Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy.

Myotonic dystrophy (DM) is caused by expansions of C(C)TG repeats in the non-coding regions of the DMPK and CNBP genes, and DM patients often suffer from sudden cardiac death due to lethal conduction block or arrhythmia. Specific molecular changes that underlie DM cardiac pathology have been linked to repeat-associated depletion of Muscleblind-like (MBNL) 1 and 2 proteins and upregulation of CUGBP, Elav-like family member 1 (CELF1). Hypothesis solely targeting MBNL1 or CELF1 pathways that could address all the consequences of repeat expansion in heart remained inconclusive, particularly when the direct cause of mortality and results of transcriptome analyses remained undetermined in Mbnl compound knockout (KO) mice with cardiac phenotypes. Here, we develop Myh6-Cre double KO (DKO) (Mbnl1-/-; Mbnl2cond/cond; Myh6-Cre+/-) mice to eliminate Mbnl1/2 in cardiomyocytes and observe spontaneous lethal cardiac events under no anesthesia. RNA sequencing recapitulates DM heart spliceopathy and shows gene expression changes that were previously undescribed in DM heart studies. Notably, immunoblotting reveals a nearly 6-fold increase of Calsequestrin 1 and 50% reduction of epidermal growth factor proteins. Our findings demonstrate that complete ablation of MBNL1/2 in cardiomyocytes is essential for generating sudden death due to lethal cardiac rhythms and reveal potential mechanisms for DM heart pathogenesis.

A Myotonic Dystrophy Type I patient with Predominant Proximal Muscle Weakness without Action Myotonia- A Case Report and Review of Pathology.

PURPOSE: Early distal muscle weakness and myotonia are typical clinical presentations in type I myotonic dystrophy (DM1). We present a DM1 case with unusual predominant proximal weakness without action myotonia. CASE REPORT: The chief complaint of this 48-year-old female was difficulty in raising her arms and frequent falling in recent years. On neurological examination, proximal muscle weakness was more pronounced than the distal muscle groups, in addition to facial involvement. Although she did not experience any action myotonia throughout her life, hand and tongue myotonia were readily inducible by percussion during neurological examination. The diagnosis of DM1 was later supported by electromyography and neuropathological studies, and confirmed by molecular testing. The pathological findings in this patient and the characteristic features in typical DM1 patients were briefly reviewed. CONCLUSION: The unusual presentation of this DM1 patient suggests the importance of comprehensive neurological examination including percussion of thenar and tongue muscles, even in a patient with atypical distribution of muscle weakness and without a clear personal and family history of myotonia. In addition to molecular testing, muscle biopsy remains supportive in making the diagnosis.

Association between Pre-Existing Coronary Artery Disease and 5-Year Mortality in Stroke Patients with High-Grade Carotid Artery Stenosis.

BACKGROUND: The coincidence of coronary artery disease (CAD) and carotid artery stenosis (CAS) was observed. However, the association between pre-existing CAD and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between pre-existing CAD and outcomes of acute IS patients with high-grade CAS. METHODS: From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between patients with and without pre-existing CAD. RESULTS: Among 372 individuals, 75 (20.2%) patients had pre-existing CAD and 297 (79.8%) patients did not have pre-existing CAD. The prevalence rates of hypertension, congestive heart failure, chronic kidney disease, and gout in patients with pre-existing CAD were significantly higher than in those without pre-existing CAD (p = 0.017, p < 0.001, p = 0.002, and p < 0.001, respectively). The multivariate Cox proportional hazards model revealed that pre-existing CAD was a significant risk factor for a 5-year all-cause mortality in acute IS patients with high-grade CAS (hazard ratio = 2.26; 95% confidence interval = 1.35-3.79; p = 0.002). CONCLUSION: Pre-existing CAD was associated with an increased risk of 5-year mortality in acute IS patients with high-grade CAS. Intensive treatment for the pre-existing CAD may reduce long-term mortality in acute IS patients with high-grade CAS.

Concomitant Guillain-Barré Syndrome and Acute Transverse Myelitis in an Older Adult-A Case Report.

PURPOSE: Guillain-Barré syndrome concomitant with spinal cord involvement, which is defined as Guillain-Barré syndrome and acute transverse myelitis overlap syndrome, is rarely seen in the elders. Here we present a 68-year-old female patient who developed Guillain-Barré syndrome, as well as acute transverse myelitis at the same episode. CASE REPORT: This patient developed acute weakness of lower limbs, which then rapidly became tetraplegia and hyporeflexia within 5 days. She also had impaired pinprick and vibration sensations below T4, as well as urinary and defecation incontinence. The nerve conduction studies revealed a motorsensory axonal neuropathy. Cerebrospinal fluid analysis showed albuminocytological dissociation and elevated IgG index. The spinal magnetic resonance imaging study revealed heterogeneously contrastenhanced, long-segmental intramedullary lesion from C2 to T3. Other laboratory findings, including blood anti-aquaporin 4 antibody, were not remarkable. The patient's tetraplegia was gradually improved by plasmapheresis and methylprednisolone pulse therapy. CONCLUSION: Although Guillain-Barré syndrome and acute transverse myelitis overlap syndrome is occasionally seen in young adults, it could still occur in the elderly patients. Plasmapheresis and steroid pulse therapy could be beneficial to improve functional outcome of patients with this immunemediated neurological disease.

