Regulation of the sphingolipid signaling pathways in the growing and hypoxic rat heart

Sphingolipids (SLs) have a biomodulatory role in physiological as well as pathological cardiovascular conditions. This study aims to assess the variation of SL mediators and metabolizing enzymes in the growing and hypoxic rat heart. Sprague-Dawley rats were placed in a hypoxic environment at birth. Control animals remained in room air. In control animals, activities of acidic-sphingomyelinase (A-SMase), sphingomyelin synthase (SMS), glucosylceramide synthase (GCS), and ceramidase decreased with age in both ventricles whereas activity of neutral-sphingomyelinase (N-SMase) increased with age. Hypoxic RV mass was 171 and 229% that of controls, at 4 and 8 weeks, respectively. This was accompanied by an increase in RV myocardial ceramide synthesis, consumption and breakdown, with a net effect of suppression of ceramide accumulation and increase in diacylglycerol (DAG) concentration. In addition, significant increase in activities of: A-SMase by 26 and 29%, SMS by 108 and 40%, and ceramidase by 66 and 35%, in the hypoxic RV rats as compared to controls, was noted at 4 and 8 weeks of age, respectively. Sphingolipids and their regulating enzymes appear to play a role in adaptive responses to chronic hypoxia in the neonatal rat heart.     

Investigation of impact loading rate effects on the ligamentous cervical spinal load-partitioning using finite element model of functional spinal unit C2–C3

The cervical spine functions as a complex mechanism that responds to sudden loading in a unique manner, due to intricate structural features and kinematics. The spinal load-sharing under pure compression and sagittal flexion/extension at two different impact rates were compared using a bio-fidelic finite element (FE) model of the ligamentous cervical functional spinal unit (FSU) C2–C3. This model was developed using a comprehensive and realistic geometry of spinal components and material laws that include strain rate dependency, bone fracture, and ligament failure. The range of motion, contact pressure in facet joints, failure forces in ligaments were compared to experimental findings. The model demonstrated that resistance of spinal components to impact load is dependent on loading rate and direction. For the loads applied, stress increased with loading rate in all spinal components, and was concentrated in the outer intervertebral disc (IVD), regions of ligaments to bone attachment, and in the cancellous bone of the facet joints. The highest stress in ligaments was found in capsular ligament (CL) in all cases. Intradiscal pressure (IDP) in the nucleus was affected by loading rate change. It increased under compression/flexion but decreased under extension. Contact pressure in the facet joints showed less variation under compression, but increased significantly under flexion/extension particularly under extension. Cancellous bone of the facet joints region was the only component fractured and fracture occurred under extension at both rates. The cervical ligaments were the primary load-bearing component followed by the IVD, endplates and cancellous bone; however, the latter was the most vulnerable to extension as it fractured at low energy impact.     

Comparative study of growth temperature impact on the susceptibility of biofilm-detached and planktonic Staphylococcus aureus cells to benzalkonium chloride

The present study investigated and compared the effect of growth temperature on the susceptibility of biofilm-detached and planktonic Staphylococcus aureus cells, to benzalkonium chloride (BAC). This study also highlights the impact of BAC on the bacterial physiology and the role of membrane fluidity regulation as a bacterial resistance mechanism. The minimum inhibitory concentration of BAC was characterized with micro-dilution growth inhibition assay. The BAC treatment was performed on S. aureus cultured at 20 °C and 37 °C, for 24 h. The morphology of S. aureus cells was examined using scanning electron microscopy. The loss of bacterial membrane integrity after BAC treatment was studied by monitoring the intracellular potassium ion leakage using the atomic absorption spectroscopy. The bacterial membrane total fatty acid composition, controlling the membrane fluidity, was analyzed by GC/MS. The results showed that the resistance of S. aureus cells to BAC increased with the increase of growth temperature. The planktonic cells were more susceptible to BAC than biofilm-detached ones. The rise of growth temperature resulted in an increase of S. aureus membrane rigidity. Furthermore, a higher membrane fluidity was observed in planktonic cells when compared to that in the biofilm-detached ones. The resistance of S. aureus seems to depend on the growth temperature. Compared to planktonic cells, biofilm-detached cells showed a greater resistance to BAC. The BAC targets and disturbs the bacterial membrane. Membrane fluidity modulation is likely a one of resistance mechanisms for S. aureus to BAC at the cellular scale. Therefore, disinfection procedures, in food sector, should be adapted for bacteria detached from biofilm.     

