Pigment-dispersing factor and CCHamide1 in the Drosophila circadian clock network.

Animals possess a circadian central clock in the brain, where circadian behavioural rhythms are generated. In the fruit fly (Drosophila melanogaster), the central clock comprises a network of approximately 150 clock neurons, which is important for the maintenance of a coherent and robust rhythm. Several neuropeptides involved in the network have been identified, including Pigment-dispersing factor (PDF) and CCHamide1 (CCHa1) neuropeptides. PDF signals bidirectionally to CCHa1-positive clock neurons; thus, the clock neuron groups expressing PDF and CCHa1 interact reciprocally. However, the role of these interactions in molecular and behavioural rhythms remains elusive. In this study, we generated Pdf 01 and CCHa1SK8 double mutants and examined their locomotor activity-related rhythms. The single mutants of Pdf 01 or CCHa1SK8 displayed free-running rhythms under constant dark conditions, whereas approximately 98% of the double mutants were arrhythmic. In light-dark conditions, the evening activity of the double mutants was phase-advanced compared with that of the single mutants. In contrast, both the single and double mutants had diminished morning activity. These results suggest that the effects of the double mutation varied in behavioural parameters. The double and triple mutants of per 01, Pdf 01, and CCHa1SK8 further revealed that PDF signalling plays a role in the suppression of activity during the daytime under a clock-less background. Our results provide insights into the interactions between PDF and CCHa1 signalling and their roles in activity rhythms.

Recovery From Severe Systemic Peripheral Neuropathy Secondary to Erythropoietic Protoporphyria by Liver Transplant: A Case Report.

Erythropoietic protoporphyria is a rare inherited metabolic disorder involving the heme biosynthesis pathway and leads to the accumulation of protoporphyrin in the erythrocytes or liver. Although peripheral neuropathy is known to develop occasionally in other types of porphyria, it rarely occurs in patients with erythropoietic protoporphyria. A 16-year-old boy was transferred to our hospital due to end-stage liver disease secondary to erythropoietic protoporphyria. Severe systemic peripheral neuropathy, similar to that presented in Guillain-Barré syndrome, developed; it was promptly managed with mechanical ventilation. Electrophysiological assessment of the presented neuropathy showed no responsiveness, indicating severe axonopathy. Six weeks after the transfer, liver transplant was performed.Postoperatively, hepatorenal syndromes improved immediately, and his erythrocyte protoporphyrin level decreased from 6291 to 174 µg/dL red blood cells.The patient started to move his limbs gradually and was weaned from mechanical ventilation 2 months after liver transplant. Eventually, he was discharged from hospital and was able to ambulate with assistance 10 months after liver transplant. To our knowledge, this is the first report detailing the clinical course in a patient with erythropoietic protoporphyria who recovered from severe systemic peripheral neuropathy after liver transplant.

Ten-Year Evaluation of the TOYOTA Prehospital Stroke Scale for Tissue Plasminogen Activator Intravenous Therapy in the Real World.

BACKGROUND: Emergency medical services are an important part of acute stroke management. We devised a prehospital stroke scale, the TOYOTA prehospital stroke scale for tissue plasminogen activator (t-PA) intravenous therapy (TOPSPIN) for triaging patients with ischemic stroke and especial indications for intravenous t-PA therapy in December 2006; this scale comprises 5 items including consciousness, atrial fibrillation, language disorder, disturbance of the upper extremities, and disturbance of the lower extremities. The aim of this study was to analyze the results of 10 years of TOPSPIN implementation and to distinguish ischemic stroke from hemorrhagic stroke in the real world. METHODS: We prospectively enrolled consecutive patients who were transferred to our hospital and evaluated by Toyota city ambulance services using the TOPSPIN from December 2006 to January 2017. We examined definite diagnosis at the time of hospital discharge (ischemic stroke, hemorrhagic stroke, or stroke mimic), positive-predictive value of the stroke, the rate of the recanalization therapy, and clinical differentiation among patients with hemorrhagic stroke, ischemic stroke, and stroke mimics. RESULTS: A total of 1,482 consecutive patients were enrolled; 1,134 (76.5%) were patients with stroke (628 ischemic-type, 34 transient ischemic attack-type, and 472 hemorrhagic-type) and 348 (23.5%) without stroke (80 with seizure, 42 with syncope, 27 with hypoglycemia, and 199 other). Among 628 patients with ischemic stroke, 130 (20.7%) received intravenous recombinant t-PA treatment, endovascular therapy, or both. The presence of atrial fibrillation, older age, lower blood pressure, and lower total TOPSPIN score was more commonly associated with ischemic stroke than with hemorrhagic stroke. In multivariable logistic regression analysis, the presence of atrial fibrillation was independently associated with ischemic stroke (OR 2.33; 95% CI 1.61-3.40). CONCLUSIONS: The TOPSPIN is a simple prehospital stroke scale that includes an assessment of atrial fibrillation. Detection of atrial fibrillation in the prehospital stage may point to a higher probability of ischemic stroke.

Familial Pernicious Chronic Intestinal Pseudo-obstruction with a Mitochondrial DNA A3243G Mutation.

We report the case of a mother and two children who shared a mitochondrial DNA A3243G mutation. The mother had diabetes mellitus, neurogenic bladder, bradykinesia, dystonia, and slowly progressive cerebellar ataxia. Her two daughters were diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes at adolescence. They all presented with gastrointestinal symptoms at an advanced clinical stage. They were diagnosed with chronic intestinal pseudo-obstruction, and they were resistant to therapy. The mother and her youngest daughter died from aspiration pneumonia because of vomiting. The determination of chronic intestinal pseudo-obstruction is an important prognostic factor in patients with the mitochondrial DNA A3243G variant.

A case of intracranial arterial dolichoectasia with 4 repeated cerebral infarctions in 6 months and enlargement of basilar artery.

A 78-year-old man was admitted to our hospital because of sudden right hemiparesis and dysarthria. His cranial MRI showed an area of hyperintensity in left pons on DWI and MRA revealed dilated, elongated and tortuous intracranial artery. We diagnosed as acute phase ischemic stroke and intracranial arterial dolichoectasia (IADE). Intravenous infusion of rt-PA was performed 157 minutes after the onset of symptoms, and his hemiparesis improved. However, he subsequently suffered from cerebral infarction 4 times in 6 months, and we treated him twice with thrombolytic therapy. Although thrombolytic therapy was effective in the short term and antithrombotic therapy was continued, he had bilateral hemiplegia and severe dysphagia because of repeated cerebral infarctions. Hence basilar artery was dilated with intramural hemorrhage over 6 months, and we discontinued antithrombolytic therapy. It is possible that antithrombolytic therapy affects enlargement of IADE. Antithrombolytic therapy for IADE should be done carefully.