Attention and Capacity Limits in Perception: A Cellular Metabolism Account.

Limits on perceptual capacity result in various phenomena of inattentional blindness. Here we propose a neurophysiological account attributing these perceptual capacity limits directly to limits on cerebral cellular metabolism. We hypothesized that overall cerebral energy supply remains constant, regardless of overall mental processing demands; therefore, an attention mechanism is required to regulate limited cellular metabolism levels in line with attended task demands. Increased perceptual load in a task (imposing a greater demand on neural computations) should thus result in increased metabolism underlying attended processing, and reduced metabolism mediating unattended processing. We tested this prediction measuring oxidation states of cytochrome c oxidase (oxCCO), an intracellular marker of cellular metabolism. Broadband near-infrared spectroscopy was used to record oxCCO levels from human visual cortex while participants (both sexes) performed a rapid sequential visual search task under either high perceptual load (complex feature-conjunction search) or low load (feature pop-out search). A task-irrelevant, peripheral checkerboard was presented on a random half of trials. Our findings showed that oxCCO levels in visual cortex regions responsive to the attended-task stimuli were increased in high versus low perceptual load, whereas oxCCO levels related to unattended processing were significantly reduced. A negative temporal correlation of these load effects further supported our metabolism trade-off account. These results demonstrate an attentional compensation mechanism that regulates cellular metabolism levels according to processing demands. Moreover, they provide novel evidence for the widely held stipulation that overall cerebral metabolism levels remain constant regardless of mental task demand and establish a neurophysiological account for capacity limits in perception.SIGNIFICANCE STATEMENT We investigated whether capacity limits in perception can be explained by the effects of attention on the allocation of limited cellular metabolic energy for perceptual processing. We measured the oxidation state of cytochrome c oxidase, an intracellular measure of metabolism, in human visual cortex during task performance. The results showed increased levels of cellular metabolism associated with attended processing and reduced levels of metabolism underlying unattended processing when the task was more demanding. A temporal correlation between these effects supported an attention-directed metabolism trade-off. These findings support an account for inattentional blindness grounded in cellular biochemistry. They also provide novel evidence for the claim that cerebral processing is limited by a constant energy supply, which thus requires attentional regulation.

Electrocardiographic and genetic characteristics in first degree relatives of hypertrophic cardiomyopathy probands: A descriptive cross-sectional study from Vietnam.

Objectives: In order to study the phenotype-genotype relationship and to better understand the early consequences of the mutation, we would report the spectrum of electrocardiographic and genetic features in the relatives of hypertrophic cardiomyopathy (HCM) patients. Methods: Participants underwent a comprehensive clinical assessment, electrocardiography, standardized and echocardiography and genetic testing. In probands, next-generation sequencing was performed using the gene panel associated with HCM, while in relatives, Sanger sequencing was used to screen for mutations identified in their individual probands. Results: A total of 84 participants were included in this study. The interventricular septal and posterior wall thickness was highest in the G+/LVH+ group, followed by the G+/LVH- group, and was lowest in G-/LVH- group. Compared to the normal control group, the pathologic Q wave was statistically more prevalent in the G+/LVH- group. The prevalence of repolarization abnormalities and major abnormalities was highest in the G+/LVH+ group, followed by the G+/LVH- group, and lowest in G-/LVH- group. Conclusion: Our results suggested that sarcomere mutations have early consequences on myocardial biology. These findings suggest the possibility of implementing a mutation carrier detection model within families affected by HCM, where ECG could play a central role when combined with other relevant clinical factors. Longitudinal studies on a cohort of G+/LVH- patients are required.

Distribution and 24-hour transition of SCAI shock stages and their association with 30-day mortality in acute myocardial infarction.

