Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

PURPOSE: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. METHODS: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. RESULTS: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). CONCLUSION: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.

Force Control Strategy of Five-Digit Precision Grasping With Aligned and Unaligned Configurations.

OBJECTIVE: To investigate the digit force control during a five-digit precision grasp in aligned (AG) and unaligned grasping (UG) configurations. BACKGROUND: The effects of various cylindrical handles for tools on power grasp performance have been previously investigated. However, there is little information on force control strategy of precision grasp to fit various grasping configurations. METHOD: Twenty healthy young adults were recruited to perform a lift-hold-lower task. The AG and UG configurations on a cylindrical simulator with force transducers were adjusted for each individual. The applied force and moment, the force variability during holding, and force correlations between thumb and each finger were measured. RESULT: No differences in applied force, force correlation, repeatability, and variability were found between configurations. However, the moments applied in UG were significantly larger than those in AG. CONCLUSION: The force control during precision grasp did not change significantly across AG and UG except for the digit moment. The simulator is controlled efficiently with large moment during UG, which is thus the optimal configuration for precision grasping with a cylindrical handle. Further research should consider the effects of task type and handle design on force control, especially for individuals with hand disorders. APPLICATION: To design the handle of specific tool, one should consider the appropriate configuration according to the task requirements of precision grasping to reduce the risk of accumulating extra loads on digits with a cylindrical handle.

Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo.

An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested. These GSK-3i's reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy (ART) in the absence of T cell activation, release of inflammatory cytokines, cell toxicity, or impaired effector function of cytotoxic T lymphocytes or NK cells. However, when administered in vivo to SIV-infected rhesus macaques on suppressive ART, tideglusib exhibited poor pharmacodynamic properties and resulted in no clear evidence of significant SIV latency reversal. Whether alternative pharmacological formulations or combinations of this drug with other classes of LRAs will lead to an effective in vivo latency-reversing strategy remains to be determined.IMPORTANCE If combined with immune therapeutics, latency reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8+ T and NK cell cytotoxic effector functions. This new class of LRAs corresponds to inhibitors of glycogen synthase kinase-3. In this work, we have also studied the effects of one member of this drug class, tideglusib, in SIV-infected rhesus monkeys. When tested in vivo, however, tideglusib showed unfavorable pharmacokinetic properties, which resulted in lack of SIV latency reversal. The disconnect between our ex vivo and in vivo results highlights the importance of developing next generation LRAs with pharmacological properties that allow systemic drug delivery in relevant anatomical compartments harboring latent reservoirs.

Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection.

The primary reservoir for HIV is within memory CD4+ T cells residing within tissues, yet the features that make some of these cells more susceptible than others to infection by HIV is not well understood. Recent studies demonstrated that CCR5-tropic HIV-1 efficiently enters tissue-derived memory CD4+ T cells expressing CD127, the alpha chain of the IL7 receptor, but rarely completes the replication cycle. We now demonstrate that the inability of HIV to replicate in these CD127-expressing cells is not due to post-entry restriction by SAMHD1. Rather, relative to other memory T cell subsets, these cells are highly prone to undergoing latent infection with HIV, as revealed by the high levels of integrated HIV DNA in these cells. Host gene expression profiling revealed that CD127-expressing memory CD4+ T cells are phenotypically distinct from other tissue memory CD4+ T cells, and are defined by a quiescent state with diminished NFκB, NFAT, and Ox40 signaling. However, latently-infected CD127+ cells harbored unspliced HIV transcripts and stimulation of these cells with anti-CD3/CD28 reversed latency. These findings identify a novel subset of memory CD4+ T cells found in tissue and not in blood that are preferentially targeted for latent infection by HIV, and may serve as an important reservoir to target for HIV eradication efforts.

Efficacy and airway complications of Parker Flex-Tip tubes and standard endotracheal tubes during airway manipulation: A meta-analysis and trial sequential analysis.

