Victor Chia-Hsiang Lin

Center of mass and base of support interaction during gait

During gait the body is in a continuous state of imbalance, with each subsequent step preventing a fall. Gait balance is maintained by regulating the interactions between the center of mass (CoM) and base of support (BoS). The purpose of this study was to investigate the interaction of the CoM position and velocity (CoMv) in relation to the dynamically changing BoS throughout gait. This was quantified using: (1) The shortest distance from the CoM to the boundary of the BoS; (2) The distance from the CoM to the centroid of the BoS; and (3) The distance from the CoM to the BoS along the direction of the CoMv. These interactions were investigated in healthy young adults, healthy older adults, and elderly fallers, who performed level walking at a self-selected speed. Elderly fallers demonstrated a conservative CoM-BoS separation at toe off and reduced balance control ability, specifically a decreased time to contact, when compared to healthy young adults at heel strike. Decreased time available in responding to perturbations might result in a greater number of falls. Understanding foot position and CoM trajectories might allow for appropriate rehabilitation practices.

Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors

The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range 10 kPa-30 kPa, near those of the healthy tissue. On stiffer substrates (>60 kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (<1 kPa) PAA gels myocytes exhibit disorganized actin networks and sarcomeres. However, when the polyacrylamide matrix is replaced by hyaluronic acid (HA) as the gel network to which integrin ligands are attached, robust development of functional neonatal rat ventricular myocytes occurs on gels with elastic moduli of 200 Pa, a stiffness far below that of the neonatal heart and on which myocytes would be amorphous and dysfunctional when cultured on polyacrylamide-based gels. The HA matrix by itself is not adhesive for myocytes, and the myocyte phenotype depends on the type of integrin ligand that is incorporated within the HA gel, with fibronectin, gelatin, or fibrinogen being more effective than collagen I. These results show that HA alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter the response of cells that bind the ECM through integrins. The integration of HA with integrin-specific ECM signaling proteins provides a rationale for engineering a new class of soft hybrid hydrogels that can be used in therapeutic strategies to reverse the remodeling of the injured myocardium.

In Vitro and in Vivo Melanogenesis Inhibition by Biochanin A from Trifolium pratense

Our previous study showed that a methanol extract from Trifolium pratense exerted potent inhibitory activity on melanogenesis in mouse B16 melanoma cells. In the present study, the active compound in this Chinese herb extract was isolated and identified as biochanin A by mass spectrum, 1H-NMR, and 13C-NMR analysis. The inhibitory effects of biochanin A on melanogenesis were investigated in vitro in cultured melanoma cells and in vivo in zebrafish and mice. Biochanin A dose-dependently inhibited both melanogenesis and cellular tyrosinase activity in B16 cells and in zebrafish embryos. Application of a cream containing 2% biochanin A twice daily to the skin of mice also increased the skin-whitening index value after 1 week of treatment, and the increase continued for another 2 weeks. Biochanin A was confirmed as a good candidate for use as a skin-whitening agent in the treatment of skin hyperpigmentation disorders.

Genetic variants in microRNAs and microRNA target sites predict biochemical recurrence after radical prostatectomy in localized prostate cancer

Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ‐confined prostate cancer who had a median follow‐up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single‐nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan–Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16–2.21, p for trend = 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15–2.08, p for trend = 0.004) and in combined analysis (HR 1.57, 95% CI 1.26–1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and microRNA target sites can be predictive biomarkers for BCR after RP.

Individual and cumulative association of prostate cancer susceptibility variants with clinicopathologic characteristics of the disease.

BACKGROUND Recent genome-wide association studies have identified several independent single nucleotide polymorphisms (SNPs) strongly associated with prostate cancer (PCa) risk. However, their individual and cumulative associations with clinicopathologic characteristics of the disease remain inconclusive. METHODS We systematically evaluated 20 PCa risk SNPs in a cohort of 320 localized PCa patients receiving radical prostatectomy, and the associations of these variants with age at diagnosis, preoperative prostate-specific antigen concentration, Gleason score, pathologic stage, surgical margin, and lymph node metastasis were evaluated. RESULTS Eight SNPs, rs10486567 at 7p15, rs6465657 at 7q21, rs6983267, rs1447295, and rs4242382 at 8q24, 10993994 at 10q11, rs4430796 at 17q12, and rs266849 at 19q13, were significantly (P< or =0.048) associated with some specific clinicopathologic features. In combination of these 8 SNPs, men who carried 4 or 5, or more than 5 unfavorable alleles had an increasing likelihood of adverse clinicopathologic features, as compared with men who carried fewer than 4 unfavorable alleles (P for trend, 0.031, <0.001, 0.006, and 0.003, for Gleason scores 8-10, advanced pathologic stage, positive surgical margin, and lymph node metastasis, respectively). CONCLUSIONS Our results suggested that loci associated with PCa risk might also have a cumulative and significant association with disease aggressiveness.

Therapeutic effect of α-blockers and antimuscarinics in male lower urinary tract symptoms based on the International Prostate Symptom Score subscore ratio

Aims:  To investigate if the International Prostate Symptom Score (IPSS) voiding‐to‐storage subscore ratio (IPSS‐V/S) can help to guide the treatment for male lower urinary tract symptoms (LUTS).

