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Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of zinc transporters and storage mechanisms during cancer progression. Zinc transportation is under the control of two major transporter families: SLC30 (ZnT) for the excretion of zinc and SLC39 (ZIP) for the zinc intake. Additionally, the storage of this essential element is predominantly mediated by metallothioneins (MTs). This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression, with a special focus on cancer. We also compile a summary of clinical trials involving zinc ions. Given the main localization of zinc transporters at the cell membrane, the potential for targeted therapies, including small molecules and monoclonal antibodies, offers promising avenues for future exploration., (© 2023. The Author(s).)

Background: Cancer-associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro-tumourigenic or anti-tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single-cell pan-cancer scale has yet to be established., Methods: We employed a comprehensive single-cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single-Cell Regulatory Network Inference and Clustering and single-cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix-producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments., Results: In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity., Conclusions: Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE., Method: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis., Results: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement ( F  = 25.093, p <.001, R 2 =.065) and positively predicted behavioural disaffection ( F  = 22.169, p <.001, R 2 =.057) to IPE, suggesting between-network validity., Conclusions: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.

Background: Gastric cancer (GC) is one of the most common tumours in East Asia countries and is associated with Helicobacter pylori infection. H. pylori utilizes virulence factors, CagA and VacA, to up-regulate pro-inflammatory cytokines and activate NF-κB signaling. Meanwhile, the PIEZO1 upregulation and cancer-associated fibroblast (CAF) enrichment were found in GC progression. However, the mechanisms of PIEZO1 upregulation and its involvement in GC progression have not been fully elucidated., Methods: The CAF enrichment and clinical significance were investigated in animal models and primary samples. The expression of NF-κB and PIEZO1 in GC was confirmed by immunohistochemistry staining, and expression correlation was analysed in multiple GC datasets. GSEA and Western blot analysis revealed the YAP1-CTGF axis regulation by PIEZO1. The stimulatory effects of CTGF on CAFs were validated by the co-culture system and animal studies. Patient-derived organoid and peritoneal dissemination models were employed to confirm the role of the PIEZO1-YAP1-CTGF cascade in GC., Results: Both CAF signature and PIEZO1 were positively correlated with H. pylori infection. PIEZO1, a mechanosensor, was confirmed as a direct downstream of NF-κB to promote the transformation from intestinal metaplasia to GC. Mechanistic studies revealed that PIEZO1 transduced the oncogenic signal from NF-κB into YAP1 signaling, a well-documented oncogenic pathway in GC progression. PIEZO1 expression was positively correlated with the YAP1 signature (CTGF, CYR61, and c-Myc, etc.) in primary samples. The secreted CTGF by cancer cells stimulated the CAF infiltration to form a stiffened collagen-enrichment microenvironment, thus activating PIEZO1 to form a positive feedback loop. Both PIEZO1 depletion by shRNA and CTGF inhibition by Procyanidin C1 enhanced the efficacy of 5-FU in suppressing the GC cell peritoneal metastasis., Conclusion: This study elucidates a novel driving PIEZO1-YAP1-CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC. H. pylori-NF-κB activates the PIEZO1-YAP1-CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1-YAP1-CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: The majority of kidney recipients are a subset of chronic kidney disease. Our previous study demonstrated that the combination of Lactobacillus plantarum and Lactobacillus paracasei (Lm) had the highest clearance ability of uremic toxins and improved kidney function in a mouse model. This study aimed to evaluate Lm in improving graft function, effects on immunosuppressants, and safety in transplant recipients., Methods: We retrospectively reviewed 24 patients. Twelve of them take Lm regularly; we compared the creatinine measurements and estimated glomerular filtration rate 3 months before and after Lm using a 2-tailed Wilcoxon matched-pairs signed-rank test while also evaluating the drug level of immunosuppressants and infection events. Other 12 patients who do not have Lm for evaluation of laboratory calibration and compared the proportion of improving creatinine using Fisher's exact test., Results: The creatinine decreased by 0.06 mg/dL (P = .02), and the estimated glomerular filtration rate increased by 3.1 mL/min/1.73 m 2 (P = .03) after Lm supplementation. This pilot study revealed the association of higher incidence (odds ratio 13.3, 95% CI 1.64-77.2, P = .01) of decreasing creatinine in transplant recipients using Lm. Furthermore, results showed a trend of higher trough levels of tacrolimus and sirolimus, which might provide a potential strategy for reducing the dosages of immunosuppressants., Conclusion: Our findings revealed an association between a higher incidence of decreasing creatinine in kidney transplant recipients using Lm, which may also provide a potential strategy for reducing the acquired dosages of immunosuppressants., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Accumulating evidence has underscored the importance of the Hippo-YAP1 signaling in lung tissue homeostasis, whereas its deregulation induces tumorigenesis. YAP1 and its paralog TAZ are the key downstream effectors tightly controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In solid tumors, Hippo-YAP1 crosstalks with other signaling pathways such as Wnt/β-catenin, receptor tyrosine kinase cascade, Notch and TGF-β to synergistically drive tumorigenesis. As YAP1/TAZ expression is significantly correlated with unfavorable outcomes for the patients, small molecules have been developed for targeting YAP1/TAZ to get a therapeutic effect. In this review, we summarize the recent findings on the deregulation of Hippo-YAP1 pathway in nonsmall cell lung carcinoma, discuss the molecular mechanisms of its dysregulation in leading to tumorigenesis, explore the therapeutic strategies for targeting YAP1/TAZ, and provide the research directions for deep investigation. We believe that detailed delineation of Hippo-YAP1 regulation in tumorigenesis provides novel insight for accurate therapeutic intervention., (© 2022 UICC.)

Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment exerts crucial effects in driving CRC progression. Cancer-associated fibroblasts (CAFs) serve as one of the most important tumor microenvironment components promoting CRC progression. This study aimed to elucidate the novel molecular mechanisms of CAF-secreted insulin-like growth factor (IGF) 2 in colorectal carcinogenesis. Our results indicated that IGF2 was a prominent factor upregulated in CAFs compared with normal fibroblasts. CAF-derived conditioned media (CM) promoted tumor growth, migration, and invasion of HCT 116 and DLD-1 cells. IGF1R expression is significantly increased in CRC, serving as a potent receptor in response to IGF2 stimulation and predicting unfavorable outcomes for CRC patients. Apart from the PI3K-AKT pathway, RNA-seq analysis revealed that the YAP1-target signature serves as a prominent downstream effector to mediate the oncogenic signaling of IGF2-IGF1R. By single-cell RNA sequencing (scRNA-seq) and immunohistochemical validation, IGF2 was found to be predominantly secreted by CAFs, whereas IGF1R was expressed mainly by cancer cells. IGF2 triggers the nuclear accumulation of YAP1 and upregulates YAP1 target signatures; however, these effects were abolished by either IGF1R knockdown or inhibition with picropodophyllin (PPP), an IGF1R inhibitor. Using CRC organoid and in vivo studies, we found that cotargeting IGF1R and YAP1 with PPP and verteporfin (VP), a YAP1 inhibitor, enhanced antitumor effects compared with PPP treatment alone. In conclusion, this study revealed a novel molecular mechanism by which CAFs promote CRC progression. The findings highlight the translational potential of the IGF2-IGF1R-YAP1 axis as a prognostic biomarker and therapeutic target for CRC. © 2022 The Pathological Society of Great Britain and Ireland., (© 2022 The Pathological Society of Great Britain and Ireland.)

Descending stairs is an indicator of independence among stroke survivors, but is demanding in terms of both neuromuscular control and cognitive functioning. Previous studies found a compromised performance when stepping down with a concurrent cognitive task among healthy older adults, but whether stroke survivors react similarly is not known. This cross-sectional study thus investigated how stroke survivors responded to a dual-task that involved stepping down and compared their performance with that of control subjects. Thirty-four healthy individuals and 26 stroke survivors reacted to an auditory Stroop test while stepping off a 19-cm high platform. The auditory Stroop test was evaluated with a composite score (dividing accuracy by averaged reaction time). Stepping down performances were quantified with subjects' sway amplitudes in anteroposterior and mediolateral directions after landing and sway velocities of their center of pressure. Stroke survivors demonstrated significantly lower composite scores when dual-tasking (76.4 ± 31.2) than when single-tasking (90.0 ± 25.6), while no significant change in stepping down performance was observed. Stroke survivors also swayed significantly more and with a higher velocity than controls when dual-tasking. The results suggested that stroke survivors adopted a posture-first strategy to deal with this dual-tasking challenge. This study raised the awareness on dual-tasking ability among stroke survivors.