The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification has been shown to predict mortality in acute myocardial infarction (AMI). However, data on the transition of SCAI stages and their association with mortality after AMI are limited. All patients with AMI admitted to Vietnam National Heart Institute between August 2022 and February 2023 were classified into SCAI stages A, B, and C/D/E at admission and were reevaluated in 24 hours. We used Kaplan-Meier estimate and multivariable Cox regression analysis to assess the association between SCAI stages transition and 30-day mortality. We included 139 patients (median age 69 years, 29.5% female). On admission, 50.4%, 20.1%, and 29.5% of patients were classified as SCAI stage A, B, and C/D/E, respectively. The proportion of patients whose SCAI stage improved, remained stable, or worsened after 24 hours was 14.4%, 66.2%, and 19.4%, respectively. The 30-day mortality in patients with initial SCAI stages A, B, and C/D/E on admission was 2.9%, 21.4%, and 61.0%, respectively (P < .001). The 30-day mortality was 2.4% for patients with baseline SCAI stage A/B who remained unchanged or improved, 30.0% for patients with baseline SCAI stage C/D/E who remained unchanged or improved, and 92.6% for patients with SCAI stage B/C/D/E who worsened at 24 hours after admission (log-rank P < .001). In patients with AMI, evaluating the SCAI stage shock stage on admission and reevaluating after 24 hours added more information about 30-day mortality.

Effect of Force Field Resolution on Membrane Mechanical Response and Mechanoporation Damage under Deformation Simulations.

Damage induced by transient disruption and mechanoporation in an intact cell membrane is a vital nanoscale biomechanical mechanism that critically affects cell viability. To complement experimental studies of mechanical membrane damage and disruption, molecular dynamics (MD) simulations have been performed at different force field resolutions, each of which follows different parameterization strategies and thus may influence the properties and dynamics of membrane systems. Therefore, the current study performed tensile deformation MD simulations of bilayer membranes using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) models to investigate how the damage biomechanics differs across atomistic and coarse-grained (CG) simulations. The mechanical response and mechanoporation damage were qualitatively similar but quantitatively different in the three models, including some progressive changes based on the coarse-graining level. The membranes yielded and reached ultimate strength at similar strains; however, the coarser systems exhibited lower average yield stresses and failure strains. The average failure strain in the UA model was approximately 7% lower than the AA, and the CG-M was 20% lower than UA and 27% lower than AA. The CG systems also nucleated a higher number of pores and larger pores, which resulted in higher damage during the deformation process. Overall, the study provides insight on the impact of force field-a critical factor in modeling biomolecular systems and their interactions-in inspecting membrane mechanosensitive responses and serves as a reference for justifying the appropriate force field for future studies of more complex membranes and more diverse biomolecular assemblies.

Efficacy and safety of zero-fluoroscopy ablation of ventricular arrhythmias originating from the right ventricular outflow tract: Comparison with fluoroscopy-guided ablation without a three-dimensional electroanatomic mapping system.

Background: Radiofrequency catheter ablation is the preferred treatment choice for ventricular arrhythmias (VAs) originating from right ventricular outflow tract (RVOT) in symptomatic patients and is usually performed under fluoroscopy guidance. Zero-fluoroscopy (ZF) ablations using 3D mapping system applied for treatment of various types of arrhythmias are trending and practiced in many centers around the world, but rarely done in Vietnam. The objective of this study was to evaluate the efficacy and safety of zero-fluoroscopy ablation of RVOT VAs, compared with fluoroscopy-guided ablation without a 3D electroanatomic mapping (EAM) system. Methods and Results: We conducted a nonrandomized, prospective single-center study including 114 patients with RVOT VAs that had electrocardiographic features of typical left bundle branch block, inferior axis QRS morphology, and a precordial transition ≥ V3, from May 2020 to July 2022. The patients were assigned (without randomization) to two different approaches of either zero-fluoroscopy ablation under the guidance of the Ensite system (ZF group) or fluoroscopy-guided ablation without a 3D EAM (fluoroscopy group) in a 1:1 ratio. After a follow-up time of 5.0 ± 4.9 months and 6.9 ± 9.3 months in the ZF and fluoroscopy groups, respectively, the results showed a higher success rate in the fluoroscopy group than in the complete ZF group (87.3% vs 86.8%), although the difference was not statistically significant. No major complication was noted in both the groups. Conclusion: ZF ablation for RVOT VAs can be done safely and effectively using the 3D electroanatomic mapping system. The results of ZF approach are comparable to that of the fluoroscopy-guided approach without a 3D EAM system.