BACKGROUND: Despite reported superior intubation outcomes associated with Parker Flex-Tip (PFT) tubes compared with those associated with standard polyvinylchloride tubes, the efficacy and safety of PFT tubes remain uncertain. OBJECTIVES: To compare the intubation outcomes between PFT and conventional standard polyvinylchloride tubes. DESIGN: Meta-analysis of randomised controlled trials. DATA SOURCES: Embase, Medline, Google Scholar, PubMed and the Cochrane controlled trials register from inception until 3 January 2021. ELIGIBILITY CRITERIA: All randomised trials comparing intubation outcomes between PFT (PFT group) and standard polyvinylchloride (standard polyvinylchloride group) tubes. RESULTS: Analysis of the 13 eligible trials showed no significant difference in successful first-attempt intubation rate [risk ratio (RR) 1.20, 95% confidence interval (CI) 0.99 to 1.44] (6 trials, 568 participants), trauma risk (RR 0.83, 95% CI 0.67 to 1.03) (5 trials, 501 participants) as well as the overall risks of epistaxis (RR 0.58, 95% CI 0.26 to 1.31) (3 trials, 262 participants), sore throat (RR 0.90, 95% CI 0.70 to 1.17) (4 trials, 451 participants) and hoarseness (RR 0.71, 95% CI 0.44 to 1.14) (4 trials, 451 participants) between the two groups. However, the intubation time was slightly shorter (weighted mean difference -4.2 s, 95% CI -7.4 to -1.0 s) (8 trials, 759 participants) and the risks of severe epistaxis (RR 0.15, 95% CI 0.03 to 0.84) (3 trials, 262 participants) and overall difficulty in airway manipulation (RR 0.48, 95% CI 0.29 to 0.80) (8 trials, 647 participants) were lower in the PFT group than those in the standard polyvinylchloride group. Trial sequential analysis conclusively confirmed a shorter intubation time with PFT tubes than with standard polyvinylchloride tubes, whereas other intubation outcomes were inconclusive. CONCLUSION: The use of PFT tubes for airway manipulation was associated with a shorter intubation time compared with the standard polyvinylchloride tubes. The results of trial sequential analysis suggest the need for further trials and meta-analysis to compare other intubation outcomes associated with the two devices. TRIAL REGISTRATION: PROSPERO CRD42020197670.

Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts.

BACKGROUND/PURPOSE: Porphyromonas gingivalis is an oral pathogen associated with periodontal diseases. P. gingivalis GroEL protein is a stimulator of inflammatory cytokines in macrophages. This study inspected effects of P. gingivalis GroEL protein on production of interleukin (IL)-6 and IL-8 by human osteoblasts. METHODS: Viability of GroEL-treated osteoblasts was analyzed with 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Secretion of IL-6 and IL-8 was analyzed using the enzyme-linked immunosorbent assay. Levels of mRNA were analyzed using the reverse transcription and real-time polymerase chain reaction. The antioxidant (curcumin), the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and the c-Jun N-terminal kinase (JNK) inhibitor (SP600125) were employed to elucidate possible signaling pathways involved. RESULTS: Treatment with GroEL did not affect morphology and viability of osteoblasts. GroEL significantly induced the secretion of IL-6 and IL-8 by osteoblasts in a concentration-dependent pattern. Moreover, the mRNA levels of IL-6 and IL-8 were stimulated by GroEL. The application of SP600125 (10 µM) significantly suppressed the induction of IL-6 and IL-8 by GroEL-treated cells. However, curcumin (20 µM) and SB203580 (20 µM) only down-regulated the stimulatory effects of GroEL on IL-6. CONCLUSION: GroEL protein stimulated the inflammatory reaction of osteoblasts, probably through the activation of p38 MAPK or JNK pathway. The findings suggest that P. gingivalis GroEL may influence the immune functions of osteoblasts and endanger the periodontal health.

Digit Force Controls and Corresponding Brain Activities in Finger Pressing Performance: A Comparison Between Older Adults and Young Individuals.

This study aims toward an investigation and comparison of the digital force control and the brain activities of older adults and young groups during digital pressing tasks. A total of 15 young and 15 older adults were asked to perform force ramp tasks at different force levels with a custom pressing system. Near-infrared spectroscopy was used to collect the brain activities in the prefrontal cortex and primary motor area. The results showed that the force independence and hand function of the older adults were worse than that of the young adults. The cortical activations in the older adults were higher than those in the young group during the tasks. A significant hemodynamic between-group response and mild negative correlations between brain activation and force independence ability were found. Older adults showed poor force independence ability and manual dexterity and required additional brain activity to compensate for the degeneration.