Lung cancer is the common and leading cause of cancer death worldwide. The tumor microenvironment has been recognized to be instrumental in tumorigenesis. To have a deep understanding of the molecular mechanism of nonsmall cell lung carcinoma (NSCLC), cancer-associated fibroblasts (CAFs) have gained increasing research interests. CAFs belong to the crucial and dominant cell population in the tumor microenvironment to support the cancer cells. The interplay and partnership between cancer cells and CAFs contribute to each stage of tumorigenesis. CAFs exhibit prominent heterogeneity and secrete different kinds of cytokines and chemokines, growth factors and extracellular matrix proteins involved in cancer cell proliferation, invasion, metastasis and chemoresistance. Many studies focused on the protumorigenic functions of CAFs, yet many challenges about the heterogeneity of CAFS remain unresolved. This review comprehensively summarized the tumor-promoting role and molecular mechanisms of CAFs in NSCLC, including their origin, phenotypic changes and heterogeneity and their functional roles in carcinogenesis. Meanwhile, we also highlighted the updated molecular classifications based on the molecular features and functional roles of CAFs. With the development of cutting-edge platforms and further investigations of CAFs, novel therapeutic strategies for accurately targeting CAFs in NSCLC may be developed based on the increased understanding of the relevant molecular mechanisms., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The Hippo pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration under physiological conditions, and its aberrations have been well studied to promote tumor initiation and progression. Dysregulation of the Hippo tumor suppressor signaling frequently occurs in gastric cancer (GC) and other solid tumors and contributes to cancer development through modulating multiple aspects, including cell proliferation, survival, metastasis, and oncotherapy resistance. In the clinic, Hippo components also possess diagnostic and prognostic values for cancer patients. Considering its crucial role in driving tumorigenesis, targeting the Hippo pathway may greatly benefit developing novel cancer therapies. This review summarizes the current research progress regarding the core components and regulation of the Hippo pathway, as well as the mechanism and functional roles of their dysregulation in gastrointestinal malignancies, especially in GC, and discusses the therapeutic potential of targeting the Hippo pathway against cancers.

Few drugs alleviate non-small cell lung cancer (NSCLC) metastasis effectively. Small molecular screening demonstrated that fangchinoline (Fan) reversed epithelial-mesenchymal transition (EMT) in NSCLC cells, inhibiting cell invasion and migration. RNA sequencing (RNA-seq) of Fan-treated NSCLC cells revealed that Fan potently quenched the NADP + metabolic process. Molecular docking analysis revealed that Fan directly and specifically targeted NOX4. NOX4 was associated with poor prognosis in NSCLC in both The Cancer Genome Atlas (TCGA) and Hong Kong cohorts. In mitochondrial DNA-depleted ρ 0 NSCLC cells, Fan decreased cytosolic reactive oxygen species (ROS) to inhibit the Akt-mTOR signaling pathway by directly promoting NOX4 degradation. In TCGA and Hong Kong cohorts, NOX4 upregulation acted as a driver event as it positively correlated with metastasis and oxidative stress. Single-cell RNA-seq indicated that NOX4 was overexpressed, especially in cancer cells, cancer stem cells, and endothelial cells. In mice, Fan significantly impeded subcutaneous xenograft formation and reduced metastatic nodule numbers in mouse lung and liver. Drug sensitivity testing demonstrated that Fan suppressed patient-derived organoid growth dose-dependently. Fan is a potent small molecule for alleviating NSCLC metastasis by directly targeting NOX4 and is a potential novel therapeutic agent., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As one of the fastest-growing additive manufacturing (AM) technologies, fused deposition modelling (FDM) shows great potential in printing natural fibre-reinforced composites (NFRC). However, several challenges, such as low mechanical properties and difficulty in printing, need to be overcome. Therefore, the effort to improve the NFRC for use in AM has been accelerating in recent years. This review attempts to summarise the current approaches of using NFRC as a feeder for AM. The effects of fibre treatments, composite preparation methods and addition of compatibilizer agents were analysed and discussed. Additionally, current methods of producing feeders from NFRCs were reviewed and discussed. Mechanical property of printed part was also dependent on the printing parameters, and thus the effects of printing temperature, layer height, infill and raster angle were discussed, and the best parameters reported by other researchers were identified. Following that, an overview of the mechanical properties of these composites as reported by various researchers was provided. Next, the use of optimisation techniques for NFRCs was discussed and analysed. Lastly, the review provided a critical discussion on the overall topic, identified all research gaps present in the use of NFRC for AM processes, and to overcome future challenges.

