bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sources of electrophysiological variability in the retina ofPeriplaneta americana
Authors: Frolov Roman V. 
Published: March 2019

AbstractVariability in the electrophysiological properties of homotypic photoreceptors is widespread and is thought to facilitate functioning under disparate illumination conditions. Compound eyes of insects have three sources of variability: inter-individual, intra-individual, and intra-ommatidial, the latter two overlapping. Here, I explored the causes of variability inPeriplaneta americana, a nocturnal insect characterized by highly variable photoreceptor responses. By recording from photoreceptors in dissociated ommatidia, including consecutive recordings from photoreceptors in the same ommatidium (SO), I studied the variability of six properties: whole-cell membrane capacitance (Cm), phototransduction latency, maximal conductance (Gmax) and the slope factor of the sustained Kv current, absolute sensitivity in dim light, and sustained light-induced current (LIC) amplitude in bright light. Coefficient of variation (CV) metrics were used to compare variances in four experimental groups: SO, same animal (SA), all data combined “full sample” (FS), and full sample of all SO recordings (FSSO). For the normally distributed parametersCm,Gmax, slope factor, and latency, the highest CV values were found in FS and FSSO, intermediate in SA, and the lowest in SO. On average, SO variance accounted for 47% of the full-sample variance in these four parameters. Absolute sensitivity and LIC values were not normally distributed, and the differences in variability between SO and FS/FSSO groups were smaller than for the other four parameters. These results indicate two main sources of variability, intra-ommatidial and inter-individual. Inter-individual variability was investigated by exposing adult cockroaches to constant light or dark for several months. In both groups, the majority of CV measures for the six parameters decreased compared to control, indicating substantial contribution of phenotypic plasticity to inter-individual differences. Analysis of variability of resting potential and elementary voltage responses revealed that resting potential is mainly determined by the sustained Kv conductance, whereas voltage bump amplitude is mainly determined by current bump amplitude andCm.
12 Impact of Aripiprazole Long-acting Injectable (ALAI) Initiation on Hospitalizations and Visits to Emergency
Authors: Parro-Torres Carlos , Ros-Cucurull Elena , Arques-Egea Sergio 
Published: March 2019

AbstractBackgroundAripiprazole once-monthly is an LAI formulation of aripiprazole that is currently approved in the USA and Europe for the treatment of schizophrenia. Some studies have reported a decline in hospital admissions and emergency use after initiation on long-acting injectable (LAI) antipsychotics, but the effects of using recently commercialised LAI aripiprazole remains uncertain.AimsTo characterize the impact of ALAI initiation on number of hospitalizations and visits to the emergency service, among patients suffering from schizophrenia attending regularly to psychiatric consultations of Gregorio Marañón University General Hospital (Madrid, Spain).MethodsPatients initiated on (ALAI) were studied in an observational mirror-image design to assess changes in number of hospitalizations and visits to the emergency service in the 12months pre- vs 12months post-depot initiation. Other sociodemographic, physical and clinical variables such as age, gender, weight, blood pressure and presence of dual disorders were also gathered. Variables were collected reviewing clinical records.Wilcoxon test was used to assess hospitalizations and visits to the emergency. Paired t-tests were used to assess changes in weight and blood pressure. Non parametric Mann-Whitney U test was used to compare aripiprazole doses between genders and in order to assess de influence of dual disorders. In order to perform the statistical analysis, IBM SPSS statistics v.20 was used.Results31 patients were included in the final analysis. Mean age was 44.67 (SD=15.57) years. Most of the patients were male (54.8% vs 45.2%). 71% were previously receiving oral antipsychotics treatment, whereas 29% were receiving other LAI antipsychotic: no significant differences were observed when comparing hospitalizations (p=0.74) or emergency use (p=0.98) in the 12months post-initiation between these groups. Mean dosage was 352.67mg/28days (SD=0.461), and 38.7% needed an adjustment during the first year of treatment (dosage increased in 76.9%). A combination of two or more antipsychotics was prescribed in 64.5% of the patients. Mean psychiatric number of hospitalizations a year declined from 0.483/year pre-initiation to 0.224/year post-initiation (P<0.05), whereas mean visits a year to the emergency psychiatric service declined from 1.419 pre-initiation to 1.032 post-initiation (P<0.1). No significant changes in weight (p=0.82), systolic (p=0.56) or diastolic (p=0.29) blood pressure were observed. No gender differences in dosage were observed (p=0.246). Suffering from dual disorders had no influence on dosage either (p=0.68).ConclusionsLAI aripiprazole initiation appears to provide a benefit decreasing hospitalization needs and emergency services consumption and it was well tolerated. This data supports previous evidence indicating superiority of LAI antipsychotics.
20 The Need for Speed: Adjunctive Triple Chronotherapy in the Accelerated Treatment of Acute Depression and Suicidality in the Adolescent Population
Authors: Hurd Diane , Arzubi Eric , Herrera Mariela Rojas , Coombs Nicholas , Brant Jeannine 
Published: March 2019