In silico validation revealed the role of SCN5A mutations and their genotype-phenotype correlations in Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a rare genetic disease that causes sudden cardiac death (SCD) and arrhythmia. SCN5A pathogenic variants (about 30% of diagnosed patients) are responsible for BrS. AIMS: Lack of knowledge regarding molecular characteristics and the correlation between genotype and phenotype interfere with the risk stratification and finding the optimal treatment in Vietnam. Therefore, we identified SCN5A variants and evaluated the genotype-phenotype correlation of BrS on 117 Vietnamese probands. MATERIALS AND METHODS: The clinical characteristics and blood samples of BrS patients were collected. To determine SCN5A variants, Sanger sequencing was conducted, and subsequently, these variants were analyzed by bioinformatic tools. RESULTS: In this cohort, the overall rate of detected variants in SCN5A was 25.6%, which could include both pathogenic and benign variants. In genetic testing, 21 SCN5A variants were identified, including eight novels and 15 published variants. Multiple bioinformatic tools were used to predict variant effect with c.551A>G, c.1890+14G>A, c.3338C>T, c.3578G>A, and c.5484C>T as benign, while other variants were predicted as disease-causing. The family history of SCD (risk ratio [RR] = 4.324, 95% CI: 2.290-8.269, p < 0.001), syncope (RR = 3.147, 95% CI: 1.668-5.982, p = 0.0004), and ventricular tachycardia/ventricular fibrillation (RR = 3.406, 95% CI: 1.722-5.400, p = 0.0035) presented a significantly higher risk in the SCN5A (+) group, consisting of individuals carrying any variant in the SCN5A gene, compared to SCN5A (-) individuals. CONCLUSION: The results contribute to clarifying the impact of SCN5A variants on these phenotypes. Further follow-up studies need to be carried out to understand the functional effects of these SCN5A variants on the severity of BrS.

Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay.

Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.

Identification of Schistosoma mansoni miracidia attractant candidates in infected Biomphalaria glabrata using behaviour-guided comparative proteomics.

Schistosomiasis, caused by infection with Schistosoma digenetic trematodes, is one of the deadliest neglected tropical diseases in the world. The Schistosoma lifecycle involves the miracidial infection of an intermediate freshwater snail host, such as Biomphalaria glabrata. Dispersing snail host-derived Schistosoma miracidia attractants has been considered a method of minimising intermediate host infections and, by extension, human schistosomiasis. The attractiveness of B. glabrata to miracidia is known to be reduced following infection; however, the relationship between duration of infection and attractiveness is unclear. Excretory-secretory proteins (ESPs) most abundant in attractive snail conditioned water (SCW) are key candidates to function as miracidia attractants. This study analysed SCW from B. glabrata that were naïve (uninfected) and at different time-points post-miracidia exposure (PME; 16h, 1-week, 2-weeks and 3-weeks PME) to identify candidate ESPs mediating Schistosoma mansoni miracidia behaviour change, including aggregation and chemoklinokinesis behaviour (random motion, including slowdown and increased turning rate and magnitude). Miracidia behaviour change was only observed post-addition of naïve and 3W-PME SCW, with other treatments inducing significantly weaker behaviour changes. Therefore, ESPs were considered attractant candidates if they were shared between naïve and 3W-PME SCW (or exclusive to the former), contained a predicted N-terminal signal peptide and displayed low identity (<50%) to known proteins outside of the Biomphalaria genus. Using these criteria, a total of 6 ESP attractant candidates were identified, including acetylcholine binding protein-like proteins and uncharacterised proteins. Tissue-specific RNA-seq analysis of the genes encoding these 6 ESPs indicated relatively high gene expression within various B. glabrata tissues, including the foot, mantle and kidney. Acetylcholine binding protein-like proteins were highly promising due to their high abundance in naïve and 3W-PME SCW, high specificity to B. glabrata and high expression in the ovotestis, from which attractants have been previously identified. In summary, this study used proteomics, guided by behavioural assays, to identify miracidia attractant candidates that should be further investigated as potential biocontrols to disrupt miracidia infection and minimise schistosomiasis.