In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial-mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.

Technetium poses an environmental hazard because of its radioactivity and long half-life. It exists in the form of pertechnetate in the environment and can be modeled by the nonradioactive ion perrhenate, since pertechnetate and perrhenate have the same geometry and similar chemical properties. In this research, a new zinc cyclen resorcinarene cavitand (ZCR) column was used in ion chromatography (IC) to efficiently separate perrhenate. Ion chromatography has the advantage of requiring almost no sample preparation for water samples. The ZCR column demonstrated the ability to separate anions: fluoride, chloride, nitrate, sulfate, phosphate, perchlorate, and perrhenate by gradient 2-60 mM NaOH. Unlike other columns, the new column material was selective in retaining perrhenate. The ZCR column also gave a linear range from 2.0 to 1000 mg L -1 for perrhenate with R 2 > 0.997. There was a logarithmic relationship between the concentration of perrhenate and its retention time. Excellent perrhenate recovery was achieved on the ZCR column when river water was spiked with perrhenate and perrhenate was preconcentrated. The efficient separations of perrhenate by the ZCR column will potentially assist in pertechnetate separations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

Objective: To compare the effect of Tai Chi training with conventional exercise on dual-tasking performance among stroke survivors., Design: An assessor-blinded, randomized controlled trial., Subjects: Community-dwelling stroke survivors., Setting: Community centers and university., Interventions: Subjects in the Tai Chi group and the conventional exercise group were trained with the corresponding exercises for 12 weeks (1 hour/session, 2/week). No training was given to the controls., Main Measures: An auditory Stroop test, a turning-while-walking test, and a dual-tasking condition that combined the two tests were conducted at baseline, after the intervention, and one month later., Results: Forty-seven subjects were randomized into Tai Chi group ( n = 15), conventional exercise group ( n = 17), or control group ( n = 15). There was no significant difference in the outcome measures among the three groups after the intervention and at the one month follow-up assessment. Within-group comparisons showed improvements in dual-tasking performance after Tai Chi training and further improvement during the follow-up period (composite score on the auditory Stroop test: pre-assessment: 73.1 ± 27.6, post-assessment: 89.9 ± 23.4, follow-up assessment: 91.7 ± 26.9; completion time of the turning-while-walking test: pre-assessment: 17.7 ± 6.9 seconds, post-assessment: 15.6 ± 5.2 seconds, follow-up assessment: 14.9 ± 4.9 seconds)., Conclusion: Tai Chi training does not have superior effect on dual-tasking performance compared with conventional exercise among stroke survivors. Further studies with larger sample size, longer training, and follow-up periods are needed.

