Focal seizures unfold variably over time.

This scientific commentary refers to 'Chronic intracranial EEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states' by Schroeder et al. (https://doi.org/10.1093/braincomms/fcad205)

Effect of neurostimulation on cognition and mood in refractory epilepsy.

Epilepsy is a common, debilitating neurological disorder characterized by recurrent seizures. Mood disorders and cognitive deficits are common comorbidities in epilepsy that, like seizures, profoundly influence quality of life and can be difficult to treat. For patients with refractory epilepsy who are not candidates for resection, neurostimulation, the electrical modulation of epileptogenic brain tissue, is an emerging treatment alternative. Several forms of neurostimulation are currently available, and therapy selection hinges on relative efficacy for seizure control and amelioration of neuropsychiatric comorbidities. Here, we review the current evidence for how invasive and noninvasive neurostimulation therapies affect mood and cognition in persons with epilepsy. Invasive therapies include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Noninvasive therapies include trigeminal nerve stimulation (TNS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, current evidence supports stable cognition and mood with all neurostimulation therapies, although there is some evidence that cognition and mood may improve with invasive forms of neurostimulation. More research is required to optimize the effects of neurostimulation for improvements in cognition and mood

Prevention and partial reversion of the lupus phenotype in ABIN1[D485N] mice by an IRAK4 inhibitor

OBJECTIVE: We have reported previously that the IRAK4 inhibitor PF06426779 given to ubiquitin-binding-defective ABIN1[D485N] mice at 6 weeks of age prevents the major facets of lupus that develop 10 weeks later. The present study was undertaken to investigate whether PF06426779 could reverse the lupus phenotype when administered to 13-week-old ABIN1[D485N] mice that had already developed symptoms of lupus. METHODS: Splenomegaly, the number of splenic neutrophils, T(FH) and Germinal Centre B (GCB) cells, serum levels of immunoglobulins, the extent of kidney, liver and lung pathology, and glomerular IgA and IgM were measured after feeding 13-week-old ABIN1[D485N] and wild-type mice for another 10 weeks with R&M3 diet with and without PF06426779 (4 g/kg). RESULTS: Following drug treatment, spleen size and weight, splenic neutrophil numbers, and serum IgA and glomerular IgA levels of ABIN1[D485N] mice returned to those seen in wild-type mice. The rise in splenic T(FH) and GCB numbers, the increase in kidney and liver pathology, and the concentrations of serum IgG1, IgG2A and IgE between 13 and 23 weeks were suppressed. There was no reduction in the level of anti-self double-stranded DNA, anti-self nuclear antigens or IgM during the drug treatment. CONCLUSIONS: The results demonstrate the therapeutic potential of IRAK4 inhibitors for the treatment of lupus and raise the possibility of monitoring efficacy by measuring decreases in the serum levels of IgA. Our results support the view that there may be a closer connection between lupus and IgA nephropathy than realised previously

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling

Toll-like receptors (TLRs) form part of the host innate immune system, in which they act as sensors of microbial and endogenous danger signals. Upon TLR activation, the intracellular Toll/interleukin-1 receptor domains of TLR dimers initiate oligomerization of a multiprotein signaling platform comprising myeloid differentiation primary response 88 (MyD88) and members of the interleukin-1 receptor-associated kinase (IRAK) family. Formation of this myddosome complex initiates signal transduction pathways, leading to the activation of transcription factors and the production of inflammatory cytokines. To date, little is known about the assembly and disassembly of the myddosome and about the mechanisms by which these complexes mediate multiple downstream signaling pathways. Here, we isolated myddosome complexes from whole-cell lysates of TLR-activated primary mouse macrophages and from IRAK reporter macrophages to examine the kinetics of myddosome assembly and disassembly. Using a selective inhibitor of IRAK4\u27s kinase activity, we found that whereas TLR cytokine responses were ablated, myddosome formation was stabilized in the absence of IRAK4\u27s kinase activity. Of note, IRAK4 inhibition had only a minimal effect on NF-kappaB and mitogen-activated protein kinase (MAPK) signaling. In summary, our results indicate that IRAK4 has a critical scaffold function in myddosome formation and that its kinase activity is dispensable for myddosome assembly and activation of the NF-kappaB and MAPK pathways but is essential for MyD88-dependent production of inflammatory cytokines. Our findings suggest that the scaffold function of IRAK4 may be an attractive target for treating inflammatory and autoimmune diseases

An Analytical Study on Pippalyasava

Pippalyasava is one of the important and common preparation used by practitioners for various ailments. Lot of references are available regarding Pippalyasava in classics and are abundant in market. As a part of study Pippalyasava is prepared and observed for 6 months also these samples were subjected to following analytical parameters like organoleptic characters, physical characters, chemical characters and TLC during 2nd month and 6th month to ensure the quality of the prepared sample

A Review on the concept of Anupana in Ayurveda

Ayurveda which is the science of life is famous all over the world because of its unique concepts and practising methods. The main aim of Ayurveda is to attain Dhatusamyakriya, and through that maintain the Swasthyata of the body. Anupana is one of the unique concept of Ayurveda which plays an important role in the treatment. Anupana is that material which is consumed along with food or medicine. It can increase the palatability of the food or medicine, can improve the digestion and absorption and also act as a vehicle which carries the drug to their target site. Hence this article deals with the importance of Anupana in the Ayurvedic practise

Development and characterization of ternary solid dispersion systems of olmesartan medoxomil

The ternary solid dispersion systems of poorly water soluble olmesartan medoxomil (OLM) were prepared by conventional kneading method in order to improve its physicochemical performance. A 32 full factorial design approach was employed to optimize influence of concentration of polyvinylpyrrolidone K30 (PVP) and poloxamer 407 (PLX) on physicochemical characteristics of these dispersions. All formulations were characterized by XRPD, DSC and dissolution studies. Physical studies revealed complete loss of crystallinity and formation of uniform molecular dispersion of OLM in its ternary systems. All dispersion systems showed significant improvement in dissolution profile in comparison to pure drug alone (p 2 : 68.43 ± 2.8 %) of OLM suggesting optimum ratio of carrier system. The kinetic study of dissolution displayed to follow the Korsmeyer-Peppas model (r2 = 0.9835).Colegio de Farmacéuticos de la Provincia de Buenos Aire