Identification of Putative Neuropeptides That Alter the Behaviour of Schistosoma mansoni Cercariae.

Elucidating the infectivity of Schistosoma mansoni, one of the main etiological agents of human schistosomiasis, requires an improved understanding of the behavioural mechanisms of cercariae, the non-feeding mammalian infective stage. This study investigated the presence and effect of cercariae-derived putative neuropeptides on cercarial behaviour when applied externally. Cercariae were peptidomically analysed and 11 neuropeptide precursor proteins, all of which were specific to the Schistosoma genus and most of which highly expressed in the cercarial stage, were identified in cercariae for the first time. Protein-protein interaction analysis predicted the interaction of various neuropeptide precursors (e.g., Sm-npp-30, Sm-npp-33, Sm-npp-35) with cercarial structural proteins (e.g., myosin heavy chain and titin). In total, nine putative neuropeptides, selected based on their high hydrophobicity and small size (~1 kilodalton), were tested on cercariae (3 mg/mL) in acute exposure (1 min) and prolonged exposure (360 min) behavioural bioassays. The peptides AAYMDLPW-NH2, NRKIDQSFYSYY-NH2, FLLALPSP-OH, and NYLWDTRL-NH2 stimulated acute increases in cercarial spinning, stopping, and directional change during active states. However, only NRKIDQSFYSYY-NH2 caused the same behavioural changes at a lower concentration (0.1 mg/mL). After prolonged exposure, AAYMDLPW-NH2 and NYLWDTRL-NH2 caused increasing passive behaviour and NRKIDQSFYSYY-NH2 caused increasing body-first and head-pulling movements. These findings characterise behaviour-altering novel putative neuropeptides, which may inform future biocontrol innovations to prevent human schistosomiasis.

Advancing global equity in cardiac care as cardiac implantable electronic device reuse comes of age.

A nation's health and economic development are inextricably and synergistically connected. Stark differences exist between wealthy and developing nations in the use of cardiac implantable electronic devices (CIEDs). Cardiovascular disease is now the leading cause of death in low- and middle-income countries (LMIC), with a significant burden from rhythm-related diseases. As science, technology, education, and regulatory frameworks have improved, CIED recycling for exportation and reuse in LMIC has become possible and primed for widespread adoption. In our manuscript, we outline the science and regulatory pathways regarding CIED reuse. We propose a pathway to advance this technology that includes creating a task force to establish standards for CIED reuse, leveraging professional organizations in areas of need to foster the professional skills for CIED reuse, collaborating with regulatory agencies to create more efficient regulatory expectations and bring the concept to scale, and establishing a global CIED reuse registry for quality assurance and future science.

Analysis of COVID-19 on Diagnosis, Vaccine, Treatment, and Pathogenesis with Clinical Scenarios.

As the world continues to suffer from an ever-growing number of confirmed cases of the SARS-CoV-2 novel coronavirus, researchers are at the forefront of developing the best plan to overcome this pandemic through analyzing the pathogenesis, prevention, and treatment options pertaining to the virus. In the midst of a pandemic, the main route for detection of the virus has been conducting antigen tests for rapid results, using qRT-PCR, and conducting more accurate molecular tests, using rRT-PCR, on samples from patients. Most common treatments for those infected with COVID-19 include Remdesivir, an antiviral, dexamethasone, a steroid, and rarely, monoclonal antibody treatments. Although these treatments exist and are used commonly in hospitals all around the globe, clinicians often challenge the efficacy and benefit of these remedies for the patient. Furthermore, targeted therapies largely focus on interfering with or reducing the binding of viral receptors and host cell receptors affected by the SARS-CoV-2 novel coronavirus. In addition to treatment, the most efficacious method of preventing the spread of COVID-19 is the development of multiple vaccines that have been distributed as well as the development of multiple vaccine candidates that are proving hopeful in preventing severe symptoms of the virus. The exaggerated immune response to the virus proves to be a worrying complication due to widespread inflammation and subsequent clinical sequela. The medical and scientific community as a whole will be expected to respond with the latest in technology and research, and further studies into the pathogenesis, clinical implications, identification, diagnosis, and treatment of COVID-19 will push society past this pandemic.

Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment.

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

Fluorescence-based methods for measuring target interference by CRISPR-Cas systems.

Type I, II, and V CRISPR-Cas systems are RNA-guided dsDNA targeting defense mechanisms found in bacteria and archaea. During CRISPR interference, Cas effectors use CRISPR-derived RNAs (crRNAs) as guides to bind complementary sequences in foreign dsDNA, leading to the cleavage and destruction of the DNA target. Mutations within the target or in the protospacer adjacent motif can reduce the level of CRISPR interference, although the level of defect is dependent on the type and position of the mutation, as well as the guide sequence of the crRNA. Given the importance of Cas effectors in host defense and for biotechnology tools, there has been considerable interest in developing sensitive methods for detecting Cas effector activity through CRISPR interference. In this chapter, we describe an in vivo fluorescence-based method for monitoring plasmid interference in Escherichia coli. This approach uses a green fluorescent protein reporter to monitor varying plasmid levels within bacterial colonies, or to measure the rate of plasmid-loss in bacterial populations over time. We demonstrate the use of this simple plasmid-loss assay for both chromosomally integrated and plasmid-borne CRISPR-Cas systems.

Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data.

In diffuse optical tomography (DOT), overlapping and multidistance measurements are required to reconstruct depth-resolved images of oxy- ([Formula: see text]) and deoxy- (HHb) hemoglobin concentration changes occurring in the brain. These can be considered an indirect measure of brain activity, under the assumption of intact neurovascular coupling. Broadband systems also allow changes in the redox state of cytochrome c oxidase (oxCCO) to be measured, which can be an important biomarker when neurovascular coupling is impaired. We used DOT to reconstruct images of [Formula: see text], [Formula: see text], and [Formula: see text] from data acquired with a broadband system. Four healthy volunteers were measured while performing a visual stimulation task (4-Hz inverting checkerboard). The broadband system was configured to allow multidistance and overlapping measurements of the participants' visual cortex with 32 channels. A multispectral approach was employed to reconstruct changes in concentration of the three chromophores during the visual stimulation. A clear and focused activation was reconstructed in the left occipital cortex of all participants. The difference between the residuals of the three-chromophore model and of the two-chromophore model (recovering only [Formula: see text] and [Formula: see text]) exhibits a spectrum similar to that of oxCCO. These results form a basis for further studies aimed to further optimize image reconstruction of [Formula: see text].

Immolina, a high-molecular-weight polysaccharide fraction of Spirulina, enhances chemokine expression in human monocytic THP-1 cells.

INTRODUCTION: Spirulina (Spirulina platensis) is a dietary supplement valued for its immune-enhancing properties. We previously reported that the immunostimulatory effect of spirulina can be traced to a high-molecular- weight polysaccharide fraction. This fraction, labeled Immolina, activates nuclear factor kappa-B in human monocytic THP-1 cells and increases expression of proinflammatory cytokines. OBJECTIVE: To characterize further the immunostimulatory effects of Immolina on THP-1 cells, we evaluated its effect on genes encoding the chemokines interleukin (IL)-8, MCP-1, MIP-1alpha, MIP-1beta, IP-10, the cytokines tumor necrosis factor (TNF)-alpha, IL-1beta, and the enzyme cyclo-oxygenase-2 (COX-2). METHODS: THP-1 cells were exposed to concentrations of Immolina ranging from 1 ng/mL to 100 microg/mL and changes in gene expression were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). For comparison, THP-1 cells were activated with 1 ng/mL of TNF-alpha, 10 ng/mL of IL-1beta, or 10 ng/mL of lipopolysaccharide using the same assay conditions. To assess the response of THP-1 cells to Immolina at the protein level, we probed culture supernatants using a cytokine array immunoblot assay. RESULTS: RT-PCR analysis revealed that Immolina dose-dependently increased the expression of all 5 chemokines tested as well as the expression of TNF-alpha, IL-1beta, and COX-2. The cytokine array immunoblot assay revealed an increase in the chemokines IL-8 and MIP-1beta. Thymidine uptake experiments verified that Immolina did not affect the viability and growth rate of THP-1 cells. CONCLUSIONS: The results of the experiments demonstrate that Immolina activates THP-1 cells in a manner that is consistent with the recruitment of diverse populations of leukocytes in response to inflammatory and infectious signals.