Effects of health-information-based diabetes shared care program participation on preventable hospitalizations in Taiwan.

BACKGROUND: Taiwan's Diabetes Shared Care Program has been implemented since 2012, and the health information system plays a vital role in supporting most services of this program. However, little is known regarding the effectiveness of this information-based program. Therefore, this study investigated the effects of the participation of the Diabetes Shared Care Program on preventable hospitalizations. METHODS: This longitudinal study examined the data of health-care claims from 2011 to 2014 obtained from the diabetes mellitus health database. Patients with diabetes aged ≥18 years were included. Preventable hospitalizations were identified on the basis of prevention quality indicators developed for administrative data by the US Agency for Healthcare Research and Quality. A multilevel logistic regression was performed to examine the effects of the participation of the Diabetes Shared Care Program on preventable hospitalizations after adjustment for other variables. Analyses were conducted in late 2018. RESULTS: A medium level of participation (p = 0.05), age between 40 and 64 years(p < 0.0001), and absence of a catastrophic illness(p < 0.0001) were associated with a lower probability of having a preventable hospitalization. Male sex(p < 0.0001), age ≥ 65 years(p = 0.0203), low income level(p < 0.0001), living in the Southern division(p = 0.0106), and presence of many comorbidities(p < 0.0001) were associated with a higher probability of having a preventable hospitalization after adjustment for characteristics at the individual and county levels. CONCLUSIONS: The health information system records patients' medical history, monitors quality of care, schedules patient follow-ups, and reminds case managers to provide timely health education. This health-information-based Diabetes Shared Care Program is associated with better quality care of ambulatory, so it should be promoted on a broader scale.

Differences in laser-Doppler indices between skin-surface measurement sites in subjects with diabetes.

This study performed laser-Doppler flowmetry (LDF) measurements with the aim of identifying differences in diabetes-induced microcirculatory-blood-flow (MBF) responses between the following skin surface measurement sites: an acupoint around the wrist, an acupoint around the ankle, and a nearby nonacupoint around the ankle. The 67 study subjects were assigned to diabetic, prediabetic, and healthy groups according to the results of oral glucose tolerance tests. Beat-to-beat and spectral analyses were applied to the LDF waveform to obtain the foot delay time (FDT), the flow rise time (FRT), and the relative energy contributions (RECs) in five frequency bands. FRT and FDT were significantly shorter and the RECs of the endothelial-, neural-, and myogenic-related frequency bands were significantly smaller in the diabetic group than in the control group at the acupoint around the ankle, but there were no such prominent differences at the other sites. The acupoint around the ankle was better than the nearby nonacupoint and the acupoint around the wrist for distinguishing the age-matched diabetic, prediabetic, and healthy subjects. These findings imply that when monitoring diabetes-induced MBF responses, the measurement locations should be chosen carefully in order to minimize interference effects and to improve the ability to distinguish subjects with different conditions.

Combining laser-Doppler flowmetry measurements with spectral analysis to study different microcirculatory effects in human prediabetic and diabetic subjects.

We aimed to identify the microcirculatory regulatory mechanisms in diabetic and prediabetic humans using a noninvasive method combining spectral analysis with laser-Doppler flowmetry (LDF) measurements on the skin surface. LDF signals were measured by a moorVMS-LDF device to measure the microcirculatory blood flow flux with a time constant of 0.001 s, a cutoff frequency of 14.9 kHz, and a sampling frequency of 40 Hz. The laser operating wavelength and output power were 400-700 nm and 6 mW, respectively. LDF signals were obtained noninvasively in 115 subjects, who were assigned to three groups (diabetic, prediabetic, and normal) according to the results of the oral glucose tolerance tests. A Morlet mother wavelet transform was applied to the measured 20-min LDF signals, and periodic oscillations with five characteristic frequency peaks were obtained within the following frequency bands: 0.0095-0.02, 0.02-0.06, 0.06-0.15, 0.15-0.4, and 0.4-1.6 Hz (defined as FR1-FR5), respectively. The relative energy contribution (REC) of FR1 was significantly smaller (by using the Kruskal-Wallis test followed by Dunn's multiple-comparison tests) in diabetic subjects than in normal subjects. The REC of FR2-FR3 was significantly smaller in diabetic and prediabetic subjects than in normal subjects. The REC of FR1-FR3 from normal to prediabetic and diabetic subjects showed a progressive decrease. The present findings may aid in the development of a noninvasive method for the early detection of prediabetes and the monitoring of disease progression. This may be useful in preventing disease progression and reducing the risk of concomitant end-organ damage.