Background: Turning-while-walking is one of the commonest causes of falls in stroke survivors. It involves cognitive processing and may be challenging when performed concurrently with a cognitive task. Previous studies of dual-tasking involving turning-while-walking in stroke survivors show that the performance of physical tasks is compromised. However, the design of those studies did not address the response of stroke survivors under dual-tasking condition without specifying the task-preference and its effect on the performance of the cognitive task., Objective: First, to compare the performance of single-tasking and dual-tasking in stroke survivors. Second, to compare the performance of stroke survivors with non-stroke controls., Methods: Fifty-nine stroke survivors and 45 controls were assessed with an auditory Stroop test, a turning-while-walking test, and a combination of the two single tasks. The outcome of the cognitive task was measured by the reaction time and accuracy of the task. The physical task was evaluated by measuring the turning duration, number of steps to turn, and time to complete the turning-while-walking test., Results: Stroke survivors showed a significantly reduced accuracy in the auditory Stroop test when dual-tasking, but there was no change in the reaction time. Their performance in the turning-while-walking task was similar under both single-tasking and dual-tasking condition. Additionally, stroke survivors demonstrated a significantly longer reaction time and lower accuracy than the controls both when single-tasking and dual-tasking. They took longer to turn, with more steps, and needed more time to complete the turning-while-walking task in both tasking conditions., Conclusions: The results show that stroke survivors with high mobility function performed the auditory Stroop test less accurately while preserving simultaneous turning-while-walking performance. They also demonstrated poorer performance in both single-tasking and dual-tasking as compared with controls.

Descending stairs demands attention and neuromuscular control, especially with dual-tasking. Studies have demonstrated that stroke often degrades a survivor's ability to descend stairs. Tai Chi has been shown to improve dual-tasking performance of healthy older adults, but no such study has been conducted in stroke survivors. This study investigated the effect of Tai Chi training on dual-tasking performance that involved stepping down and compared it with that of conventional exercise among stroke survivors. Subjects were randomized into Tai Chi ( n = 9), conventional exercise ( n = 8), and control ( n = 9) groups. Those in the former two groups received 12-week training. Assessments included auditory Stroop test, stepping down test, and dual-tasking test involving both simultaneously. They were evaluated before training (time-1), after training (time-2), and one month after training (time-3). Tai Chi group showed significant improvement in the auditory Stroop test from time-1 to time-3 and the performance was significantly better than that of the conventional exercise group in time-3. No significant effect was found in the stepping down task or dual-tasking in the control group. These results suggest a beneficial effect of Tai Chi training on cognition among stroke survivors without compromising physical task performance in dual-tasking. The effect was better than the conventional exercise group. Nevertheless, further research with a larger sample is warranted.

This study examines facial tissue depth in adult Chinese-Americans. Using ultrasound, measurements were taken at 19 landmarks across the faces of 101 individuals aged from 18 to 87 years. Summary statistics are reported for a sample of 67 individuals of normal weight (as determined by a body mass index [BMI] of 19-25). Statistical analyses were used to assess relationships between tissue thickness, age, and BMI. Results indicate that no significant relationship exists between tissue thickness and age for males, and for only 3/19 points in females. Also, only four points showed significant relationships between tissue thickness and sex. However, significant relationships exist between BMI and tissue thickness at multiple points for both males and females. Compared to other American and Asian populations in the literature, Chinese-Americans generally had thinner facial tissue; though, this difference was not assessed statistically. Finally, data generated in this study will add to the body of knowledge concerning facial tissue depth variation in modern humans., (© 2011 American Academy of Forensic Sciences.)

The purpose of this research is to generate carboxylic acids from the biodegradable fraction of municipal solid wastes (MSW) and municipal sewage sludge (MSS) by using a thermophilic (55 degrees C), anaerobic, high-solid fermentation. With terrestrial inocula, the highest total carboxylic acid concentration achieved was 20.5 g/L, the highest conversion obtained was 69%, and the highest acetic acid selectivity was 86.4%. Marine inocula were also used to compare against terrestrial sources. Continuum particle distribution modeling (CPDM) was used to predict the final acid product concentrations and substrate conversions at a wide range of liquid residence times (LRT) and volatile solid loading rates (VSLR). "Maps" showing the product concentration and conversion for various LRT and VSLR were generated from CPDM. The predictions were compared to the experimental results. On average, the difference between the predicted and experimental values were 13% for acid concentration and 10% for conversion. CPDM "maps" show that marine inocula produce higher concentrations than terrestrial inocula.

