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•Physically stable dasatinib-loaded PEG-b-PLC nanomicelles were prepared with an enhanced solubility.•Both blank and dasatinib-loaded polymeric micelles were non-cytotoxic towards ...ARPE-19 cells.•Dasatinib-loaded micelles significantly inhibited PVR-related cellular changes of the retinal pigment epithelium compared to the free drug, the concentration of which was limited due to its poor solubility.•There is a linear correlation between cellular uptake and the anti-proliferating effect of polymeric micelles.•Drug loading appears to be a critical parameter for cellular uptake which in turn impacts the in vitro bioactivities of polymeric micelles.
The objective of this study was to fabricate dasatinib-loaded nanoparticles and evaluate their efficacy in inhibiting cellular processes of the retinal pigment epithelium (RPE) related to proliferative vitreoretinopathy (PVR), for which there are no approved pharmacological approaches. We successfully encapsulated dasatinib, a poorly soluble multi-targeted tyrosine kinase inhibitor which has great potential for the treatment of PVR, into nanoparticles prepared from micellation of PEG-b-PCL. The size of the nanomicelles was approximately 55nm with a narrow distribution. They increased the solubility of dasatinib by 475× and provided a sustained drug release. ARPE-19, an immortal RPE cell line, was used to assess the in vitro efficacy of micellar dasatinib because the RPE is believed to play a key role in the pathogenesis of PVR. Three cell-based assays, namely, proliferation, adhesion and migration, which represent three important PVR-related cellular changes of the RPE, were conducted and the cytotoxicity of micelles was also evaluated. Both blank and dasatinib-loaded micelles were non-cytotoxic towards ARPE-19 cells. Micellar dasatinib significantly inhibited cell proliferation, adhesion and migration compared to the free drug; this might be attributable to enhanced solubility. PEG-b-PCL micelles were taken up into the ARPE-19 cells by an energy-dependent clatharin and caveolae-mediated endocytosis. Our results indicated that cellular uptake and the anti-proliferation effect of drugloaded micelles were linearly correlated. Drug loading appears to be a critical parameter for cellular uptake which in turn impacts the in vitro bioactivities of polymeric micelles. Our results clearly demonstrated that dasatinib-encapsulated micelles offer considerable promise in the management of PVR.
In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients ...with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters.
This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome.
To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed.
Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.
Previous work on the subclones within Escherichia coli ST131 predominantly involved isolates from Western countries. This study assessed the prevalence and antimicrobial resistance attributed to this ...clonal group. A total of 340 consecutive, non-duplicated urinary E. coli isolates originating from four clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among the total isolates was 18.5 % (63/340) and was higher among inpatient isolates (23.0 %) than outpatient isolates (11.8 %, P<0.001), and higher among isolates from patients aged ≥65 years than from patients aged 18-50 years and 51-64 years (25.4 vs 3.4 and 4.0 %, respectively, P<0.001). Of the 63 ST131 isolates, 43 (68.3 %) isolates belonged to the H30 subclone, whereas the remaining isolates belonged to H41 (n = 17), H54 (n = 2) and H22 (n = 1). All H30 isolates were ciprofloxacin-resistant, of which 18.6 % (8/43) belonged to the H30-Rx subclone. Twenty-six (41.3 %) ST131 isolates were ESBL-producers, of which 19 had blaCTX-M-14 (12 non-H30-Rx, two H30-Rx and five H41), six had blaCTX-M-15 (five non-H30-Rx and one H30-Rx) and one was blaCTX-M-negative (H30). In conclusion, ST131 accounts for a large share of the antimicrobial-resistant E. coli isolates from geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly belonged to non-H30-Rx rather than the H30-Rx subclone, with blaCTX-M-14 as the dominant enzyme type.
Background: Cryoablation (CRYO) is an alternative to radiofrequency (RF) ablation in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT). This study aims to evaluate the differences ...in patient pain perception and operator stress between CRYO and RF ablation in the treatment of AVNRT.
Methods: Patients with supraventricular tachycardia underwent electrophysiology study. Twenty patients (eight males, age 46.5 ± 12.5 years) diagnosed with AVNRT were randomized to receive CRYO (11) with a 6‐mm‐tip catheter or RF (nine) with a 4‐mm‐tip catheter. Patients’ pain perception and operator stress were assessed with a visual analogue scale (VAS) from 0 to 10 at the end of procedure.
Results: There was no significant difference in acute procedural success (CRYO 100% vs RF 89%, P = 0.257). There was no complication of permanent atrioventricular block in either group. The number of energy applications was significantly higher in the CRYO group (2.8 ± 1.2 vs 1.6 ± 0.9, P = 0.02). The fluoroscopic time was significantly reduced in the CRYO group (6.0 ± 4.9 vs 10.9 ± 5.4 minutes, P = 0.049) with no difference in procedure time (CRYO 49.3 ± 12.5 vs RF 54.5 ± 17.0 minutes, P = 0.462). Patients in the CRYO group experienced significantly less pain than patients in the RF group (VAS 2.3 ± 2.8 vs 5.4 ± 3.4, P = 0.024). The operator also experienced significantly less stress during CRYO than RF (VAS 1.9 ± 0.8 vs 6.2 ± 1.6, P < 0.001). There was no recurrence in both groups at 6‐month follow‐up.
Conclusions: CRYO, as compared with RF, produces less pain in patients and less stress in operator in the treatment of AVNRT. (PACE 2011; 2–7)
Background Long-term right ventricular apical (RVA) pacing causes adverse left ventricular (LV) remodelling and clinical outcomes. Methods Forty-one patients (19 men, mean age 70.9 ± 14.2, 23 right ...ventricular septal and 18 RVA pacing) underwent pacemaker implantation for atrioventricular block. LV volumes and left ventricular ejection fraction (LVEF) were assessed by echocardiography 39.3 ± 17.2 months after implantation. Predictors of left ventricular systolic volume (LVESV), left ventricular diastolic volume (LVEDV) and LVEF were analysed. Results No difference was found between RVA pacing and right ventricular septal pacing groups in LVESV (40.6 ± 22.6 vs 33 ± 14.4 ml; p = 0.199), LVEDV (88.2 ± 31.2 vs 73.7 ± 23.9 ml; p = 0.102) and LVEF (56.1 ± 8.6 vs 56 ± 6.6%; p = 0.996). With multivariate stepwise regression, only pQRSd and renal impairment independently predicted LVESV ( β = 0.522, 95% CI: 0.242–0.802; p = 0.001 and β = 40.3, 95% CI: 17.6–62.9; p = 0.001 respectively), LVEDV ( β = 0.786, 95% CI: 0.338–1.235; p = 0.001 and β = 42.8, 95% CI: 6.6–79; p = 0.022 respectively) and LVEF ( β = −0.161, 95% CI: −0.283 to −0.04; p = 0.011 and β = −14.8, 95% CI: −24.6 to −5.0; p = 0.004 respectively). Conclusions pQRSd and renal impairment, but not pacing site or baseline LVEF, may be predictors for LV volumes and systolic function after long-term RV pacing. pQRSd may be target for pacing site optimisation.
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in a wide variety of epithelial cells, mutations of which are responsible for the hallmark ...defective chloride secretion observed in cystic fibrosis (CF). Although CFTR has been implicated in bicarbonate secretion, its ability to directly mediate bicarbonate secretion of any physiological significance has not been shown. We demonstrate here that endometrial epithelial cells possess a CFTR-mediated bicarbonate transport mechanism. Co-culture of sperm with endometrial cells treated with antisense oligonucleotide against CFTR, or with bicarbonate secretion-defective CF epithelial cells, resulted in lower sperm capacitation and egg-fertilizing ability. These results are consistent with a critical role of CFTR in controlling uterine bicarbonate secretion and the fertilizing capacity of sperm, providing a link between defective CFTR and lower female fertility in CF.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose
Catheter cryoablation (CRYO) may eliminate inadvertent atrioventricular block (AVB) in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT). However, higher recurrence was ...observed with CRYO delivered by 4 mm or 6 mm-tip catheter. This study was performed to investigate whether a comparably low treatment failure and recurrence rate as in radiofrequency (RF) ablation is achievable by CRYO with an 8-mm-tip catheter.
Methods
This is a retrospective case–control study including 40 patients with AVNRT treated with CRYO (
n
= 20) using an 8 mm-tip catheter or RF ablation (
n
= 20) from March 2009 to March 2011. Treatment failure was defined as the composite of acute procedural failure including inadvertent permanent AVB and documented recurrence.
Results
Acute procedural success of 90% (18/20) and 95% (19/20) were achieved in CRYO and RF ablation group, respectively (
p
= 0.998), with no permanent AVB in either group. With Kaplan–Meier analysis, there was no significant difference between the treatment groups in terms of recurrence rate (5.6% 1/18 vs. 0%; log-rank test
p
= 0.304) and treatment failure (15% 3/20 vs. 5% 1/20; log-rank test
p
= 0.301). Shorter fluoroscopy time (15 ± 8.6 vs. 25.2 ± 12.1 min;
p
= 0.005) and more energy applications (median 4 2–15 vs. 2 1–8;
p
= 0.005) were observed in the CRYO group compared with RF ablation group.
