The Effect of Zinc on L-leucine Transport in Lobster Intestine

The current study is a characterization of L-leucine absorption across the American lobster intestine in order to determine the likelihood of a bis-complex formation with zinc ([Leu]-Zn-[Leu]) as a possible substrate for PEPT1. This study required isolated lobster intestines to be mounted in a perfusion chamber in order to quantify 3H-L-leucine transport. It was hypothesized that an apical dipeptide transporter, PEPT1, was responsible for uptake of L-leucine via formation of a bis-complex with zinc ([Leu]-Zn-[Leu]) in the form of molecular mimicry, where the bis-complex mimics the normal dipeptide substrate of the proposed carrier system. It was found that L-leucine transport across the lobster intestine was significantly stimulated by luminal zinc and other cations and that this stimulation led to enhanced net flux of the amino acid across the intestine compared to its net flux in the absence of these cations. Transmural transport ofL-leucine was also significantly stimulated by a variety of organic solutes including L-histidine, L-cysteine, and glycylsarcosine (GLY-SAR) by way of countertransport. While many observations in the present study suggest that PEPT1 may be the carrier system responsible for transmural leucine transport in the presence of zinc, other cation-dependent carrier systems, such as the B^0 transporter, with strong transstimulation properties, may also be a suitable candidate for leucine transport in the lobster intestine

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease : a randomised controlled trial

Background Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Electrocardiogram and cardiac testing among patients in the emergency department with seizure versus syncope

Objective Cardiogenic syncope can present as a seizure. The distinction between seizure disorder and cardiogenic syncope can only be made if one considers the diagnosis. Our main objective was to identify whether patients presenting with a chief complaint (reason for visit) as seizure or syncope received an electrocardiogram in the emergency department across all age groups. Methods We conducted a secondary analysis of data collected in the 2010 to 2014 National Hospital Ambulatory Medical Care Survey comparing patients presenting with a chief complaint of syncope versus seizure to determine likelihood of getting an evaluation for possible life threatening cardiovascular disease. The primary endpoint was receiving an electrocardiogram in the emergency department; secondary endpoint was receiving cardiac biomarkers. Results There was a total of 144,094 patient encounters. Of these visits, 1,553 had syncope and 1,470 had seizure (60.3% vs. 44.2% female, 19.9% vs. 29.0% non-white). After adjusting for age, sex, mode of arrival and insurance, patients with syncope were more likely to receive an electrocardiogram compared to patients with seizure (odds ratio, 10.86; 95% confidence interval [CI], 8.52 to 13.84). This was true across all age groups (0 to 18 years, 56% vs. 7.5%; 18 to 44 years, 60% vs. 27%; 45 to 64 years, 82% vs. 41%; ≥65 years, 85% vs. 68%; P<0.01 for all). Car- diac biomarkers were also obtained more frequently in adult patients with syncope patients (18 to 44 years, 17.5% vs. 10.5%; 45 to 64 years, 33.8% vs. 21.4%; ≥65 years, 47.1% vs. 32.3%; P<0.01 for all). Conclusion Patients evaluated in the emergency department for syncope received an electrocar- diogram and cardiac biomarkers more frequently than those that had seizure

Electrocardiogram and cardiac testing among patients in the emergency department with seizure versus syncope.

OBJECTIVE: Cardiogenic syncope can present as a seizure. The distinction between seizure disorder and cardiogenic syncope can only be made if one considers the diagnosis. Our main objective was to identify whether patients presenting with a chief complaint (reason for visit) as seizure or syncope received an electrocardiogram in the emergency department across all age groups. METHODS: We conducted a secondary analysis of data collected in the 2010 to 2014 National Hospital Ambulatory Medical Care Survey comparing patients presenting with a chief complaint of syncope versus seizure to determine likelihood of getting an evaluation for possible life threatening cardiovascular disease. The primary endpoint was receiving an electrocardiogram in the emergency department; secondary endpoint was receiving cardiac biomarkers. RESULTS: There was a total of 144,094 patient encounters. Of these visits, 1,553 had syncope and 1,470 had seizure (60.3% vs. 44.2% female, 19.9% vs. 29.0% non-white). After adjusting for age, sex, mode of arrival and insurance, patients with syncope were more likely to receive an electrocardiogram compared to patients with seizure (odds ratio, 10.86; 95% confidence interval [CI], 8.52 to 13.84). This was true across all age groups (0 to 18 years, 56% vs. 7.5%; 18 to 44 years, 60% vs. 27%; 45 to 64 years, 82% vs. 41%; ≥65 years, 85% vs. 68%; P\u3c0.01 for all). Car- diac biomarkers were also obtained more frequently in adult patients with syncope patients (18 to 44 years, 17.5% vs. 10.5%; 45 to 64 years, 33.8% vs. 21.4%; ≥65 years, 47.1% vs. 32.3%; P\u3c0.01 for all). CONCLUSION: Patients evaluated in the emergency department for syncope received an electrocar- diogram and cardiac biomarkers more frequently than those that had seizure

Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys:Virtual dissection with probabilistic DTI tractography

It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390–396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390–396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients