Comparative Analysis of Hindgut Microbiota Variation in Protaetia brevitarsis Larvae across Diverse Farms.

Protaetia brevitarsis larvae are farm-raised for food, are used in traditional East Asian medicine, and convert organic waste into biofertilizers. Here, the comparative analysis of the gut microbiota of third-instar larvae obtained from five different farms was investigated using 16S rRNA microbial profiling. Species richness, evenness, and diversity results using α-diversity analysis (observed species, Chao1, Shannon, Simpson) were similar between farms, except for those between the TO and KO farms. ß-diversity was significantly different in distribution and relative abundance between farms (PERMANOVA, pseudo-F = 13.20, p = 0.001). At the phylum level, Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota were the most dominant, accounting for 73-88% of the hindgut microbial community. At the genus level, Tuberibacillus, Proteiniphilum, Desulfovibrio, Luoshenia, and Thermoactinomyces were the most abundant. Although oak sawdust was the main feed component, there were large variations in distribution and relative abundance across farms at the phylum and genus levels. Venn diagram and linear discriminant analysis effect size analyses revealed large variations in the hindgut microbial communities of P. brevitarsis larvae between farms. These results suggest environmental factors were more important than feed ingredients or genetic predisposition for the establishment of the intestinal microbiota of P. brevitarsis larvae. These findings serve as reference data to understand the intestinal microbiota of P. brevitarsis larvae.

Microalgae-enhanced bioremediation of Cr(VI) ions using spent coffee ground-derived magnetic biochar MoS2-Ag composites.

Composites of magnetic biochar derived from spent coffee grounds were prepared using MoS2 decorated by plasmonic silver nanoparticles (MoS2-Ag), which were used for the bioremediation Cr6+ ions. The composites were characterized by electron microscopy, X-ray diffraction, Raman, and UV-VIS spectroscopy. The bioremediation of Cr6+ ions was enhanced almost two times compared to microalgae, Spirulina maxima. Such an increased activity is attributed to heterojunction formation of Biochar@MoS2-Ag composite due to the synergetic effects of surface plasmon resonance of AgNPs inducing amplified local electric field, thus simultaneously increasing the absorption of MoS2 under visible or near-infrared light. The combination of Biochar@MoS2-Ag and Spirulina maxima powder was effective for the separation (microalga-based absorption and accumulation of Cr6+ ions) of photo-induced carriers (composite-assisted to breakdown Cr6+ ions). This study offers efficient eco-friendly treatment of Cr6+ ions by reporting the first enhanced bioremediation of Cr(VI) ions by microalgae using MoS2-Ag-modified biochar obtained from consumed coffee grounds.

Effect of a single session of yoga and meditation on stress reactivity: A systematic review.

This systematic review synthesises the evidence for the effectiveness of a single session of yoga or its components including meditation and breathing techniques in reducing acute stress reactivity in healthy adults. Following the PRISMA guidelines, we searched Medline, EMBASE, Cochrane, CINAHL, and PsycINFO on 30th July 2023 for randomised controlled or crossover trials of yoga components and reporting physiological and/or psychological outcome measure(s) related to stress reactivity. Risk of bias (ROB) was assessed using the Cochrane ROB 2 tool. Data were synthesised narratively. Twenty-one out of 28 eligible studies (n = 2574) relating to 31 interventions (meditation [n = 22], breathing [n = 4] and yoga [n = 5]) reported outcomes in favour of the intervention. Stress reactivity was reported to be reduced by 71% of studies measuring physiological outcomes and 65% of studies measuring psychological outcomes. These studies show that a single session of yoga components is effective in reducing acute stress reactivity in adults and could be recommended for stress management. Future studies with larger populations and a more equal representation of genders and age groups are warranted.

Not All Yoga Styles Are the Same: An International Survey on Characteristics of Yoga Classes.