Genomic and transcriptomic comparison of nucleotide variations for insights into bruchid resistance of mungbean (Vigna radiata [L.] R. Wilczek).

BACKGROUND: Mungbean (Vigna radiata [L.] R. Wilczek) is an important legume crop with high nutritional value in South and Southeast Asia. The crop plant is susceptible to a storage pest caused by bruchids (Callosobruchus spp.). Some wild and cultivated mungbean accessions show resistance to bruchids. Genomic and transcriptomic comparison of bruchid-resistant and -susceptible mungbean could reveal bruchid-resistant genes (Br) for this pest and give insights into the bruchid resistance of mungbean. RESULTS: Flow cytometry showed that the genome size varied by 61 Mb (mega base pairs) among the tested mungbean accessions. Next generation sequencing followed by de novo assembly of the genome of the bruchid-resistant recombinant inbred line 59 (RIL59) revealed more than 42,000 genes. Transcriptomic comparison of bruchid-resistant and -susceptible parental lines and their offspring identified 91 differentially expressed genes (DEGs) classified into 17 major and 74 minor bruchid-resistance-associated genes. We found 408 nucleotide variations (NVs) between bruchid-resistant and -susceptible lines in regions spanning 2 kb (kilo base pairs) of the promoters of 68 DEGs. Furthermore, 282 NVs were identified on exons of 148 sequence-changed-protein genes (SCPs). DEGs and SCPs comprised genes involved in resistant-related, transposable elements (TEs) and conserved metabolic pathways. A large number of these genes were mapped to a region on chromosome 5. Molecular markers designed for variants of putative bruchid-resistance-associated genes were highly diagnostic for the bruchid-resistant genotype. CONCLUSIONS: In addition to identifying bruchid-resistance-associated genes, we found that conserved metabolism and TEs may be modifier factors for bruchid resistance of mungbean. The genome sequence of a bruchid-resistant inbred line, candidate genes and sequence variations in promoter regions and exons putatively conditioning resistance as well as markers detecting these variants could be used for development of bruchid-resistant mungbean varieties.

Identification of single nucleotide polymorphism markers associated with resistance to bruchids (Callosobruchus spp.) in wild mungbean (Vigna radiata var. sublobata) and cultivated V. radiata through genotyping by sequencing and quantitative trait locus analysis.

BACKGROUND: Bruchid beetles are an important storage pest of grain legumes. Callosobruchus sp. infect mungbean (Vigna radiata) at low levels in the field, multiply during grain storage and can destroy seed stocks in a few months. Resistance against bruchid beetles has been found in wild mungbean V. radiata var. sublobata TC1966 and in cultivated mungbean line V2802. RESULTS: Bruchid resistance data were obtained from recombinant inbred line populations TC1966 (V. radiata var. sublobata) × NM92 (F12) and V2802 (V. radiata) × NM94 (F7). More than 6,000 single nucleotide polymorphic markers were generated through genotyping by sequencing (GBS) for each of these populations and were used to map bruchid resistance genes. One highly significant quantitative trait locus (QTL) associated with bruchid resistance was mapped to chromosome 5 on genetic maps of both populations, suggesting that TC1966 and V2802 contain the same resistance locus. Co-segregation of all markers associated with resistance indicated the presence of only one major resistance QTL on chromosome 5, while QTL analysis based on physical map positions of the markers suggested the presence of multiple QTLs on different chromosomes. The diagnostic capacity of the identified molecular markers located in the QTL to correctly predict resistance was up to 100 %. CONCLUSIONS: Molecular markers tightly linked to bruchid resistance loci of two different mungbean resistance sources were developed and validated. These markers are highly useful for developing resistant lines.

The effect of red light and far-red light conditions on secondary metabolism in agarwood.

BACKGROUND: Agarwood, a heartwood derived from Aquilaria trees, is a valuable commodity that has seen prevalent use among many cultures. In particular, it is widely used in herbal medicine and many compounds in agarwood are known to exhibit medicinal properties. Although there exists much research into medicinal herbs and extraction of high value compounds, few have focused on increasing the quantity of target compounds through stimulation of its related pathways in this species. RESULTS: In this study, we observed that cucurbitacin yield can be increased through the use of different light conditions to stimulate related pathways and conducted three types of high-throughput sequencing experiments in order to study the effect of light conditions on secondary metabolism in agarwood. We constructed genome-wide profiles of RNA expression, small RNA, and DNA methylation under red light and far-red light conditions. With these profiles, we identified a set of small RNA which potentially regulates gene expression via the RNA-directed DNA methylation pathway. CONCLUSIONS: We demonstrate that light conditions can be used to stimulate pathways related to secondary metabolism, increasing the yield of cucurbitacins. The genome-wide expression and methylation profiles from our study provide insight into the effect of light on gene expression for secondary metabolism in agarwood and provide compelling new candidates towards the study of functional secondary metabolic components.

Diastereoselective Synthesis of Fluorine-Containing Pyrrolizidines via Triphenylcarbenium Tetrafluoroborate-Promoted Carbofluorination of N-3-Arylpropargylpyrrolidine-Tethered Tertiary Allylic Alcohols.

Inexpensive and air stable triphenylcarbenium tetrafluoroborate efficiently promoted the carbofluorination of N-arylpropargylpyrrolidines bearing a tertiary allylic alcohol tether at the 2-position of the pyrrolidine ring to provide 1-isobutenyl-2-(fluoro(phenyl)methylenylhexahydro-1H-pyrrolizidines in a stereoselective fashion. When subjected to bis(trifluoromethane)sulfonamide, the same substrates underwent cycloisomerization reaction within minutes to generate 1-isobutenyl-2-benzoylhexahydro-1H-pyrrolizidines with excellent stereoselectivity.

Is the Control of Applied Digital Forces During Natural Five-digit Grasping Affected by Carpal Tunnel Syndrome?