The effect of pre-emptive use of minimal dose fentanyl on fentanyl-induced coughing.

We performed a randomised, double‐blind study to evaluate the effect of the pre‐emptive use of minimal dose intravenous fentanyl (25 μg) on the incidence of cough caused by a larger bolus of intravenous fentanyl. Six hundred patients were randomly assigned to one of three groups to receive either 0.5 ml saline 0.9% 1 min before administration of fentanyl 150 μg (3 ml), or pre‐emptive fentanyl 25 μg (0.5 ml) 1 min before administration of fentanyl 125 μg or 150 μg. The incidence of fentanyl‐induced cough was significantly lower in both pre‐emptive groups (7 (3.5%) for 125 μg fentanyl and 15 (7.5%) for 150 μg fentanyl) than in the saline group (37 (18.5%); p = 0.001). We conclude that pre‐emptive use of fentanyl 25 μg, administered 1 min before bolus injection of fentanyl (125 or 150 μg), can effectively suppress fentanyl‐induced cough.

Genetic variants of the autophagy pathway as prognostic indicators for prostate cancer

Autophagy is a complex process of autodigestion in conditions of cellular stress, and it might play an important role in the pathophysiology during carcinogenesis. We hypothesize that genetic variants of the autophagy pathway may influence clinical outcomes in prostate cancer patients. We genotyped 40 tagging single-nucleotide polymorphisms (SNPs) from 7 core autophagy pathway genes in 458 localized prostate cancer patients. Multivariate Cox regression was performed to evaluate the independent association of each SNP with disease progression. Positive findings were then replicated in an independent cohort of 504 advanced prostate cancer patients. After adjusting for known clinicopathologic factors, the association between ATG16L1 rs78835907 and recurrence in localized disease [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.54–0.90, P = 0.006] was replicated in more advanced disease (HR 0.78, 95% CI 0.64–0.95, P = 0.014). Additional integrated in silico analysis suggests that rs78835907 tends to affect ATG16L1 expression, which in turn is correlated with tumor aggressiveness and patient prognosis. In conclusion, genetic variants of the autophagy pathway contribute to the variable outcomes in prostate cancer, and discovery of these novel biomarkers might help stratify patients according to their risk of disease progression.

Genetic variants in nuclear factor-kappa B binding sites are associated with clinical outcomes in prostate cancer patients

Nuclear factor-kappa B (NF-κB) transcription factors have been suggested to be involved in prostate cancer progression. Activated NF-κB translocates to the nucleus, binds to NF-κB binding sites and regulates target gene expression, leading to the given physiological response. It was hypothesised that the sequence variants in NF-κB binding sites might affect prostate cancer progression. We systematically evaluated 15 single-nucleotide polymorphisms (SNPs) within NF-κB binding sites those were predicted using a genome-wide database in a cohort of 1024 prostate cancer patients. Associations of these SNPs with prostate cancer characteristics and clinical outcomes after radical prostatectomy (RP) for localised disease, and after androgen-deprivation therapy (ADT) for advanced disease were assessed by Kaplan-Meier analysis and Cox regression model. We found that PSMD7 rs2387084 and MYCN rs1429409 were significantly related to earlier onset of prostate cancer and advanced clinical stage, respectively. No SNPs were significantly associated with disease recurrence after RP. Four and three SNPs were notably associated with prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM), respectively, after ADT. LSAMP rs13088089, CCL17 rs223899, PSMD7 rs2387084 and MON1B rs284924 remained the significant predictors for PCSM whilst PSMD7 rs2387084 remained a significant predictor for ACM in multivariate models including clinical predictors. Moreover, we also noted that there were strong effects of the combined genotype on PCSM and patients with a greater number of unfavourable genotypes had a shorter time to PCSM during ADT (P for trend<0.001). It was concluded that SNPs inside NF-κB binding sites might be useful to improve outcome prediction in prostate cancer patients.

Effects of early pelvic-floor muscle exercise for sexual dysfunction in radical prostatectomy recipients.

Background: Sexual dysfunction is common after radical prostatectomy (RP). Although pelvic-floor muscle exercise (PFME) has been recommended for sexual dysfunction, the optimal time for starting exercises after this surgery and the effects of exercise still need to be examined. Objectives: The present study was intended to explore the prevalence of sexual dysfunction and to assess the efficacy of PFME in sexual dysfunction following RP. Methods: Participants were randomly distributed into an experimental group (n = 35) or a control group (n = 27). The experimental group took part in PFME as part of regular daily activities after catheter removal post-RP. The control group was taught the exercise in the third month after RP. We followed up the participants at 1, 3, 6, 9, and 12 months. Results: All of the patients experienced a severe degree of sexual dysfunction after receiving RP. A t test showed a significant difference in the sexual function mean score between the experimental and control groups at 6 and 12 months. A mixed-model analysis indicated that, after a controlled surgical approach, there was a significant difference in group effect. The experimental group’s sexual function was better than the control group’s sexual function. Conclusion: This study demonstrates that early PFME is an effective intervention for sexual dysfunction in prostatectomy patients. The results can help healthcare providers to include this intervention in patients’ discharge plans. Implications for Practice: Patient sexual dysfunction after an RP is common. Nurses should evaluate and manage patients’ sexual dysfunction and promote the early return of patients’ potency.