Objectives: Yoga is a multicomponent activity that has been associated with many health benefits. Different yoga styles contain different combinations and durations of components (e.g., postures, breathing, meditation, relaxation, and chanting). A better description and quantification of yoga components within different styles are important in understanding how different yoga styles contribute to health outcomes. This survey aims to understand the general characteristics and components taught in different yoga styles. Design: An online international survey was sent to yoga teachers (18+ years with >1 year teaching experience) using snowball recruitment. Survey questions included demographic and professional characteristics of participants, specialized yoga style, and details of components typically taught in the class. The analysis included descriptive statistics and a comparison between teachers of traditional versus exercise-based versus therapy styles using χ2 and Kruskal-Wallis tests. Results: Nine hundred and sixty-eight yoga teachers (76.8% female, mean age 43.8 ± 11.1 years) from 64 countries participated in the survey. When grouped according to primary yoga style taught, 70.6% of participants taught traditional (e.g., hatha or ashtanga), 18.4% exercise-based (e.g., vinyasa or power), and 11.0% therapy (e.g., restorative or gentle) styles. Nearly all teachers included physical postures, but breath techniques, chanting, and cleansing were included by significantly more traditional teachers (95.2%, 68.3%, 25.8%, respectively) compared with exercise-based (88.6%, 42.5%, 7.2%) and therapy teachers (93.0%, 43.0%, 10.0%). Variations were reported in the time allocated to each of these class components. Physical postures took up 50.0% of total class time for traditional styles, 60.9% for exercise-based, and 53.9% for therapy styles (p < 0.001). Conversely, breath techniques, meditation, relaxation, and chanting took significantly more of the class time for traditional and therapy compared with exercise-based styles. However, teachers from all styles regarded yoga poses, breathing, meditation, and relaxation as equally important in the yoga class. Conclusions: Exercise-based yoga styles unsurprisingly dedicate more time to physical postures and less time to nonphysical components than traditional and therapy yoga styles. However, all yoga teachers report valuing and including multiple components of yoga practice regardless of the primary style of teaching, which is reflective of the holistic nature of yoga practice. Further research into the benefits of the specific component combinations in different yoga styles is needed to better understand the full potential of yoga practice for health.

Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: A randomized controlled trial.

BACKGROUND: It is uncertain whether vitamin D can reduce respiratory infection. OBJECTIVE: To determine whether vitamin D supplementation reduces influenza and other upper viral respiratory tract infections. METHODS: A total of 1300 healthy children and adolescents between the ages of 3 and 17 years were randomized to vitamin D (14 000 U weekly) or placebo for 8 months in Vietnam. The primary outcome was reverse transcriptase (RT)-PCR-confirmed influenza infection, and the coprimary outcome was multiplex PCR-confirmed non-influenza respiratory viruses. Participants, caregivers, and those assessing outcomes were blinded to group assignment. RESULTS: A total of 650 children and adolescents were randomly assigned to vitamin D and 650 to placebo. The mean baseline serum 25-hydroxyvitamin D levels were 65.7 nmol/L and 65.2 nmol/L in the intervention and placebo groups, respectively, with an increase to 91.8 nmol/L in the vitamin D group and no increase, 64.5 nmol/L, in the placebo group. All 1300 participants randomized contributed to the analysis. We observed RT-PCR-confirmed influenza A or B occurred in 50 children (7.7%) in the vitamin D group and in 43 (6.6%) in the placebo group (hazard ratio [HR]: 1.18, 95% CI: 0.79-1.78). RT-PCR-confirmed non-influenza respiratory virus infection occurred in 146 (22.5%) in the vitamin D group and in 185 (28.5%) in the placebo group (hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94). When considering all respiratory viruses, including influenza, the effect of vitamin D in reducing infection was significant, HR: 0.81, 95% CI: 0.66-0.99. CONCLUSION: Vitamin D supplementation did not reduce the incidence of influenza but moderately reduced non-influenza respiratory viral infection.

Genome and evolution of the shade-requiring medicinal herb Panax ginseng.

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA, 2017.

Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1ß, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

The distribution of phosphorus and its transformations during batch growth of Synechocystis.

Phosphorus (P) is an essential nutrient that affects the growth and metabolism of microalgal biomass. Despite the obvious importance of P, the dynamics of how it is taken up and distributed in microalgae are largely undefined. In this study, we tracked the fate of P during batch growth of the cyanobacterium Synechocystis sp. PCC 6803. We determined the distribution of P in intracellular polymeric substances (IPS), extracellular polymeric substances (EPS), and soluble microbial products (SMP) for three initial ortho-phosphate concentrations. Results show that the initial P concentration had no impact on the production of biomass, SMP, and EPS. While the initial P concentration affected the rate and the timing of how P was transformed among internal and external forms of inorganic P (IP) and organic P (OP), the trends were the same no matter the starting P concentration. Initially, IP in the bulk solution was rapidly and simultaneously adsorbed by EPS (IPEPS) and taken up as internal IP (IPint). As the bulk-solution's IP was depleted, desorption of IPEPS became the predominant source for IP that was taken up by the growing cells and converted into OPint. At the end of the 9-d batch experiments, almost all P was OP, and most of the OP was intracellular. Based on all of the results, we propose a set of transformation pathways for P during the growth of Synechocystis. Key is that EPS and intracellular P pool play important and distinct roles in the uptake and storage of P.

The complete chloroplast genome sequence of Panax vietnamensis Ha et Grushv (Araliaceae).