AbstractObjectiveThis pilot study aims to explore the feasibility and proof of concept of triple chronotherapy (TCT) as a non-pharmacological, adjunctive intervention in the treatment of acute depression and suicidality in the adolescent population.MethodThirty-one adolescents with moderate to severe depression were included in the study. Each participant underwent a 4-day intervention (TCT) which consisted of one night of sleep deprivation followed by three days of sleep phase advancement and daily bright light therapy. Primary outcomes were feasibility and depression, as measured by Hamilton Depression Scale-17 (HAMD-17) scores. Secondary outcomes included severity of illness, anxiety, self-harm, insomnia, and suicidality.ResultsTwenty-nine (94%) adolescents completed the TCT protocol. Twenty-six (84%) of the 31 enrolled patients experienced a reduction in depressive symptoms of at least 50% from baseline; 24 (77%) achieved remission, defined as a HAMD-17 score less than 8. Secondary outcomes showed significant improvement following the 4-day TCT intervention; improvement was sustained through the 7–10 day and 1-month follow-up periods.ConclusionThis pilot study determined TCT to be a feasible, safe, accelerated, and promising adjunctive treatment for acute depression in the adolescent population. This study has been submitted for publication and is currently under review.
22 Using Light to Unveil Depression: The Role of Optogenetics
Authors: Diniz Aurelio Lourenco , Escobar-Montealegre Freddy , Peçanha Marcela Pellegrini 
Published: March 2019

AbstractIntroductionMajor depressive disorder (MDD) is a highly prevalent and often debilitating condition with a vast impact on modern societies worldwide. Although it interferes significantly with functioning, MDD is frequently unresponsive to conventional treatment approaches and pharmacotherapy failure has been reported in approximately one third of patients. Current knowledge of the exact underlying disease mechanisms is insufficient, and may thus largely contribute to such therapeutic limitations. Optogenetics, a novel study field employing the expression of genetically-encodable light-sensitive proteins in specific cell types, circumvents the limitations of other forms of neuromodulation and enables temporally precise, bidirectional control of cellular activity in well-defined neuronal populations. This strategy has been used successfully to dissect neural pathways and circuitries involved in complex mental diseases such as MDD.MethodsA systematic literature search was conducted using the terms “Optogenetics”, “Depression” and “Major depressive disorder” on the databases MEDLINE, LILACS, SciELO, Pubmed and BIREME. Inclusion criteria were adopted: articles published in the English language from 1971 (description of bacteriorhodopsin as a light-activated regulator of transmembrane ion flow) to 2017 and articles based on experimental studies were selected.ResultsBy using highly validated animal models based on the exposure of phenotypically susceptible rodents to different forms of chronic stress, researchers have been able to reproduce the hallmark symptoms of Depression as well as the histopathological abnormalities found in human brain specimens post-mortem. Several brain regions and neuron populations involved in MDD have been identified by use of a variety of molecular resources including viral vectors, genetically engineered animals, multiple promoters and bacterial opsins. Important areas of dysfunction underlying depression including the medial prefrontal cortex, the ventral tegmental area, the nucleus accumbens, the hippocampus and the basolateral amygdala have been investigated by using optogenetic neuromodulation, yielding new insights into the pathological processes underlying MDD. Researchers have been able to pinpoint affected circuitries and employ time-precise light modulation to successfully revert symptoms of MDD, restoring normal function. It is important to highlight that although promising, studies using optogenetics are controversial, largely due to the variable set tools, models and tests employed in research.ConclusionLight modulation using optogenetics has greatly aided to establish accurate models to unveil the neurobiological basis of Depression. Further research will continue to help build more complete pathophysiological constructs and pave the way for new treatment strategies.
27 A New Method for Initiating Treatment with the Long-acting Antipsychotic Aripiprazole Lauroxil
Authors: Meyer Jonathan , Jain Rakesh , Wehr Angela , Rege Bhaskar , von Moltke Lisa , Weiden Peter J 
Published: March 2019

