A decoupler-free simple paper microchip capillary electrophoresis device for simultaneous detection of dopamine,epinephrine and serotonin

This paper demonstrates a new and simplified configuration for capillary electrophoresis-amperometric detection (CE-AD) using a paper microfluidic chip incorporating inexpensive wax printing and screen printing based methods and then used for electrophoretic separation and simultaneous in-channel amperometric detection of three clinically relevant neurochemicals in a single run without using any decouplers. Detection of neurochemicals e.g., dopamine, epinephrine and serotonin is crucial for early prediction of neurological disorders including Parkinson''s, Alzheimer''s, dementia, as well as progressive neuro-psychiatric conditions such as depression, anxiety, as well as certain cardiovascular diseases. The plasma concentrations of such neurochemicals are as important as those present in cerebrospinal fluid (CSF) and can be useful for rapid and convenient biosensing. However, simultaneous detection of such neurochemicals in a complex mixture such as human serum requires their separation prior to detection. With the developed microchip, separation and detection of the neurochemicals were exhibited within 650 seconds without pre-treatment and the procedure was validated with spiked fetal bovine serum samples. Beside this, the developed paper microfluidic chip has potential to be integrated in point-of-care diagnosis with onsite detection ability. Moreover, the use of a straight channel capillary, a screen-printed carbon electrode without decoupler, in-channel amperometric detection and low sample volume requirements (2 μL) are shown as additional advantages.

This paper demonstrates a simplified configuration for capillary electrophoresis-amperometric detection using paper microfluidic chip for separation and simultaneous detection of three clinically relevant neurochemicals without using any decouplers.     

Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US$9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.     

Occipital sutures and its variations: the value of 3D-CT and how to differentiate it from fractures using 3D-CT?

The anatomy and embryology of occipital bone are complex and may present with a varied ossification pattern and masquerade as fractures. There are only a few articles in the literature and none on CT appearance of occiput ossification and sutures. Awareness of the normal and variant anatomy, appearance and position along with age of fusion of sutures will be helpful in confidently differentiating variant suture from fracture. This will be particularly important in children in the field of non-accidental injury with its attendant medicolegal complications. We describe the normal anatomy, embryology, normal and variant sutures of occipital bone as published in the literature so far and present a pictorial review of 15 cases of variant sutures. With CT as the primary modality in assessing for head injury now, it is important to know the CT features of these sutures, their appearance, position and variants and be able to utilize 3D-CT to be able to give a more definitive diagnosis.     

Toll‐like receptors and CD40 modulate each other's expression affecting Leishmania major infection

Toll‐like receptors (TLRs) recognize pathogen‐associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite L eishmania major. While polyinosinic‐polycytidylic acid [poly (I:C)], a TLR‐3 ligand, lipopolysaccharide (LPS), a TLR‐4 ligand, imiquimod, a TLR‐7/8 ligand and cytosine–phosphate–guanosine (CpG), a TLR‐9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR‐9 expression. Therefore, we tested the synergism between CD40 and CpG in anti‐leishmanial immune response. In L eishmania‐infected macrophages, CpG was found to reduce CD40‐induced extracellular stress‐regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)‐10, these ligands had differential effects on CD40‐induced IL‐1α, IL‐6 and IL‐12 production. CpG significantly enhanced the anti‐leishmanial function of CD40 with differential effects on IL‐4, IL‐10 and interferon (IFN)‐γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40–TLR cross‐talk that regulated the experimental L . major infection.     

Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus

Monoamines are implicated in the modulation of adult hippocampal neurogenesis in depression models and following chronic antidepressant treatment. Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-receptors Smoothened (Smo) and Patched (Ptc). Combined depletion of both serotonin and norepinephrine with para-chlorophenylalanine (PCPA) resulted in a significant decrease in Smo and Ptc mRNA within the dentate gyrus subfield of the hippocampus. However, selective depletion of serotonin, using the serotonergic neurotoxin 5,7-dihyrdroxytryptamine (5,7-DHT), or norepinephrine, using the noradrenergic neurotoxin DSP-4, did not alter expression of Shh and its co-receptors, Smo and Ptc. Acute treatment with the monoamine releasing agent, para-chloroamphetamine (PCA) significantly upregulated Smo mRNA within the dentate gyrus. However, acute or chronic treatment with pharmacological antidepressants that modulate monoaminergic neurotransmission did not regulate Shh cascade expression. These results indicate that robust changes in monoamine levels can regulate the expression of the Shh signaling cascade in the adult rodent brain.