Dysphagia in Acute Stroke: Incidence,Burden and Impact on Clinical Outcome

Background

Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke.

Methods

We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia.

Results

Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality.

Conclusion

Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.     

Single argonaute protein from Toxoplasma gondii is involved in the double-stranded RNA induced gene silencing

Here, we report the characterization of the argonaute protein from Toxoplasma gondii. This is the first report on the function of an argonaute protein with structural features overlapping between argonaute proteins of archaeal bacteria and eukaryotes. The full-length cDNA clone has an open reading frame of 1575 bp, which encodes a 524 amino acid protein with a calculated molecular weight of 58.5 kDa and an estimated isoelectric point of 9.4. This argonaute protein, called TgAgo, exhibits unique features: (i) TgAgo is smaller than reported argonaute proteins derived from higher eukaryotic organisms (i.e. Arabidopsis, human and nematodes) but has a similar size to those from archaeal bacteria (i.e. Pyrococcus furiosus and Archaeoglobus fulgidus); (ii) TgAgo contains a conserved PIWI domain and non-conserved PAZ domain; (iii) TgAgo is mainly localized in the cytoplasm; and (iv) despite its small size, TgAgo participates in the double-stranded RNA induced gene silencing. Using a transgenic parasite line, in which TgAgo expression is lowered, we showed that the expression of TgAgo is required for the double-stranded RNA induced gene silencing, RNA interference mechanism.     

Alzheimer disease periventricular white matter lesions exhibit specific proteomic profile alterations

The white matter (WM) represents approximately half the cerebrum volume and is profoundly affected in Alzheimer’s disease (AD). However, both the WM responses to AD as well as potential influences of this compartment to dementia pathogenesis remain comparatively neglected. Neuroimaging studies have revealed WM alterations are commonly associated with AD and renewed interest in examining the pathologic basis and importance of these changes.     

Levels of Heavy Metals and Essential Minerals in Hair Samples of Children with Autism in Oman: a Case–Control Study

Toxic levels of heavy metals and low levels of essential minerals have been suggested to play a critical role in the pathogenesis of autism spectrum disorders (ASD). This study documents the levels of heavy metals and essential minerals in hair samples of children with ASD in Muscat, the urbanized capital of Oman, Muscat. The study included 27 children with ASD and 27 matched non-ASD controls. Parental interviews were held and dietary intake questionnaires completed in conjunction with the collection of hair samples. Analysis of heavy metals and essential minerals was carried out by inductively coupled plasma mass spectrometry. Chi-square analysis and non-parametric Fisher’s exact tests were used to assess statistical significance. Children with ASD had significantly higher levels of all 11 analyzed heavy metals in their hair samples (P?<?0.05), ranging from 150 to 365 % of control levels. ASD children also had significantly higher levels of essential minerals sulfur, sodium, magnesium, potassium, zinc, and iron, but lower levels of calcium and copper in their hair samples. This study corroborates data from previous studies in different parts of the world indicating the presence of elevated levels of heavy metals and selective depletion of essential minerals in the hair of children with ASD.     

De Novo Mutations in SIK1 Cause a Spectrum of Developmental Epilepsies

Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. Here we report six unrelated individuals with mutations in salt-inducible kinase 1 (SIK1) in a series of 101 persons with early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Individuals with SIK1 mutations had short survival in cases with neonatal epilepsy onset, and an autism plus developmental syndrome after infantile spasms in others. All six mutations occurred outside the kinase domain of SIK1 and each of the mutants displayed autophosphorylation and kinase activity toward HDAC5. Three mutations generated truncated forms of SIK1 that were resistant to degradation and also showed changes in sub-cellular localization compared to wild-type SIK1. We also report the human neuropathologic examination of SIK1-related developmental epilepsy, with normal neuronal morphology and lamination but abnormal SIK1 protein cellular localization. Therefore, these results expand the genetic etiologies of developmental epilepsies by demonstrating SIK1 mutations as a cause of severe developmental epilepsy.