BACKGROUND: The impaired sensory function of the hand induced by carpal tunnel syndrome (CTS) is known to disturb dexterous manipulations. However, force control during daily grasping configuration among the five digits has not been a prominent focus of study. Because grasping is so important to normal function and use of a hand, it is important to understand how sensory changes in CTS affect the digit force of natural grasp. QUESTIONS/PURPOSES: We therefore examined the altered patterns of digit forces applied during natural five-digit grasping in patients with CTS and compared them with those seen in control subjects without CTS. We hypothesized that the patients with CTS will grasp by applying larger forces with lowered pair correlations and more force variability of the involved digits than the control subjects. Specifically, we asked: (1) Is there a difference between patients with CTS and control subjects in applied force by digits during lift-hold-lower task? (2) Is there a difference in force correlation coefficient of the digit pairs? (3) Are there force variability differences during the holding phase? METHODS: We evaluated 15 female patients with CTS and 15 control subjects matched for age, gender, and hand dominance. The applied radial forces (Fr) of the five digits were recorded by respective force transducers on a cylinder simulator during the lift-hold-lower task with natural grasping. The movement phases of the task were determined by a video-based motion capture system. RESULTS: The applied forces of the thumb in patients with CTS (7 ± 0.8 N; 95% CI, 7.2-7.4 N) versus control subjects (5 ± 0.8 N; 95% CI, 5.1-5.3 N) and the index finger in patients with CTS (3 ± 0.3 N; 95% CI, 3.2-3.3 N) versus control subjects (2 ± 0.3 N; 95% CI, 2.2-2.3 N) observed throughout most of the task were larger in the CTS group (p ranges 0.035-0.050 for thumb and 0.016-0.050 for index finger). In addition, the applied force of the middle finger in patients with CTS (1 ± 0.1 N; 95% CI, 1.3-1.4 N) versus the control subjects (2 ± 0.2 N; 95% CI, 1.9-2.0 N) during the lowering phase was larger in CTS group (p ranges 0.039-0.050). The force correlations of the thumb-middle finger observed during the lowering phase in the patients with CTS (0.8 ± 0.2; 95% CI, 0.6-0.9) versus the control subjects (0.9 ± 0.1; 95% CI, 0.8-1.0; p = 0.04) were weaker in the CTS group. The thumb-little finger during holding in the patients with CTS (0.5 ± 0.2; 95% CI, 0.3-0.7) versus the control subjects (0.8 ± 0.2; 95% CI, 0.6-0.9; p = 0.02), and the lowering phase in the patients with CTS (0.6 ± 0.2; 95% CI, 0.3-0.8) versus the control subjects (0.9 ± 0.1; 95% CI, 0.8-1.0; p = 0.01) also were weaker. The force variabilities of patients with CTS were greater in the CTS group than in the control subjects: in the thumb ([0.26 ± 0.11 N, 95% CI, 0.20-0.32 N] versus [0.19 ± 0.06 N; 95% CI, 0.16-0.22 N], p = 0.03); index finger ([0.09 ± 0.07 N; 95% CI, 0.05-0.13 N] versus [0.05 ± 0.03 N; 95% CI, 0.04-0.07 N], p = 0.03); middle finger ([0.06 ± 0.04 N; 95% CI, 0.04-0.08 N] versus [0.03 ± 0.01 N; 95% CI, 0.02-0.04 N], p = 0.02), and ring finger ([0.04 ± 0.03 N; 95% CI, 0.20-0.06 N] versus [0.02 ± 0.01 N; 95% CI, 0.02-0.02 N], p = 0.01). CONCLUSIONS: Patients with CTS grasped with greater digit force associated with weaker correlation and higher variability on specific digits in different task demands. These altered patterns in daily grasping may lead to secondary problems, which will need to be assessed in future studies with this model to see if they are reversible in patients undergoing carpal tunnel release. CLINICAL RELEVANCE: The current results helped to identify altered patterns of grasping force during simulated daily function in patients with CTS and to provide the clinician with potential information that might help guide the rehabilitation of grasp in these patients.

Exponential H ∞ Synchronization of Chaotic Cryptosystems Using an Improved Genetic Algorithm.

This paper presents a systematic design methodology for neural-network- (NN-) based secure communications in multiple time-delay chaotic (MTDC) systems with optimal H ∞ performance and cryptography. On the basis of the Improved Genetic Algorithm (IGA), which is demonstrated to have better performance than that of a traditional GA, a model-based fuzzy controller is then synthesized to stabilize the MTDC systems. A fuzzy controller is synthesized to not only realize the exponential synchronization, but also achieve optimal H ∞ performance by minimizing the disturbance attenuation level. Furthermore, the error of the recovered message is stated by using the n-shift cipher and key. Finally, a numerical example with simulations is given to demonstrate the effectiveness of our approach.

Identification of cucurbitacins and assembly of a draft genome for Aquilaria agallocha.

BACKGROUND: Agarwood is derived from Aquilaria trees, the trade of which has come under strict control with a listing in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Many secondary metabolites of agarwood are known to have medicinal value to humans, including compounds that have been shown to elicit sedative effects and exhibit anti-cancer properties. However, little is known about the genome, transcriptome, and the biosynthetic pathways responsible for producing such secondary metabolites in agarwood. RESULTS: In this study, we present a draft genome and a putative pathway for cucurbitacin E and I, compounds with known medicinal value, from in vitro Aquilaria agallocha agarwood. DNA and RNA data are utilized to annotate many genes and protein functions in the draft genome. The expression changes for cucurbitacin E and I are shown to be consistent with known responses of A. agallocha to biotic stress and a set of homologous genes in Arabidopsis thaliana related to cucurbitacin bio-synthesis is presented and validated through qRT-PCR. CONCLUSIONS: This study is the first attempt to identify cucurbitacin E and I from in vitro agarwood and the first draft genome for any species of Aquilaria. The results of this study will aid in future investigations of secondary metabolite pathways in Aquilaria and other non-model medicinal plants.

