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Transcranial Direct Current Stimulation for Treatment of ADHD: A Review of the Mechanisms of Action
No full textAttention deficit hyperactivity disorder (ADHD) is a common
neuropsychiatric disorder. The current pharmaceutical treatments are associated with side effects
and with low efficacy so that about one third of the adults do not respond to these treatments.
Transcranial direct current stimulation (tDCS) is a non-invasive and safe brain modulation technique
with promising therapeutic effects on ADHD symptoms. This paper aims to comprehensively
review the clinical trials of tDCS conducted in humans for the treatment of ADHD. We aim to review
the clinical efficacy and mechanisms of action of the technique in ADHD treatment.
Method: The databases of PubMed (1990-2017), Web of Sciences (1990-2017), Google Scholar
(1990-2017) and Scopus (1990-2017) were searched using the keywords “Attention deficit hyperactivity
disorder” OR “ADHD” AND “Transcranial direct current stimulation” OR “tDCS” AND
"treatment" AND "mechanism". The title and abstract of the papers were reviewed by at least two
authors and the relevant papers were selected for in depth review. We selected the preclinical and
clinical trials that studied the effects of tDCS on ADHD patients through measuring behavioral,
hemodynamic, or neurophysiological features.
Results: The current evidence supports the therapeutic efficacy of tDCS in the improvement of
ADHD, but, the findings are controversial. Anodal tDCS seems to be more effective than cathodal
in ADHD. In addition, the appropriate sites of stimulation are frontal cortex in particular left dorsolateral
prefrontal cortex and right inferior frontal gyrus. The tDCS can improve inhibitory control
and interference control in ADHD patients.
Conclusion: tDCS has shown promising but limited clinical efficacy for ADHD treatment. However,
the current evidence supports continuing the preclinical and clinical studies to determine
physiological mechanisms and dose response of tDCS in ADHD to establish a clinical protocol
PV1, a novel Plasmodium falciparum merozoite dense granule protein, interacts with exported protein in infected erythrocytes
No full textUpon invasion, Plasmodium falciparum exports hundreds of proteins across its surrounding parasitophorous vacuole membrane (PVM) to remodel the infected erythrocyte. Although this phenomenon is crucial for the parasite growth and virulence, elucidation of precise steps in the export pathway is still required. A translocon protein complex, PTEX, is the only known pathway that mediates passage of exported proteins across the PVM. P. falciparum Parasitophorous Vacuolar protein 1 (PfPV1), a previously reported parasitophorous vacuole (PV) protein, is considered essential for parasite growth. In this study, we characterized PfPV1 as a novel merozoite dense granule protein. Structured illumination microscopy (SIM) analyses demonstrated that PfPV1 partially co-localized with EXP2, suggesting the protein could be a PTEX accessory molecule. Furthermore, PfPV1 and exported protein PTP5 co-immunoprecipitated with anti-PfPV1 antibody. Surface plasmon resonance (SPR) confirmed the proteins’ direct interaction. Additionally, we identified a PfPV1 High-affinity Region (PHR) at the C-terminal side of PTP5 where PfPV1 dominantly bound. SIM analysis demonstrated an export arrest of PTP5ΔPHR, a PTP5 mutant lacking PHR, suggesting PHR is essential for PTP5 export to the infected erythrocyte cytosol. The overall results suggest that PfPV1, a novel dense granule protein, plays an important role in protein export at PV
Identification of target proteins of clinical immunity to Plasmodium falciparum in a region of low malaria transmission
No full textThe target molecules of antibodies against falciparum malaria remain largely unknown. Recently we have identified multiple proteins as targets of immunity against Plasmodium falciparum using African serum samples. To investigate whether potential targets of clinical immunity differ with transmission intensity, we assessed immune responses in residents of low malaria transmission region in Thailand. Malaria asymptomatic volunteers (Asy: n = 19) and symptomatic patients (Sym: n = 21) were enrolled into the study. Serum immunoreactivity to 186 wheat germ cell-free system (WGCFS)-synthesized recombinant P. falciparum asexual-blood stage proteins were determined by AlphaScreen, and subsequently compared between the study groups. Forty proteins were determined as immunoreactive with antibody responses to 35 proteins being higher in Asy group than in Sym group. Among the 35 proteins, antibodies to MSP3, MSPDBL1, RH2b, and MSP7 were significantly higher in Asy than Sym (unadjusted p < 0.005) suggesting these antigens may have a protective role in clinical malaria. MSP3 reactivity remained significantly different between Asy and Sym groups even after multiple comparison adjustments (adjusted p = 0.033). Interestingly, while our two preceding studies using African sera were conducted differently (e.g., cross-sectional vs. longitudinal design, observed clinical manifestation vs. functional activity), those studies similarly identified MSP3 and MSPDBL1 as potential targets of protective immunity. This study further provides a strong rationale for the application of WGCFS-based immunoprofiling to malaria vaccine candidate and biomarker discovery even in low or reduced malaria transmission settings
Turnitin Guide on creating a profile adding class, assigment and submission
No full textMount Kenya University (MKU), recognizes and encourages the individual effort and originalities on the part of its schools, employees, students and collaborators leading to the creation of scholarly work. Academic integrity, is the foundation of university success, and encompasses honest and responsible scholarship. Plagiarism is a prime intellectual offense in that the borrower is faking the learning process. This guide aims to guide users on how to register in turnitin, create class and assignment and finally on how to add student to a class. It also covers on how to submit work to turnitin and interpret the originality report
Evaluation of Cyanide Levels in Two Cassava Varieties (Mariwa and Nyakatanegi) Grown in Bar-agulu, Siaya County, Kenya.