Multi-channel multi-distance broadband near-infrared spectroscopy system to measure the spatial response of cellular oxygen metabolism and tissue oxygenation.

We present a multi-channel, multi-distance broadband near-infrared spectroscopy (NIRS) system with the capability of measuring changes in haemoglobin concentrations (Δ[HbO2], Δ[HHb]), oxidation state of cytochrome-c-oxidase (Δ[oxCCO]) and tissue oxygen saturation (TOI) in the adult human brain. The main components of the instrument are two customized spectrographs and two light sources. Each spectrograph is lens-based to improve light throughput, has a grating enhanced to optimise reflection in the near-infrared (NIR) spectral region and uses a front illuminated cooled CCD camera (-70° C) with a square chip dimension of 12.3 x 12.3 mm (512 x 512 pixels). Each light source uses a 50W halogen bulb with a gold plated mirror to increase the intensity of the NIR light. Each light source was connected to a custom-built bifurcated fibre bundle to create two source fibre bundles (3.2 mm diameter each). Each spectrograph received light input from another custom-built fibre bundle comprised of six individual bundles (one with 0.6 mm diameter and the other five with 1.5 mm diameter). All fibre bundles were fixed on a 3D printed optode holder (two light sources x two fibre bundles each = four probes; and two spectrographs x six fibre bundles each = 12 probes) that allowed 24 multi-distance channels across the forehead (six channels at 20 mm, three channels at 30 mm and 15 channels at 35 mm) and six TOI measurements. We demonstrated the use of the system in a cohort of nine healthy adult volunteers during prefrontal cortex functional activation using the Stroop task. We have observed functional responses identified as significant increase in Δ[HbO2], decrease in Δ[HHb] and increase in Δ[oxCCO] in five channels (out of 12), that overlay the left and right dorsolateral prefrontal cortices. There was no observable TOI functional response and we have shown small variations in TOI across different sites within the same subject and within the same site across subjects.

Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo.

The first wearable multi-wavelength technology for functional near-infrared spectroscopy has been developed, based on a custom-built 8-wavelength light emitting diode (LED) source. A lightweight fibreless probe is designed to monitor changes in the concentrations of multiple absorbers (chromophores) in biological tissue, the most dominant of which at near-infrared wavelengths are oxyhemoglobin and deoxyhemoglobin. The use of multiple wavelengths enables signals due to the less dominant chromophores to be more easily distinguished from those due to hemoglobin and thus provides more complete and accurate information about tissue oxygenation, hemodynamics, and metabolism. The spectroscopic probe employs four photodiode detectors coupled to a four-channel charge-to-digital converter which includes a charge integration amplifier and an analogue-to-digital converter (ADC). Use of two parallel charge integrators per detector enables one to accumulate charge while the other is being read out by the ADC, thus facilitating continuous operation without dead time. The detector system has a dynamic range of about 80 dB. The customized source consists of eight LED dies attached to a 2 mm × 2 mm substrate and encapsulated in UV-cured epoxy resin. Switching between dies is performed every 20 ms, synchronized to the detector integration period to within 100 ns. The spectroscopic probe has been designed to be fully compatible with simultaneous electroencephalography measurements. Results are presented from measurements on a phantom and a functional brain activation study on an adult volunteer, and the performance of the spectroscopic probe is shown to be very similar to that of a benchtop broadband spectroscopy system. The multi-wavelength capabilities and portability of this spectroscopic probe will create significant opportunities for in vivo studies in a range of clinical and life science applications.

Ginger extract components suppress induction of chemokine expression in human synoviocytes.