The complete chloroplast genome sequence of Panax vietnamensis, a medicinal herb belonging to Araliaceae family, was generated by de novo assembly using whole genome next-generation sequences. The chloroplast genome was a circular form of 155 992 bp long and showed typical chloroplast genome structure consisting of a large single-copy region of 86 177 bp, a small single copy region of 17 935 bp and a pair of inverted repeats of 25 940 bp. The chloroplast genome had 79 protein-coding genes, 29 tRNA genes and 4 rRNA genes. The phylogenetic analysis with the reported chloroplast genomes revealed that four Panax species were grouped in the same clade and P. vietnamensis is more closely related to P. notoginseng than P. ginseng and P. quinquefolius.

The Chemistry and Biological Activities of Mimosine: A Review.

Mimosine [ß-[N-(3-hydroxy-4-oxypyridyl)]-α-aminopropionic acid] is a non-protein amino acid found in the members of Mimosoideae family. There are a considerable number of reports available on the chemistry, methods for estimation, biosynthesis, regulation, and degradation of this secondary metabolite. On the other hand, over the past years of active research, mimosine has been found to have various biological activities such as anti-cancer, antiinflammation, anti-fibrosis, anti-influenza, anti-virus, herbicidal and insecticidal activities, and others. Mimosine is a leading compound of interest for use in the development of RAC/CDC42-activated kinase 1 (PAK1)-specific inhibitors for the treatment of various diseases/disorders, because PAK1 is not essential for the growth of normal cells. Interestingly, the new roles of mimosine in malignant glioma treatment, regenerative dentistry, and phytoremediation are being emerged. These identified properties indicate an exciting future for this amino acid. The present review is focused on the chemistry and recognized biological activities of mimosine in an attempt to draw a link between these two characteristics. Copyright © 2016 John Wiley & Sons, Ltd.

Artepillin C and Other Herbal PAK1-blockers: Effects on Hair Cell Proliferation and Related PAK1-dependent Biological Function in Cell Culture.

PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1-blockers such as propolis and curcumin have been shown to be anti-oncogenic and anti-melanogenic as well as anti-alopecia (promoting hair growth). Previously, we found several distinct PAK1-inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1-inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6-dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 µM as does artepillin C, the major anti-cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1-3) also exhibited a strong anti-cancer activity with the IC50 ranging from 16 to 30 µM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells.

Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives.

Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol) from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 µM, respectively). Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b) showed high insecticidal activity (LD50 = 0.5 and 0.7 µg/insect, respectively) with 50%-60% mortality at 50 µg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 µM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C5-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide.

The Supplemental Nutrition Assistance Program and dietary quality among US adults: findings from a nationally representative survey.

OBJECTIVE: To examine the association of the Supplemental Nutrition Assistance Program (SNAP) and diet quality among low-income adults. PATIENTS AND METHODS: We examined US nationally representative data from the National Health and Nutrition Examination Surveys 2003-2004, 2005-2006, 2007-2008, and 2009-2010. The data were analyzed from October 7, 2013, to March 1, 2014. The analytic sample consisted of 4211 low-income adults aged 20 to 64 years, of whom 1830 participate in SNAP. We adhered to the National Cancer Institute method in calculating the Healthy Eating Index 2010 and other dietary indicators, such as empty calorie intake. Bivariate and multivariable regression was used to compare SNAP participants and income-eligible nonparticipants among the full sample and subsamples of age, sex, race/ethnicity, and food insecurity. RESULTS: Compared with low-income nonparticipants, adjusted analyses reveal that SNAP participants had lower dietary quality scores overall (42.58 vs 44.36, P≤.0001) and lower scores for fruits and vegetables, seafood and plant proteins (1.55 vs 1.77, P≤.0022), and empty calories (9.03 vs 9.90, P≤.0001), but they exhibited comparable scores on whole grain, refined grain, total dairy, total protein, fatty acid, and sodium intakes. The association between SNAP participation and lower dietary quality was statistically significant among women, Hispanics, young adults, and individuals who were food secure. CONCLUSION: Our analyses suggest that SNAP participants have lower dietary quality than their income-eligible nonparticipant counterparts. Although SNAP has an important role in providing nutrition assistance to eligible low-income individuals, interventions are warranted to improve the dietary quality of participants.

Several herbal compounds in Okinawa plants directly inhibit the oncogenic/aging kinase PAK1.

The p21-activated kinase 1 (PAK1) is emerging as a promising therapeutic target, and the search for blockers of this oncogenic/aging kinase would be potentially useful for the treatment of various diseases/disorders in the future. Here, we report for the first time the anti-PAK1 activity of compounds derived from three distinct Okinawa plants. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) from alpinia inhibited directly PAK1 more strongly than mimosine and mimosinol from leucaena. Cucurbitacin I isolated from bitter gourd/melon also exhibited a moderate anti-PAK1 activity. Hispidin, a metabolite of DK, strongly inhibited PAK1 with the IC50 = 5.7 µM. The IC50 of three hispidin derivatives (H1-3) for PAK1 inhibition ranges from 1.2 to 2.0 µM, while mimosine tetrapeptides [mimosine-Phe-Phe-Tyr (MFFY) and mimosine-Phe-Trp-Tyr (MFWY)] inhibit PAK1 at nanomolar level (IC50 of 0.13 and 0.60 µM, respectively). Thus, we hope these derivatives of hispidin and mimosine could be used as potential leading compounds for developing far more potent anti-PAK1 drugs which would be useful for clinical application in the future.