No full textMannihot esculenta Crantz (Cassava) is the second highest producer of carbohydrates after sugarcane. However, some varieties have high levels of cyanogenic glycosides and therefore are potentially toxic for human consumption. Nyakatanegi is one of the local varieties cultivated in Bar-agulu village in Siaya County (Kenya) and has been severally in the recent past reported to cause fatal cyanide toxicity. The other variety which is rarely associated with cassava poisoning is Mariwa. The objective of the current study was to determine cyanide levels in the two cassava varieties (Mariwa and Nyakatanegi) which are locally cultivated in Siaya County. The study was based on three laboratory assays: the picrate paper, picrate in solution and titration. Whole root cassava tubers were collected from a farmer in Bar-agulu village, Siaya County, packaged separately and transported to Mount Kenya University Pharmaceutical Chemistry Laboratory for analysis. Voucher specimens were authenticated in the cassava laboratories at Jomo Kenyatta University of Agriculture and Technology. It was observed that all the cortex samples of Nyakatanegi variety had the highest concentrations of cyanide giving 400 ppm for the picrate paper assay, 14.10 mg/Kg for the picrate in solution and 63 mg/Kg for the titration assays. On the other hand, the cortex samples of Mariwa reported cyanide concentrations of 30 ppm, 11.20 mg/Kg and 27.20 mg/Kg for the picrate paper, picrate in solution and titration assays respectively. The results showed higher amounts of cyanide in the tested cassava varieties than the WHO recommended levels (10 mg/Kg) especially the Nyakatanegi variety. Based on these results, sensitization campaigns are necessary to minimize cases of cyanide poisoning following cassava consumption
Computer-Supported Collaborative Learning and Assessment: A Strategy for Developing Online Learning Communities in Continuing Education
No full textThis chapter focuses on re-interpreting the findings of a recent study based on collaborative learning perspectives. The study utilized a case study design in which two online postgraduate courses were investigated as a collective case study. Online observations, analysis of the archived course content and interview transcripts were used as data collection techniques. The data from multiple sources were triangulated. Qualitative techniques were used in data analysis and descriptive statistics were integrated to extend the meaning of qualitative data. The findings of the study suggest that social interactivity is pivotal to facilitating meaningful learning in formal online education. The findings further illustrate that development of productive communities in continuing (in-service) education is a gradual process that evolves through four stages starting from community of interest to community of practice
Chapter Six - Controlling the Lability of Square-Planar Pt(II) Complexes Through Electronic and π-Conjugation: Correlation Between Kinetics and Theoretical Parameters
No full textIn this chapter, we report on some of the highlights of the research work which has been carried out in our laboratories on the role and influence of nitrogen-/carbon-donor tridentate ligands (NˆC/NˆN/C) on the rate of substitution of labile ligands from model square-planar Pt(II) complexes. This work was founded on the hypothesis that tailored kinetic control of substitution reactions through changing the electronic properties of the spectator ligand backbone of Pt(II) complexes can be an insightful avenue toward the optimization of the efficacy of future antitumor Pt(II) drugs. Focusing on the nitrogen-/carbon-donor tridentates (NˆC/NˆN/C), several Pt(II) complexes were synthesized and used to study systematically the mechanisms and rates of substituting the labile coligand from the complexes using biorelevant nucleophiles. The trends in reactivity as the nonleaving ligands in the complexes were systematically changed were used to understand the electronic and steric roles of the coordinated tridentate/bidentates on the lability of their complexes. Our kinetic data source can be used for the tailor-designing of future metal-based drugs with rigid nonleaving ligands, given that the lability of such complexes in biological systems plays a role on their ultimate in vivo pharmacokinetics (i.e., toxicity, deactivation and development of resistance, and cytotoxicity)
In vitro antibacterial activities, safety studies and phytochemical screening of Dregea Schimperi clark (Asclepiadaceae) extracts
No full textPlants synthesize phytochemical compounds for protection against
environmental stress and diseases. Some of the phytochemicals are
used for curative and preventive medicine. Over 90% plant materials
are used in traditional medicine to treat diseases in human and
veterinary diseases. Since a great percentage of plant materials used
lack sufficient scientific data to back their healing claims, the current
study focused on the evaluation of antimicrobial, cytotoxic and
phytochemical properties of methanolic and water extracts of Dregea
schimpheri leaves and husks. D. schimperi has many ethnomedical
claims including the management of infectious diseases. Disc diffusion
method was used to assay for antimicrobial activities of the methanolic
and water extracts of leaves and husks against Staphylococcus aureus,
Micrococcus luteus, Bacillus pumilus, Pseudomonas aerugnosa and
Escherichia coli. Cytotoxicity of the extracts was determined by use of brine shrimp lethality
test. Qualitative phytochemical screening of the husks and leaves was performed with
standard phytochemical tests. Antibacterial results were tabulated as mean zone of inhibition
± SEM. LC50 values for brine shrimp lethality test were estimated using Graphed Prism
Version 5 statistical software. Phytochemical screening observations were also tabulated.
Most extracts exhibited antibacterial activity against S. aureus, M. luteus, B. pumilus, E. coli
and P. aurignosa. Water and methanol husk extracts of D. schimperi were found to be
cytotoxic (LC50 ˂100µg/ml) while all leaf extracts had moderate to low toxicity.
Phytochemical screening revealed presence of alkaloids, phenols, tannins in both leaf and
husk powders. Saponins and anthraquinones were present in leaf extracts but absent in the
husks. The antibacterial and cytotoxic activities are attributed to the presence of these
secondary metabolites. Further studies aimed at isolating the bioactive compounds with
antibacterial and cytotoxic properties are recommended. In vitro and in vivo toxicity studies
are also necessary