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that has been shown to have anti-inflammatory and matrix metalloproteinase (MMP) inhibitor properties. PPARγ agonists have been shown to have neuroprotective effects in various neurodegeneration models where inflammation is implicated, including models of Parkinson's disease. However, no studies have looked at the effects of partial PPARγ agonists. EXPERIMENTAL APPROACH: The neuroprotective effects of the PPARγ full agonist, pioglitazone (20 mg/kg), partial PPARγ agonist GW855266X (15 mg/kg) and PPAR-δ full agonist GW610742X (10 mg/kg) were investigated in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease when administered prior to or post 6-OHDA lesioning. The integrity of the nigrostriatal system was assessed by assessing the numbers dopaminergic neurons in the substantia nigra (SN) and by assessing striatal dopamine content. The degree of microglia activation in the SN was also immunohistochemistry assessed utilizing the marker OX-6 for activated microglia and CD-68 a marker for phagocytic microglia. Additionally we performed immunocytochemistry for MMP3 in the SN. Finally, we investigated whether a period of drug withdrawal for a further 7 days affected the neuroprotection produced by the PPARγ agonists. KEY RESULTS: Both pioglitazone and GW855266X protected against 6-OHDA induced loss of dopaminergic neurons in the substantia nigra and depletion of striatal dopamine when administered orally twice daily for either 1) 7 day prior to and 7 days post lesioning or 2) for 7 days starting 2 days post lesioning when neurons will be severely traumatized. 6-OHDA lesioning was associated with an increase in microglia activation and in numbers of MMP-3 immunoreactive cells which was attenuated by pioglitazone and GW855266X. Neuroprotective effects were not replicated using the PPARδ agonist GW610742X. Subsequent withdrawal of both pioglitazone and GW855266X, for a further 7 days negated any neuroprotective effect suggesting that long-term administration may be required to attenuate the inflammatory response. CONCLUSIONS AND IMPLICATIONS: For the first time a partial PPAR-γ agonist has been shown to be neuroprotectory when administered post lesioning in a parkinsonian model. Effects may be via the inhibition of microglial and MMP activation and support further research.

Chelating agents for neurodegenerative diseases.

It has become apparent in the last years that metal ion homeostasis and its dysfunction which results in increased accumulation in brain, notably of copper, iron and zinc, may be associated with a number of neurodegenerative diseases, such that chelation therapy may be one therapeutic option. We briefly outline chelators currently available together with strategies to develop new chelators capable of crossing the blood-brain-barrier. The homeostasis of iron in brain together with changes in brain iron with ageing are reviewed as well as the role of iron in Parkinson's disease, and the potential of chelation therapy in PD. Copper and zinc homeostasis in brain and age associated changes are then outlined, along with a discussion of the possible involvement of Zn, Cu and Fe in Alzheimer's disease. We conclude with a brief summary of chelation therapy in AD.

Left subclavian artery coverage during TEVAR: is revascularization necessary?

Thoracic endovascular aortic repair (TEVAR) has rapidly become a viable and accepted treatment option for atherosclerotic aortic aneurysms as well as a variety of other aortic pathologies including ulcers, dissection, coarctation and disruption. Left subclavian artery (LSA) coverage is often necessary to achieve proximal seal in up to 40% of patients treated with TEVAR. The management of the LSA in this cohort of patients remains controversial. Studies in support of routine pre-operative LSA revascularization show that coverage of the LSA during TEVAR is associated with an increased risk of stroke, paraplegia and arm ischemia. Other studies show that intentional coverage of the LSA without revascularization is not associated with increased morbidity and lends support to those who advocate more selective LSA revascularization during TEVAR (i.e. in those patients with patent LIMA-coronary bypass, dominant or isolated left vertebral artery, or a functioning left upper extremity (LUE) dialysis arteriovenous fistula). This paper is intended to review the literature comparing routine and selective LSA revascularization after TEVAR to determine the best management strategy.

Complications of endovenous lasers.

Endovenous laser ablation (EVLA) and radiofrequencey ablation have become the procedures of choice for the treatment of superficial venous insufficiency. Their minimally invasive technique and safety profile when compared with operative saphenectomy have led to this change. As EVLA has replaced saphenectomy as the procedure of choice, the distribution of complications has changed. We evaluated the most common and most devastating complications in the literature including burns, nerve injury, arterio-venous fistula (AVF), endothermal heat-induced thrombosis and deep venous thrombosis. The following review will discuss the most frequently encountered complications of treatment of superficial venous insufficiency using EVLA. The majority of the complications described can be avoided with the use of good surgical technique and appropriate duplex ultrasound guidance. Overall, EVLA has an excellent safety profile and should be considered among the first line for treatment of superficial venous reflux.

Update on the Amplatzer duct occluder: a 10-year experience in Asia.