Complexity analysis of beat-to-beat skin-surface laser-Doppler signals in diabetic subjects.

MOTIVATIONS: This study performed skin-surface laser-Doppler flowmetry (LDF) measurements with the aim of verifying if complexity analysis applied to the beat-to-beat LDF waveform index can be used to discriminate diabetic, prediabetic, and normoglycemic subjects. METHODS: Sixty-six subjects were assigned to three age-matched groups according to the results of oral glucose tolerance tests. Beat-to-beat analysis was performed on the pulsatile LDF waveform to obtain the pulse-to-mean ratio (AD) and pulse width (PW), and then approximate-entropy (ApEn) values for their 20-minute index sequences were calculated to evaluate the signal complexity. RESULTS: AD and PW did not differ significantly among the three study groups. ApEn values of AD and PW were significantly larger and marginally larger, respectively, in the diabetic group than in the prediabetic and normoglycemic groups. CONCLUSION: These results indicate the presence of significant differences in ApEn indexes among diabetic, prediabetic, and normoglycemic subjects. The presence of increased complexity in the LDF index sequence may be partly attributed to the adaptability of the microcirculatory regulatory activities or the impairment of the homeostasis mechanism of microcirculatory-blood-flow perfusion. The present findings may be pertinent to the early detection of the diabetes-induced impairment of this perfusion.

Clinical manifestations of alpine pit viper (Trimeresurus gracilis) bites.

INTRODUCTION: The alpine pit viper, Trimeresurus gracilis, is an endemic species in Taiwan. The incidence of human envenoming is rare. CASE SUMMARIES: We present three events in two patients bitten by Trimeresurus gracilis. In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each. DISCUSSION: Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling. CONCLUSIONS: The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Influence of altered torsional stiffness through sole modification of air pressure shoes on lower extremity biomechanical behaviour during side-step cutting maneuvers.

Directional changes in cutting maneuvers are critical in sports, where shoe torsional stiffness (STS) is an important factor. Shoes are designed based on different constructions and movement patterns. Hence, it is unclear how adjustable spacers into the sole constructions of air pressure chambers (APC) affect the STS in side-step cutting. Therefore, this study investigated the effects of altered STS through adjustable sole spacers on ground reaction force (GRF) and ankle and knee joint moments in side-step cutting. Seventeen healthy recreational athletes performed side-step cutting with experimental conditions including (i) barefoot (BF), (ii) unaltered shoes (UAS): soles consisting of APC, and (iii) altered shoes (AS): modified UAS by inserting elastomeric spacers into cavities formed by APC. Mechanical and biomechanical variables were measured. Significant differences were revealed across shoe conditions for impact peak (p = 0.009) and impulse (p = 0.018) in vertical GRF, time to achieve peak braking (p = 0.004), and peak propulsion (p = 0.025) for anterior-posterior GRF in ANOVA test. No significant differences were observed in GRF peaks and impulses between UAS and AS except for a trend of differences in impact peak (p = 0.087) for vertical GRF. At the ankle and knee joint, peak ankle power absorption (p = 0.019), peak knee internal rotation moment (p = 0.042), peak knee extension moment (p = 0.001), peak knee flexion moment (0.000), peak knee power absorption (p = 0.047) showed significant difference across three shoe conditions. However, no significant differences between the UAS and AS were noticed for peak joint moments and power. Altered shoe torsional stiffness did not significantly affect the peak forces and peak ankle and knee joint moments or powers; hence sole adjustment did not influence the cutting performance. This study might be insightful in sports footwear design, and adjusting shoe torsional stiffness by sole modification might be advantageous for athletes playing sports with cutting maneuvers to reduce the risk of injuries by controlling the twisting force at the ankle that frequently happens during cutting maneuvers.