Investigation of the Optimal Parameters of Median Nerve Stimulation Using a Variety of Stimulation Methods and Its Effects on Heart Rate Variability: A Systematic Review.

OBJECTIVES: There is a wealth of literature supporting the use of median nerve stimulation (MNS) for modulating autonomic nervous system (ANS) dysfunction such as in hypoxia, recovery after heart valve replacement, ischemia, and cardiac contractibility. Heart rate variability (HRV) is considered a gold standard for measuring autonomic modulation and dynamic nonlinear ANS processes through the use of an electrocardiogram (ECG). Although the use of MNS on HRV in animals and humans has been documented, optimal stimulation parameters are yet to be outlined. MATERIALS AND METHODS: This review aims to synthesize findings of neurostimulation using MNS on animals and humans while observing HRV using an ECG. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with search parameters of "Median nerve stimulation," "Neiguan," "PC-6," "HRV," "Heart rate variability," and "Heart-rate variability" observing on animals and human subjects, we found a total of 17 eligible articles. RESULTS: In this review, changing two parameters, that is, stimulation frequency and side of stimulation, appears to be the most influential in effecting frequency-domain ECG analysis of HRV. However, it is evident from this review that to perform an effective comparison of the effects of MNS on HRV, more detailed reports of the studies are required. CONCLUSIONS: Finding the optimal stimulation parameters for MNS is crucial for improving HRV. This will in turn contribute to normalizing ANS function impaired in numerous clinical conditions, such as epilepsy or diabetes.

Ex Vivo Maturation Assay for Testing Antimalarial Sensitivity of Rodent Malaria Parasites.

Ex vivo assay systems provide a powerful approach to studying human malaria parasite biology and to testing antimalarials. For rodent malaria parasites, short-term in vitro culture and ex vivo antimalarial susceptibility assays are relatively cumbersome, relying on in vivo passage for synchronization, since ring-stage parasites are an essential starting material. Here, we describe a new approach based on the enrichment of ring-stage Plasmodium berghei, P. yoelii, and P. vinckei vinckei using a single-step Percoll gradient. Importantly, we demonstrate that the enriched ring-stage parasites develop synchronously regardless of the parasite strain or species used. Using a flow cytometry assay with Hoechst and ethidium or MitoTracker dye, we show that parasite development is easily and rapidly monitored. Finally, we demonstrate that this approach can be used to screen antimalarial drugs.

Comparative quantification of dietary supplemented neural creatine concentrations with (1)H-MRS peak fitting and basis spectrum methods.

Magnetic resonance spectroscopy (MRS) is an analytical procedure that can be used to non-invasively measure the concentration of a range of neural metabolites. Creatine is an important neurometabolite with dietary supplementation offering therapeutic potential for neurological disorders with dysfunctional energetic processes. Neural creatine concentrations can be probed using proton MRS and quantified using a range of software packages based on different analytical methods. This experiment examines the differences in quantification performance of two commonly used analysis packages following a creatine supplementation strategy with potential therapeutic application. Human participants followed a seven day dietary supplementation regime in a placebo-controlled, cross-over design interspersed with a five week wash-out period. Spectroscopy data were acquired the day immediately following supplementation and analyzed with two commonly-used software packages which employ vastly different quantification methods. Results demonstrate that neural creatine concentration was augmented following creatine supplementation when analyzed using the peak fitting method of quantification (105.9%±10.1). In contrast, no change in neural creatine levels were detected with supplementation when analysis was conducted using the basis spectrum method of quantification (102.6%±8.6). Results suggest that software packages that employ the peak fitting procedure for spectral quantification are possibly more sensitive to subtle changes in neural creatine concentrations. The relative simplicity of the spectroscopy sequence and the data analysis procedure suggest that peak fitting procedures may be the most effective means of metabolite quantification when detection of subtle alterations in neural metabolites is necessary. The straightforward technique can be used on a clinical magnetic resonance imaging system.

A whole cell pathway screen reveals seven novel chemosensitizers to combat chloroquine resistant malaria.

Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in the 1990s despite its initial promise of disease eradication. Since then, resistance-conferring mutations have been identified in transporters such as the PfCRT, that allow for the efflux of CQ from its primary site of action, the parasite digestive vacuole. Chemosensitizing/chemoreversing compounds interfere with the function of these transporters thereby sensitizing parasites to CQ once again. However, compounds identified thus far have disappointing in vivo efficacy and screening for alternative candidates is required to revive this strategy. In this study, we propose a simple and direct means to rapidly screen for such compounds using a fluorescent-tagged CQ molecule. When this screen was applied to a small library, seven novel chemosensitizers (octoclothepin, methiothepin, metergoline, loperamide, chlorprothixene, L-703,606 and mibefradil) were quickly elucidated, including two which showed greater potency than the classical chemosensitizers verapamil and desipramine.

A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development.

Microscopic examination of Giemsa-stained thin blood smears remains the gold standard method used to quantify and stage malaria parasites. However, this technique is tedious, and requires trained microscopists. We have developed a fast and simple flow cytometry method to quantify and stage, various malaria parasites in red blood cells in whole blood or in vitro cultured Plasmodium falciparum. The parasites were stained with dihydroethidium and Hoechst 33342 or SYBR Green I and leukocytes were identified with an antibody against CD45. Depending on the DNA stains used, samples were analyzed using different models of flow cytometers. This protocol, which does not require any washing steps, allows infected red blood cells to be distinguished from leukocytes, as well as allowing non-infected reticulocytes and normocytes to be identified. It also allows assessing the proportion of parasites at different developmental stages. Lastly, we demonstrate how this technique can be applied to antimalarial drug testing.

Combined 633-nm and 830-nm led treatment of photoaging skin.

OBJECTIVES: To evaluate the clinical efficacy and ultrastructural changes in photodamaged skin after combined 633-nm and 830-nm light-emitting diode (LED) treatments. METHODS: Thirty-six subjects received 9 LED treatments over the course of 5 weeks and were subsequently evaluated for final clinical improvement 12 weeks after treatment. Five subjects were also biopsied to determine the ultrastuctural posttreatment changes in collagen fibers. RESULTS: A statistically significant improvement in wrinkles was seen after profilometric analysis. The majority of subjects reported improvements in softness, smoothness, and firmness at all time points. Electron microscopic analysis showed evidence of post-LED treatment of thicker collagen fibers. CONCLUSIONS: 633-nm and 830-nm LED treatments play a role in the treatment of photodamaged skin. LED treatments can be used as either a primary or adjunctive treatment modality.

Combination blue (415 nm) and red (633 nm) LED phototherapy in the treatment of mild to severe acne vulgaris.

BACKGROUND AND OBJECTIVE: Acne vulgaris represents both a challenge to the treating dermatologist and a major concern for the patient. Conventional treatments have proved inconsistent with often unacceptable side effects and high rates of recurrence. Non-thermal, non-laser, phototherapy for acne with a combination of blue and red light has recently attracted attention. The present study was designed to assess the efficacy of this combination phototherapy. METHODS: Twenty-four subjects, Fitzpatrick skin types II-V, with mild to severe symmetric facial acne vulgaris were recruited for the study. Subjects were well matched at baseline in terms of both age and duration of acne. Subjects were treated over eight sessions, two per week 3 days apart, alternating between 415 nm blue light (20 minutes/session, 48 J/cm2) and 633 nm red light (20 minutes/session, 96 J/cm2) from a light-emitting diode (LED)-based therapy system. Patients received a mild microdermabrasion before each session. Acne was assessed at baseline and at weeks 2, 4, 8 and 12. RESULTS: Twenty-two patients completed the trial. A mean reduction in lesion count was observed at all follow-up points. At the 4-week follow-up, the mean lesion count reduction was significant at 46% (p=0.001). At the 12-week follow-up, the mean lesion count reduction was also significant at 81% (p=0.001). Patient and dermatologist assessments were similar. Severe acne showed a marginally better response than mild acne. Side effects were minimal and transitory. Comedones did not respond as well as inflammatory lesions. CONCLUSIONS: Combination blue and red LED therapy appears to have excellent potential in the treatment of mild to severe acne. Treatment appears to be both pain- and side effect-free.