Few data exist regarding the efficacy and safety of the Amplatzer ductal occluder (ADO) type 1 device in the Asian region. This retrospective study, conducted between August 2001 and April 2011, attempted device placement for 231 patients (165 females and 66 males) with a median age of 7.4 years (range, 3 months to 64 years) and an average weight of 19.4 kg (range, 4.1-81.0 kg). Among the patients in this study, 66 (28.6%) had pulmonary hypertension, ten (4.3%) had trisomy 21, and eight (3.5%) had other congenital cardiac anomalies. The mean narrowest patent ductus arteriosus (PDA) diameter was 4.2 mm (range, 1.3-10 mm), and the ampulla size was 9.6 mm (range, 4-20 mm). Successful implantation was achieved for 229 patients (99.1%). Complete angiographic occlusion was achieved for 201 patients (87.8%) at the end the procedure. Follow-up data were available for 129 patients (66%). At the follow-up assessment, complete echocardiographic occlusion was seen in 128 patients (99.2%) after 1 month and in 100% of the patients after 6 months. The significant morbidities involved one device embolization and one dislodgment, for which surgical retrieval was performed. No mortalities occurred during the study period, and no late clinical adverse events occurred during the follow-up period. Occlusion of the PDA using ADO is safe, effective, and applicable for a wide range of PDA sizes including large PDAs in small symptomatic infants and in adults. Good outcomes can be attributed to experience of the operators, proper patient selection, and appropriate device size selection.

Successful hybrid stage I palliation for hypoplastic left heart syndrome in a developing nation.

The first successful stage I palliation for hypoplastic left heart syndrome (HLHS) in a four-day-old female in the Philippines is reported, along with a discussion of the particular dynamics and challenges of performing this kind of surgery in a developing nation. Challenges met were not limited to the preoperative and perioperative period but involved the interstage period as well. In the face of such challenges, our experience, reported here, is the cause for cautious optimism.

Nitric oxide is involved in the response of the isolated intact and epithelium-denuded rat trachea to the ß2 adrenergic receptor agonist salbutamol.

BACKGROUND: The involvement of the airway smooth muscle mediator nitric oxide (NO) in the actions of the ß2 agonist salbutamol (Sal), a well-known bronchodilator, is very poorly understood. OBJECTIVES: To determine if endogenous NO release is a major factor in the Sal-induced relaxation of the carbachol- and electrical field-stimulated rat trachea and determine the role of the tracheal epithelium as the possible source of NO involved in these effects. METHODS: Isolated carbachol- or electric field-stimulated pre-contracted in vitro male Sprague Dawley rat tracheas (with epithelium intact or denuded) were relaxed with incremental or discrete concentrations of Sal in the presence and absence of the NO synthesis inhibitor L-NAME. RESULTS: Epithelium-denuded tracheas showed a reduced relaxation response to Sal. L-NAME (1 mM) similarly decreased the sensitivity of the rat tracheas to Sal in both epithelium-intact and -denuded conditions. In the presence of L-NAME, high concentrations of Sal induced an unexpectedly large relaxation response in carbachol-stimulated rat tracheas with both intact and denuded epithelium. Sal relaxation was also affected by L-NAME in electrical field-stimulated epithelium-intact and -denuded tracheas. CONCLUSION: The results suggest that NO derived from sources other than the epithelium is an important mediator of the Sal-induced relaxation in rat tracheas.

Regional distribution of clomipramine and desmethylclomipramine in rat brain and peripheral organs on chronic clomipramine administration.

The tricyclic antidepressant (TCA) clomipramine has been widely used in psychiatry for over 40 years. More recently, its therapeutic potential as an antineoplastic drug has been identified. However, there are no prior data on regional distribution in the brain of clomipramine and its primary metabolite (desmethylclomipramine) after chronic oral administration. The aim of this study was to determine the concentrations of clomipramine and desmethylclomipramine in different rat-brain regions and to compare those with levels in plasma and peripheral organs after chronic oral treatment of Sprague Dawley rats (15 mg/kg) for 14 days. The levels of both parent TCA and metabolite were analysed by high-performance liquid chromatography in six brain regions (cortex, hypothalamus, hippocampus, striatum, brainstem and cerebellum), five peripheral organs and in plasma. Our data show that the cerebral cortex had the highest concentration of clomipramine (2.9 microg/mg), with successively lower concentrations in the hypothalamus, striatum, cerebellum, hippocampus and brainstem. Of the peripheral organs, the lungs and liver, had the highest levels of clomipramine, while in the heart, only the metabolite was detected. The plasma concentration (0.17 microg/ml or 0.48 microM) was comparable to that in the hippocampus and cerebellum (approximately 0.20 microg/mg). The differential distribution of clomipramine in different brain regions and the regional variation in clomipramine to desmethylclomipramine ratios have implications for the use of clomipramine in psychiatry and neuro-oncology.