Electrochemical impedance spectroscopy characterization of nanoporous alumina dengue virus biosensor.

The Faradaic electrochemical impedance technique is employed to characterize the impedance change of a nanoporous alumina biosensor in response towards the specific binding of dengue serotype 2 (Denv2) viral particles to its serotype 2-specific immunoglobulin G antibody within the thin alumina layer. The optimal equivalent circuit model that matches the impedimetric responses of the sensor describes three distinct regions: the electrolyte solution (R(s)), the porous alumina channels (including biomaterials) (Q(1), R(1)) and the conductive electrode substrate layer (Q(2), R(2)). Both channel resistance R(1) and capacitance Q(1) change in response to the increase of the Denv2 virus concentration. A linear relationship between R(1) and Denv2 concentration from 1 to 900 plaque forming unit per mL (pfu mL(-1)) can be derived using Langmuir-Freundlich isotherm model. At 1pfu mL(-1) Denv2 concentration, R(1) can be distinguished from that of the cell culture control sample. Moreover, Q(1) doubles when Denv2 is added but remains unchanged in the presence of two other non-specific viruses - West Nile virus and Chikungunya virus indicates biosensor specificity can be quantitatively measured using channel capacitance.

Membrane-based electrochemical nanobiosensor for the detection of virus.

A membrane-based electrochemical nanobiosensor sensitive toward whole viral particles is fabricated by forming a submicrometer thick nanoporous alumina membrane over a platinum disk electrode. Antibody probe molecules are physically adsorbed onto the walls of the membrane nanochannels. The sensing signal is based on the monitoring of the electrode's Faradaic current response toward ferrocenemethanol, which is extremely sensitive to the formation of immunocomplex within the nanoporous membrane. This nanobiosensor is demonstrated for the sensing of West Nile virus protein domain III (WNV-DIII) and the inactivated West Nile viral particle, using anti-WNV-DIII immunoglobulin M (IgM) as the biorecognition probe. The detection of the viral protein and the particle are logarithmically linear up to 53 pg mL(-1) (R(2) = 0.99) and 50 viral particles per 100 mL (R(2) = 0.93) in pH 7, with extremely low detection limits of 4 pg mL(-1) and ca. 2 viral particles per 100 mL, comparable to sensitivities of polymerase chain reaction techniques. The relative standard deviation (RSD) of whole viral particle detection in whole blood serum is 6.9%. In addition, the simple nanobiosensor construction procedure, minimal sample preparation, and short detection time of 30 min are highly attractive properties and demonstrate that the detection of a wide range of proteins and viruses can be achieved.

A phase I and pharmacokinetic study of pemetrexed plus irinotecan in patients with advanced solid malignancies.

PURPOSE: The main objectives of this phase I and pharmacokinetic, open-label study were to characterize the principal toxicities and determine the maximum tolerated dose of the multitargeted antifolate pemetrexed administered in combination with irinotecan. The study also sought to detect major pharmacokinetic drug-drug interactions between these agents and preliminary evidence of antitumor activity in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: Pemetrexed was administered as a 10-min i.v. infusion followed by irinotecan given i.v. over 90 min every 3 weeks to patients with advanced solid malignancies. The study objectives were first pursued in heavily pretreated patients and then in lightly pretreated patients who also received vitamin supplementation. RESULTS: Twenty-three heavily pretreated patients enrolled in the first stage of the study, and the maximum tolerated dose level of pemetrexed/irinotecan without vitamin supplementation was 400/250 mg/m(2); further dose escalation was precluded by severe neutropenia that was protracted and/or associated with fever. In the second stage of the study, 28 lightly pretreated patients were administered pemetrexed/irinotecan with vitamin supplementation; these patients tolerated pemetrexed/irinotecan at a dose level of 500/350 mg/m(2), which reflected clinically relevant single-agent doses of both agents. No major pharmacokinetic interactions between the agents were evident. Four patients, two patients each with colorectal cancer refractory to fluoropyrimidines and advanced mesothelioma, had partial responses. CONCLUSIONS: The pemetrexed/irinotecan regimen is well tolerated in patients with advanced solid malignancies at clinically relevant single-agent doses. The recommended dose level of pemetrexed/irinotecan for subsequent disease-directed evaluations involving lightly pretreated patients is 500/350 mg/m(2) every 3 weeks with vitamin supplementation.

Pain processing within the primary somatosensory cortex in humans.

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20- and 30-ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS-activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.