Role of ABCB1 C3435T variant in response to antiepileptic drugs in epilepsy: a review

Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area

Determinants of Japanese direct investments in selected BIMP-EAGA countries

This paper uses panel data analysis to identify how Japanese multinational corporations (MNCs) allocate their investments in the selected BIMP-EAGA countries (i.e. Malaysia, Indonesia and the Philippines). The paper hypothesizes that the following six elements would influence the inflow of Japanese Direct Investments (JDI) into the area: country?s market size, growth rate of market size, per capita income, trade deficit, inflation rates and political condition. The main findings from the panel data analysis are that there is a significant relationship between Japanese direct investments and political condition in the recipient countries. The inflows of Japanese investment tend to decrease as the political risk increases. It means that Japanese MNCs tend to allocate more investments into the countries with better political condition

Verilog Modeling of Transmission Line for USB 2.0 High-Speed PHY Interface

A Verilog model is proposed for transmission lines to perform the all-Verilog simulation of high-speed chip-to-chip interface system, which reduces the simulation time by around 770 times compared to the mixed-mode simulation. The single-pulse response of transmission line in SPICE model is converted into that in Verilog model by converting the full-scale analog signal into an 11-bit digital code after uniform time sampling. The receiver waveform of transmission line is calculated by adding or subtracting the single-pulse response in Verilog model depending on the transmitting digital code values with appropriate time delay. The application of this work to a USB 2.0 high-speed PHY interface reduces the simulation time to less than three minutes with error less than 5% while the mixed-mode simulation takes more than two days for the same circuit.X1133Ysciescopu

Effects of fermentation time and pH on soursop (Annona muricata) vinegar production towards its chemical compositions

Vinegar is a liquid product that undergoes both alcoholic and acetous fermentation of sugar (carbohydrate) sources. Soursop (Annona muricata) is easily available in Malaysia throughout the year. However, it is also highly perishable and has a short shelf-life. Therefore, in this research, soursop was used in the production of vinegar, to increase its utilisation and reduce wastage. The objectives of this research were to determine the effects of fermentation time and pH on soursop vinegar using a 3 × 5 factorial design and to determine its chemical compositions. It was found that pH and fermentation time showed significant (p0.05). It was evident that the sugar concentration reduces over time and it was inversely proportional to the ethanol and acetic acid concentrations, due to the conversion of sugar to ethanol and subsequently acetic acid. It was found that higher pH (pH5.5) gave significantly (p0.05) effect on ethanol production. There were no significant differences (p>0.05) in vitamin C content in all vinegar samples. Thus, it can be established that at fermentation time of 120 h and pH5.5, more sugar was used and more ethanol and acetic acid were produced

Inspiratory muscle training (IMT) for adults discharged from hospital with community acquired pneumonia (CAP) – a feasibility study

Patients report significant morbidity following community-acquired pneumonia (CAP); 70% report persistent symptoms and up to 50% impaired daily activity at 4 weeks post-discharge. Respiratory muscle weakness is one possible mechanism for delayed recovery. Inspiratory muscle training (IMT) increases strength and endurance of inspiratory muscles, with improvements in patient-reported outcomes in other conditions. To our knowledge IMT has not previously been investigated in CAP. To assess the tolerability of IMT in adults discharged from hospital with community-acquired pneumonia. Patients hospitalised with a diagnosis of CAP between February 2017 and March 2018 were eligible for inclusion and convenience sampling was used for participant selection. Participants received an IMT device (POWERbreath KHP2) following familiarisation. Training frequency (twice daily) and load (50% PImax) were fixed, however training volume was incremental during weeks 1–3 (10, 20, 30 breaths) and constant thereafter (30 breaths.) Participants were followed by combination of telephone and clinic visits for 9 weeks. Outcomes of interest were; utilisation of IMT device per protocol (defined as >94% training adherence), patient-reported IMT acceptability, and number of device-related side effects. Statistical analysis was conducted using Stata (version 15.1.) Twenty-two participants were recruited; 16 were male (72.7%), mean age was 55.2 years (range 27.9–77.3.) Participants completed IMT per protocol in 72.7% cases. One unrelated, unexpected serious adverse event (death) occurred during follow-up and 3 participants active at this time were stopped from further IMT by research sponsor pending investigation. Two participants were lost to follow-up. Side effects during IMT were reported on 15 occasions across 22 participants over a total 1183 training days. Reported side effects included chest pain (x2), cough (x1), dyspnoea (x4), and dizziness (x8). All side-effects were rated grade 1 and did not prevent participants from continuing training. Participant-reported IMT acceptability, defined by participants rating training as both ‘useful’ and ‘helpful’ at each follow-up contact, was 99.4%. Inspiratory muscle training appears to be safe, tolerable, and acceptable to patients following CAP. Distinguishing CAP related symptoms and device-related side effects is challenging in patients recovering following an acute infective illness. A clinical trial to determine efficacy is warranted.Nottingham University Hospitals Trus

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

Laser Cooling of Optically Trapped Molecules

Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap (ODT) and subsequently laser cooled within the trap. Starting with magneto-optical trapping, we sub-Doppler cool CaF and then load $150(30)$ CaF molecules into an ODT. Enhanced loading by a factor of five is obtained when sub-Doppler cooling light and trapping light are on simultaneously. For trapped molecules, we directly observe efficient sub-Doppler cooling to a temperature of $60(5)$ $\mu\text{K}$. The trapped molecular density of $8(2)\times10^7$ cm$^{-3}$ is an order of magnitude greater than in the initial sub-Doppler cooled sample. The trap lifetime of 750(40) ms is dominated by background gas collisions.Comment: 5 pages, 5 figure

Molecular cloning and transcriptional activity of a new Petunia calreticulin gene involved in pistil transmitting tract maturation, progamic phase, and double fertilization

Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca2+-binding protein in multicellular eukaryotes. As an endoplasmic reticulum-resident protein, CRT plays a key role in many cellular processes including Ca2+ storage and release, protein synthesis, and molecular chaperoning in both animals and plants. CRT has long been suggested to play a role in plant sexual reproduction. To begin to address this possibility, we cloned and characterized the full-length cDNA of a new CRT gene (PhCRT) from Petunia. The deduced amino acid sequence of PhCRT shares homology with other known plant CRTs, and phylogenetic analysis indicates that the PhCRT cDNA clone belongs to the CRT1/CRT2 subclass. Northern blot analysis and fluorescent in situ hybridization were used to assess PhCRT gene expression in different parts of the pistil before pollination, during subsequent stages of the progamic phase, and at fertilization. The highest level of PhCRT mRNA was detected in the stigma–style part of the unpollinated pistil 1 day before anthesis and during the early stage of the progamic phase, when pollen is germinated and tubes outgrow on the stigma. In the ovary, PhCRT mRNA was most abundant after pollination and reached maximum at the late stage of the progamic phase, when pollen tubes grow into the ovules and fertilization occurs. PhCRT mRNA transcripts were seen to accumulate predominantly in transmitting tract cells of maturing and receptive stigma, in germinated pollen/growing tubes, and at the micropylar region of the ovule, where the female gametophyte is located. From these results, we suggest that PhCRT gene expression is up-regulated during secretory activity of the pistil transmitting tract cells, pollen germination and outgrowth of the tubes, and then during gamete fusion and early embryogenesis

Influence of the initial chemical conditions on the rational design of silica particles

The influence of the water content in the initial composition on the size of silica particles produced using the Stöber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical Stöber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site