This communication reports SARs for the first orexin-1 receptor antagonist series of 1-aryl-3-quinolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these compounds, 31 (SB-334867), has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing.

SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3, 4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3R-ol) shows anticonvulsant activity in a range of animal seizure models, with a high therapeutic index and a lack of side-effects. We have previously reported the characterisation of a novel binding site for [(3)H]-SB-204269 in rat forebrain, which has a unique profile unrelated to other known anticonvulsant sites of action. We now describe the use of a [(125)I]-labelled form of SB-217644 (trans-6-acetyl-4S-(3-iodobenzoylamino)-3,4-dihydro-2, 2-dimethyl-2H-benzo[b]pyran-3R-ol), an analogue of SB-204269, for studies on this novel binding site. In rat forebrain membranes, [(125)I]-SB-217644 shows a similar binding profile to that of [(3)H]-SB-204269, with a maximum specific binding capacity (B(max)) of 286+/-12 fmol/mg protein, but has twenty-fold higher affinity (K(d) value 1.7+/-0.1 nM). The high affinity and high specific activity of [(125)I]-SB-217644 allowed it to be used for detection and characterisation of the detergent-solubilised form of the binding site. Specific [(125)I]-SB-217644 binding to cholate-solubilised rat cerebellum showed a K(d) value of 2.7+/-0.3 nM and a B(max) value of 55+/-11 fmol/mg protein, with a 7.3+/-0.3% yield of solubilised binding sites. [(125)I]-SB-217644 was also used in whole-cell binding assays for investigation of the properties of the novel binding site in a range of cell lines. Both rat brain neuronal and glial primary cultures and several CNS-related cell lines were found to have levels of specific [(125)I]-SB-217644 binding similar to those present in rat forebrain membranes. The solubilisation of this novel binding site, and the ability to quantify and characterise it in solubilised tissues and whole cells using [(125)I]-SB217644, will allow further studies towards the ultimate identification of the molecular target of SB-204269.

SAR studies around a series of N-(tetrahydroisoquinolinyl)-2-methoxybenzamides, identified by high-throughput screening at the novel SB-204269 binding site, have provided compounds such as 13, 29-33 with high affinity and excellent anticonvulsant activity in animal models.

Optimisation of novel cis- and trans-4-(substituted-amido)benzopyran-3-ol derivatives has led to the identification of SB-220453 20 with an in vivo pre-clinical CNS profile predictive of potential antimigraine activity.

This is a prospective study to compare the effectiveness of non-mydriatic photography with that of direct ophthalmoscopy in screening for diabetic retinopathy in 153 patients attending a hospital clinic in Hong Kong. Retinal photography under physiological mydriasis and direct ophthalmoscopy of patients with dilated pupils were compared with the ophthalmologists' examination results as a reference standard. The prevalence of diabetic retinopathy in this sample population was 15%. The sensitivity of detecting diabetic retinopathy by retinal photography was higher than that of direct ophthalmoscopy (64% versus 41%; 95% confidence interval of difference, 1.2%- 44.3%). Of five patients who had serious retinopathy, retinal photography failed to detect the disease in two; direct ophthalmoscopy failed to detect the disease in all five patients. Specificities of retinal photography and direct ophthalmoscopy were 90% (95% confidence interval, 84%-96%) and 93% (95% confidence interval, 88%-97%), respectively. We conclude that retinal photography is significantly more effective than direct ophthalmoscopy in detecting diabetic retinopathy. In addition, the non-mydriatic camera is easy to use and is the preferred method of screening.

A series of N-(tetrahydroisoquinolinyl)-2-methoxybenzamides was identified by high-throughput screening at the novel SB-204269 binding site. SAR studies have provided compounds 4 and 14 with high affinity and good anticonvulsant activity in animal models.

1. SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3, 4-dihydro-2,2-dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side-effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [3H]-SB-204269 in rat forebrain membranes. 2. Specific [3H]-SB-204269 binding was saturable and analysis indicated binding to a homogenoeous population of non-interacting binding sites with a dissociation constant (KD) of 32 +/- 1 nM and a maximum binding capacity (Bmax) of 253 +/- 18 fmol mg-1 protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na+, K+, Ca2+ or Mg2+ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues. 3. Specific [3H]-SB-204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB-204269 and its enantiomer SB-204268 for the binding site. The affinities of analogues of SB-204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action. 4. None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [3H]-SB-204269 binding site. A wide range of drugs active at amino acid receptors, Na+ or K+ channels or various other receptors did not demonstrate any affinity for the binding site. 5. These studies indicate that SB-204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.

1. Earlier optimization of structure-activity relationships in a novel series of 4-(benzoylamino)-benzopyrans, led to the discovery of SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2, 2-dimethyl-2H-benzo[b]pyran-3R-ol, hemihydrate), a potent orally-active anticonvulsant in the mouse maximal electroshock seizure threshold (MEST) test. 2. Studies have now been undertaken to determine the effects of SB-204269 in a range of seizure models and tests of neurological deficits in rats. In addition, the compound has been evaluated in a series of in vitro mechanistic assays. 3. SB-204269 proved to be an orally-effective anticonvulsant agent, at doses (0.1-30 mg Kg-1) devoid of overt behavioural depressant properties, in models of both electrically (MEST and maximal electroshock (MEST)) and chemically (i.v. pentylenetetrazol (PTZ) infusion)-evoked tonic extension seizures. However, the compound did not inhibit PTZ-induced myoclonic seizures at doses up to 30 mg kg-1, p.o. 4. SB-204269 also selectively reduced focal electrographic seizure activity in an in vitro elevated K+ rat hippocampal slice model at concentrations (0.1-10 microM) that had no effect on normal synaptic activity and neuronal excitability. 5. In all of these seizure models, SB-204269 was equivalent or better than the clinically established antiepileptic drugs carbamazepine and lamotrigine, in terms of anticonvulsant potency and efficacy. 6. Unlike SB-204269, the corresponding trans 3S,4R enantiomer, SB-204268, did not produce marked anticonvulsant effects, an observation in accord with previous findings for other related pairs of trans enantiomers in the benzopyran series. 7. In the rat accelerating rotarod test, a sensitive paradigm for the detection of neurological deficits such as sedation and motor incoordination, SB-204269 was inactive even at doses as high as 200 mg kg-1, p.o. This was reflected in the excellent therapeutic index (minimum significantly effective dose in the rotarod test/ED50 in the MES test) for SB-204269 of > 31, as compared to equivalent values of only 7 and 13 for carbamazepine and lamotrigine, respectively. 8. At concentrations (> or = 10 microM) well above those required to produce anticonvulsant activity in vivo (i.e. 0.1 microM in brain), SB-204269 did not interact with many of the well known mechanistic targets for established antiepileptic drugs (e.g. Na+ channels or GABAergic neurotransmission). Subsequent studies have shown that the anticonvulsant properties of SB-204269 are likely to be mediated by a novel stereospecific binding site present in the CNS. 9. The overall efficacy profile in rodent seizure models, together with a minimal liability for inducing neurological impairment and an apparently unique mechanism of action, highlight the therapeutic potential of SB-204269 for the treatment of refractory partial and generalized tonic-clonic seizures.

Filtration surgery is the commonest operation performed for closed angle or open angle glaucoma when medical treatment or laser trabeculoplasty has failed to control the intraocular pressure. It is characterized by the formation of an artificial drainage fistula between the anterior chamber and subconjunctival space. The successful operation is evidenced by the appearance of a subconjunctival filtration bleb which in turn depends on the patency of this pathway. Despite numerous modification, the procedure trabeculectomy first described by Sugar in 1961 and later on popularized by Watson and Cairns in 1968 is the most popular filtration surgery performed nowadays. It is a safe, relatively easy operation which carries a success rate of around 76% to 84% with a small complication rate. Repeat filtration surgery, however, is often less successful, making a successful initial surgery critically important. A successful outcome of filtration surgery can be enhanced by preoperative preparation, meticulous technique with modification for individual case, and early identification and prompt treatment of the complications arisen.