Evaluation of remediation process with soapberry derived saponin for removal of heavy metals from contaminated soils in Hai-Pu, Taiwan.

The use of a biodegradable natural plant-based surfactant extracted from soapberry is proposed for the remediation of Ni, Cr and Mn from industrial soil site in Hai-Pu, Taiwan. Batch experiments were performed under variation of fundamental factors (saponin concentration, pH, and incubation time) for metal remediation. Removal of Ni and Mn were increased with increasing saponin concentration (0.015-0.150 g/L), whereas the removal of Cr was increased upto 0.075 g/L saponin. The Ni, Cr and Mn were removed significantly (p < or = 0.05) at near to the neutral and slightly acidic (pH 5 to 8) conditions. Removal efficiency of Ni (99%) from the soil was found to be greater than that of Cr (73%) or Mn (25%) in the presence of saponin at a concentration of 0.150 g/L at pH 5. The removal percentage increased with incubation time where the removal of Ni was faster than that of Cr and Mn. The result indicates the feasibility of eco-friendly removal of heavy metal (Ni, Cr and Mn) from industrial soil by soil washing process in presence of plant derived saponin.

Removal of Cu, Pb and Zn by foam fractionation and a soil washing process from contaminated industrial soils using soapberry-derived saponin: a comparative effectiveness assessment.

The feasibility of using the eco-friendly biodegradable surfactant saponin (a plant-based surfactant) from soapberry and surfactin from Bacillus subtilis (BBK006) for the removal of heavy metals from contaminated industrial soil (6511mgkg(-1) copper, 4955mgkg(-1) lead, and 15090mgkg(-1) zinc) by foam fractionation and a soil flushing process was evaluated under variation of fundamental factors (surfactant concentration, pH, temperature and time). The results of latter process showed that 1-2% Pb, 16-17% Cu and 21-24% Zn was removed by surfactin after 48h, whereas the removal of Pb, Cu and Zn was increased from 40% to 47%, 30% to 36% and 16% to 18% in presence of saponin with an increase from 24 to 72h at room temperature by the soil washing process at pH 4. In the foam fractionation process, the metal removal efficiencies were increased with increases in the saponin concentration (0.075-0.15gL(-1)) and time (24-72h), whereas the efficiency was decreased with increasing pH (4-10) and temperature (>40°C). The removal efficiencies of Pb, Cu and Zn were increased significantly from 57% to 98%, 85% to 95% and 55% to 56% with an increase in the flow rate from 0.2 to 1.0Lmin(-1) at 0.15gL(-1) saponin (pH 4 and 30°C). The present investigation indicated that the foam fractionation process is more efficient for the removal of heavy metal from contaminated industrial soil in comparison to the soil washing process. The plant-based eco-friendly biodegradable biosurfactant saponin can be used for environmental cleanup and pollution management.

Attenuation of estradiol on the reduction of striatal dopamine by amphetamine in ovariectomized rats.

Amphetamine (AMPH) is a highly addictive drug of abuse which exhibits toxicity to dopaminergic neurons in long-term abusers. Estrogen seems to show neuroprotection in dopamine (DA) deficit caused by AMPH. The present study was to investigate the effects of estradiol on the levels of striatal DA in ovariectomized (Ovx) rats treated with or without AMPH. Female rats were Ovx for 2 weeks before administration of AMPH (5 mg/kg/day, i.p.) with or without 17beta-estradiol benzoate (EB) (25 microg/kg/day, s.c.) for 7 days. The striatal tissues were collected, homogenized with DA mobile phase, and centrifuged. The concentrations of DA in the supernatants were detected by HPLC. The protein expressions of dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT-2), and tyrosine hydroxylase (TH) were analyzed by Western blotting. The results indicated that AMPH could attenuate DA level significantly in striatum (P < 0.01). Comparing to control groups, administration of either EB or EB plus AMPH increased DA level (P < 0.01). The protein expression of striatal DAT was significant greater (P < 0.01) in rats treated with AMPH plus EB than AMPH treated animals. These results suggest that the DA levels in striatum can be enhanced by EB via an increase of DAT expression following administration of AMPH.