AbstractSTUDY OBJECTIVESlow release is a fundamental feature of long-acting injectable (LAI) antipsychotics. This property allows continuous drug exposure between dosing intervals. However, there can be a significant delay between giving the first LAI dose and achievement of efficacious plasma concentrations. This time period requires additional pharmacologic intervention. Until now, this delay was addressed with one of two strategies: 1) continuing with supplemental oral antipsychotic, or 2) giving more LAI up front (e.g. loading dose). A third strategy has now been developed to reduce the time needed for oral supplementation when starting the LAI aripiprazole lauroxil (AL) from 21days to 1day. A nano-crystalline milled dispersion of AL (ALNCD; brand name ARISTADA INITIO™) was formulated by reducing the AL particle diameter from micron-size particles to nanometer- sized particles. ALNCD has faster dissolution and a shorter half-life than AL and is designed to be used as a single injection along with a single oral aripiprazole dose of 30mg as a 1-day alternative to the 21days of oral aripiprazole supplementation. Here we provide an overview of the new 1-day initiation regimen for starting AL treatment, and demonstrate the relative contributions of each of its components.METHODSA blinded, randomized, phase 1, pharmacokinetic (PK), and safety study compared the 1-day initiation regimen with the 21-day oral aripiprazole regimen. A combination of observed data, and population pharmacokinetic model–based simulations were used to plot plasma aripiprazole concentrations of single doses of ALNCD, 30mg oral aripiprazole, and AL, individually, and all three combined.RESULTSThe PK profiles of the 1-day and 21-day initiation regimens (both in conjunction with either 441mg or 882mg doses of AL) were comparable, with therapeutically relevant aripiprazole levels achieved within 4days of treatment initiation. The safety profile of the 1-day initiation regimen was similar to the 21-day initiation regimen, and consistent with that of AL. Aripiprazole concentration–time profiles demonstrated that each component delivered aripiprazole to the systemic circulation at different time periods, with the 30mg dose of oral aripiprazole predominant in the first week, followed by ALNCD, and then AL.CONCLUSIONSThe 1-day initiation regimen is well-tolerated and a suitable alternative to 21days of oral aripiprazole supplementation for starting AL. Each component of the 1-day initiation regimen, together with AL, is necessary to provide continuous coverage from treatment initiation until the next regularly scheduled AL injection.Funding Acknowledgements: This study was funded by Alkermes Inc.
36 Too Scared to Blink: Pseudoparkinsonism due to Nyctophobia
Authors: Janjua Khurram , Hirsch Alan R. 
Published: March 2019

AbstractIntroductionA hallmark of Parkinson’s disease is facial akinesia with decrease in blink frequency (Karson, 1984). A markedly decreased blink frequency from nyctophobia, a fear of the dark, has not heretofore been reported.MethodCase Study: A 26-year-old right handed male presented with a 20-year history of phantasmagoria. Visual hallucinations of strangers appeared several to a hundred times a day, seconds to minutes in duration. These morbid images were horrific, of dead people or ghosts, suddenly appearing in his visual space, actively attacking real people. Examples included a little girl, decapitated, cradling her head in her arm or Freddy Krueger like apparitions, shooting, stabbing, strangling or maiming actual people who were within the patient’s visual field. He was able to differentiate between the hallucinations and real people, either from the context (a non hallucination would not be murdering someone else), or he would wait for the hallucinations to vanish, allowing him to then interact with the person who is actually there. The images were so disturbing to him that he fled his home state to run away from the hallucinations, but to his chagrin, they persisted. There were diurnal variations to his hallucinations, which were more frequent at night, or when he closed his eyes, and the fear of these has induced nyctophobia. In order to avoid these, he attempted to curtail closing his eyes or blinking. He had been treated with 9 different psychotropic medications, which had no effect on his hallucinations. Phenytoin was begun, and once therapeutic levels were achieved, all of his hallucinations resolved, as did his nyctophobia, with return to normal blink frequency.ResultsPhysical examination: Bilateral palmar erythema. Facial expression with decreased blink frequency, approximately 1/per minute, but not otherwise hypomimetic. Neurological examination: Cranial Nerve (CN) Examination: CN III, IV and VI: bilateral ptosis. Motor Examination: Normal tone without cogwheel rigidity. No bradykinesia. Drift Testing: Right upward-outward drift, right cerebellar spooning, and Abductor Digiti Minimi sign. Gait: Normal without instability or retropulsion. Reflexes: 1+ throughout. Hoffman Reflex: positive bilaterally. Other: Magnetic Resonance Imaging of brain with/without infusion: Normal. Five-day Electroencephalogram: Temporal Lobe Status Epilepticus with bilateral foci.DiscussionIn this individual, the sheer terror of phantasmagoria with his eyes closed, forced him to maintain them in the open position as long as possible, reducing his blink frequency to once a minute or less. The return to a normal rate of blink frequency with treatment using phenytoin, with resolution of his horrific hallucinations, further validates this as the origin for his infrequent blinking. In those with low nictation, without other manifestations of Parkinson’s disease, query as to volitional inhibition of blink frequency and nyctophobia is warranted.
50 Adjunctive Buprenorphine/Samidorphan Combination in Patients with Major Depressive Disorder: Phase 3 Long-term Extension Study Results
Authors: Thase Michael , Stanford Arielle D. , Memisoglu Asli , Martin William , Claxton Amy , Bodnik J. Alexander , Trivedi Madhukar H. , Fava Maurizio , Pathak Sanjeev 
Published: March 2019

AbstractIntroductionBuprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2Study Objective(s)1. To characterize the safety profile following long-term treatment with BUP/SAM2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAMMethodsFORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).ResultsOf 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.ConclusionsLong-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.Funding Acknowledgements: Alkermes, Inc.
58 Case Report: Clinical Challenges in the Diagnoses and Management of Delirious Mania in a US Veteran with a Mental Health History of Bipolar Disorder
Authors: Zaidi Muhammad , Brown Kurt , Brown Aquanette , Neptune Dominique , Perkins Vicenzio-Holder 
Published: March 2019

AbstractA 46 year old Caucasian male veteran with a mental health history of Bipolar Disorder was admitted to the inpatient psychiatric unit following an episode of mania. He was re-started on his outpatient medication regimen for mood stabilization with Quetiapine, Lamotrigine, and Clonazepam. He improved initially, however, on hospital Day 3, the veteran was noted to have acute worsening of manic and psychotic symptoms including, decreased need for sleep, excess energy and responding to internal stimuli. Additionally, he developed symptoms which were atypical for mania, including unprovoked agitation, depersonalization, difficulty sustaining attention, and visual hallucinations. These mental status changes were associated with, excessive motor movement, walking with bizarre postures, squatting, laying taut on the ground, and standing still for several minutes in uncomfortable positions. At this time, Seroquel was switched with Olanzapine for management of mania and psychosis. On physical exam, his vital signs were notable for tachycardia and fever, his extremities were noted to have a normal range of motion; he also experienced loss of bowel continence. The treatment team initiated a medical work up for delirium which revealed no infectious, neurological, or metabolic cause. Of note, there was concern for benzodiazepine withdrawal; however, adequate management did not relieve the symptoms. The veteran was transferred to medicine and neurology was consulted to assist with medical workup. His neuroleptic and benzodiazepine medications were discontinued at that time, except for Lamotrigine. The veteran was then transferred back to psychiatry after medical stabilization, Lamotrigine was discontinued at that time. He was started on Haloperidol, Benztropine and restarted on Clonazepam. At this time, veteran experienced improvement on his mental status exam, with resolution of mania, psychosis, and delirium. However, after two days of treatment, he developed acute rigidity in his extremities. Intramuscular Benztropine and Lorazepam improved his rigidity. Haloperidol was discontinued because of side effects and the veteran was managed with Risperidone and Ativan. He continued to show improvement in his mental status examination and was discharged on a medication regimen of Risperidone, Clonazepam, and Benztropine. The veteran experienced signs and symptoms which were atypical in nature for Bipolar Mania, such as fever, movement disorder, and delirium. This presentation is consistent with a rare medical condition, Delirious Mania for which limited research is available. Delirious mania meets the criteria for mania and delirium with out an underlying medical disorder. Delirious mania is a potentially life threatening but under-recognized neuropsychiatric syndrome. Early recognition and aggressive treatment can significantly reduce morbidity and mortality.