INTRODUCTION: Ginger has a long history of medicinal use, particularly as an anti-inflammatory agent for a wide variety of diseases such as arthritis. Suppression of inflammation in arthritis is attributed to suppression of proinflammatory cytokines and chemokines produced by synoviocytes, chondrocytes, and leukocytes. OBJECTIVE: This study aimed to elucidate the effect of a combination ginger extract and its individual components on chemokine expression in human synoviocytes. METHODS: Human synoviocytes were incubated with 100 microg/mL combination ginger extract (GE) of Alpinia galanga (AG) and Zingiber officinale (ZO); AG extract alone; ZO extract alone; or control media, for 1 hour at 37 degrees C, 5% CO2. Cells were next activated with 1 ng/mL of tumor necrosis factor alpha (TNF-alpha) for 1 hour to determine macrophage chemotactic factor (MCP-1) and interferon-gamma activated protein (IP-10) mRNA levels using reverse transcriptase polymerase chain reaction (RT-PCR). Secreted MCP-1 and IP-10 were quantified by enzyme-linked immunosorbent assay (ELISA) following a 24 hour incubation period. RESULTS: The GE combination was consistently more effective in decreasing chemokine mRNA and chemokine secreted protein levels than its individual components ZO or AG. In comparison, ZO was more effective than AG in suppressing chemokine expression. CONCLUSION: The present study demonstrates that GE inhibits chemokine expression, and that the combination of ZO and AG components acts synergistically. This ginger formulation may be useful for suppressing inflammation due to arthritis.

The effect of silica-containing calcium-phosphate particles on human osteoblasts in vitro.

There is an ongoing need for more effective and less costly bone substitutes. It has previously been proposed that silica-containing bioactive glass would be more effective as a bone repair material because of its physiochemical properties. Three newly synthesized silica-containing bioactive glass formulations, HA-31 (25%), HA-11 (50%), and HA-13 (75%), were tested as biocompatible substrates for the continued proliferation and phenotype expression of human bone cells in vitro. Two currently available bioactive glasses (BioGlass(R), Hydroxyapatite) served as comparisons. The biocompatibility of these bioglasses, as well as their osteoconductive properties, was assessed by employing primary cultures of human osteoblasts and human synoviocytes for 4 days. The results obtained demonstrated that the three new bioglasses enhanced the proliferative response of osteoblasts compared with osteoblasts cultured alone. Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis indicated that osteoblasts retained their phenotypic expression by continued expression of collagen type I and alkaline phosphatase. The newly synthesized preparations of silica-containing bioactive glass did not induce stimulation of proinflammatory markers iNOS and IL-1beta in synoviocytes. In conclusion, the newly synthesized silica-containing bioactive glasses are biocompatible substrate for bone-forming osteoblasts. However, the formulations tested did not show significant advantage over the currently available bioactive glasses in vitro.

An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.

Tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase (COX)-2, and prostaglandin (PG)E-2 play a critical role in the pathophysiology of arthritis. Tumor necrosis factor-alpha mediates induction of other cytokines, COX-2, PGs, and metalloproteinases, which leads to cartilage degradation. We developed an in vitro human synoviocyte assay system for screening inhibitors of proinflammatory mediators in herbal extracts. Synoviocytes (5 x 10(5) cells/well) obtained during primary knee replacement from osteoarthritic patients were incubated with: control media alone or ginger extract (hydroxy-methoxy-phenyl compounds [HAPC]: EV.EXT 77), 1 h before activation with 1 ng/ml TNF-alpha, 10 ng/ml interleukin-1beta, or control media alone at 5% carbon dioxide, 37 degrees C. Cell viability, TNF-alpha, COX-2, PGE-2, nuclear factor kappaB (NF-kappaB), and inhibitory subunit I kappa B-alpha (IkappaB-alpha) expression were analyzed by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, electrophoretic mobility shift assay, and Western blots. Ginger extract-HAPC (100 microg/ml) significantly inhibited the activation of TNF-alpha and COX-2 expression in human synoviocytes as well as suppressed production of TNF-alpha and PGE-2. Inhibition of TNF-alpha and COX-2 activation was accompanied by suppression of NF-kappaB and IkappaB-alpha induction. Using our in vitro assay, we discovered that the ginger extract blocks activation of proinflammatory mediators and its transcriptional regulator suggesting its mode of action. These observations indicate that ginger extract-HAPC offers a complementary and alternative approach to modulate the inflammatory process involved in arthritis.