Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation

We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion–plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns.     

The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain. These viruses demonstrated reduced pathogenicity after intra-cranial infection as well, indicating a decrease in neurovirulence. Intra-nasal inoculation or inoculation by scarification with a low dose of recombinant virus containing a deletion of the entire N-terminal domain of E3L protected against challenge with a high dose of wild-type vaccinia virus, suggesting that this replication competent, but attenuated strain of vaccinia virus may have promise as an improved vaccine for protecting against smallpox, and as a vector for inducing mucosal immunity to heterologous pathogenic organisms.     

Synergistic inhibition of PARP‐1 and NF‐κB signaling downregulates immune response against recombinant AAV2 vectors during hepatic gene therapy

Host immune response remains a key obstacle to widespread application of adeno‐associated virus (AAV) based gene therapy. Thus, targeted inhibition of the signaling pathways that trigger such immune responses will be beneficial. Previous studies have reported that DNA damage response proteins such as poly(ADP‐ribose) polymerase‐1 (PARP‐1) negatively affect the integration of AAV in the host genome. However, the role of PARP‐1 in regulating AAV transduction and the immune response against these vectors has not been elucidated. In this study, we demonstrate that repression of PARP‐1 improves the transduction of single‐stranded AAV vectors both in vitro (～174%) and in vivo (two‐ to 3.4‐fold). Inhibition of PARP‐1, also significantly downregulated the expression of several proinflammatory and cytokine markers such as TLRs, ILs, NF‐κB subunit proteins associated with the host innate response against self‐complementary AAV2 vectors. The suppression of the inflammatory response targeted against these vectors was more effective upon combined inhibition of PARP‐1 and NF‐κB signaling. This strategy also effectively attenuated the AAV capsid‐specific cytotoxic T‐cell response, with minimal effect on vector transduction, as demonstrated in normal C57BL/6 and hemophilia B mice. These data suggest that targeting specific host cellular proteins could be useful to attenuate the immune barriers to AAV‐mediated gene therapy.     

Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum-graecum) in Response to Carbendazim

Fenugreek (Trigonella foenum-graecum) is an annual herb, used as a spice and traditionally as medicine. Fenugreek finds its uses in treating hyperglycemia, hyperlipidemia and disorders of gastro-intestinal and cardiovascular systems. Fenugreek cultivation in India is affected by fungal diseases like root-rot and damping-off and fungicides like carbendazim are used to overcome these infections. Fungicides play both positive and negative role in plants; fungicides protect plants from diseases and also exert oxidative stress simultaneously. This report is on the response of antioxidants, superoxide dismutase and catalase in fenugreek seeds and plants treated to different concentrations of carbendazim.     

Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats

Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to increased risk of diseases. Oxidative stress is considered as a major risk factor and contributes to age related increase in DNA oxidation and DNA protein cross-links in central nervous system during aging. In the present study, we have evaluated the salubrious role of grape seed extract on accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged rats. Male albino rats of Wistar strain were divided into four groups: Group I, young control rats; Group II, young rats treated with grape seed extract (100 mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results, thus, revealed that grape seed extract has inhibiting effect on the accumulation of age-related oxidative DNA damages in spinal cord and in various brain regions such as cerebral cortex, striatum and hippocampus.     

Candida tropicalis brain abscess in a neonate: An emerging nosocomial menace

Fungi are a relatively uncommon cause of brain abscess in neonates and early infancy. They are usually associated with predisposing factors like prematurity, low birth weight, use of broad-spectrum antibiotics, and prolonged stay in the intensive care unit. Candida tropicalis (C. tropicalis) is rapidly emerging as a nosocomial threat in the neonatal intensive care settings. This case report describes a neonate with C. tropicalis brain abscess who was diagnosed early and managed aggressively with a favorable outcome. Inadvertent use of intravenous antibiotics can have serious complications such as invasive fungal infection. Correct microbiological diagnosis is the key to successful treatment of deep-seated pyogenic infection. Fungal etiology should always be studied in relevant clinical settings.