Conclusions
Compared to RF ablation, CRYO with an 8-mm-tip catheter for treating AVNRT achieves a comparable acute procedural success, comparably low recurrence rate and composite endpoint of treatment failure. Shorter fluoroscopy time and more energy applications were observed in the CRYO group.
Purpose
This study aims to investigate whether the use of a novel inner lumen circular mapping catheter (IMC) can shorten the procedural duration and fluoroscopic exposure of the single transseptal ...big cryoballoon (CB) pulmonary vein isolation (PVI) procedures in patients with atrial fibrillation (AF).
Methods
This is a prospective non-randomized case–control study. Forty-two patients (28 men, mean age 55.7 ± 12.1) with drug-refractory paroxysmal or persistent AF and underwent CB PVI procedures were divided into Group A (conventional single transseptal big CB approach,
n
= 21) and Group B (IMC-facilitated approach,
n
= 21). They were compared in the co-primary endpoints: (1) procedural duration and (2) fluoroscopic exposure and secondary endpoints: (1) 6-month AF-free survival and (2) number of cryo-applications.
Results
Both the procedural duration (162 ± 26 vs. 215 ± 25 min;
p
< 0.001) and fluoroscopic exposure (44.1 ± 10.4 vs. 56.8 ± 11.7 min;
p
= 0.001) were significantly shorter in Group B than Group A patients. With multivariate stepwise regression, only the use of IMC was an independent predictor for procedural duration (
β
= −59; 95 % CI, −84.1 to −33.8;
p
< 0.001) and fluoroscopic exposure (
β
= −16.9; 95 % CI, −28.4 to −5.4;
p
= 0.006). The number of cryo-applications was significantly fewer in Group B than Group A patients (median 8 vs. 11;
p
= 0.001). There was no significant difference in the 6-month AF-free survival between the two approaches (57 % vs. 71 %;
p
= 0.351).
Conclusions
Compared to conventional single transseptal big CB PVI procedures, the use of IMC may reduce procedural duration, fluoroscopic exposure and the number of cryo-applications with comparable mid-term efficacy.
OBJECTIVES:The aim of this study was to determine the pattern of dog bites seen at the emergency department of a university hospital. The information will be used to plan prevention and enhance ...management strategies.
METHODS:All patients (younger than 22 years) assessed at the emergency department between January 2003 and December 2004 with a discharge diagnosis of animal bites were identified through the computerized discharge network.
RESULTS:One hundred forty-four incidents of animal bites (82 males and 62 females) occurred over the 2-year period. Eighty-nine percent was due to dog bites. Among the dog bite victims, the mean age was 11.82 years (SD, 6.39 years; range, 0.06-21.83 years). Family dogs were only involved in 15% of cases. The species of dogs were not recognized in three fifths, and attacks provoked in two fifths of victims. Most bites (90%) of bites involved only single anatomical sites. The extremities were commonly involved (right upper limb 23%, left upper limb 16%, right lower limb 35%, left lower limb 20%). Torso (4%) and genitalia (0.8%) were uncommonly involved. Pain, erythema, bleeding, and bruising were common symptoms, but 60 patients were asymptomatic at presentation. Compared with older patients, children younger than 10 years had a much higher risk of facial injuries (25% vs. 2%, P = 0.0002; odds ratio, 21.8, 95% confidence interval, 2.9-455.9) and were more likely to be triaged as being urgent (P = 0.01). Most attacks were trivial and did not require hospitalization. Antirabies treatment was given in approximately half, analgesics in two fifths, and antibiotics in one fourth.
CONCLUSIONS:In mammalian attacks, canines are most commonly involved. Most injuries are trivial, and the limbs are usually involved. However, younger children are at higher risk of facial injuries. Extent of pain and adverse psychological impacts are typically not documented in the emergency assessment.
Background Cardiac resynchronization therapy （CRT） is an effective electrical therapy for patients with moderate to severe heart failure and cardiac dyssynchrony. This study aimed to investigate the ...degree of acute left ventricular （LV） resynchronization with biventricular pacing （BVP） at different LV sites and to examine the feasibility of performing transthoracic echocardiography （TTE） to quantify acute LV resynchronization during CRT procedure. Methods Fourteen patients with NYHA Class Ⅲ-Ⅳ heart failure, LV ejection fraction 〈35%, QRS duration 〉120 ms and septal-lateral delay （SLD） 〉60 ms on tissue Doppler imaging （TDI）, underwent CRT implant. TDI was obtained from three apical views during BVP at each accessible LV site and SLD during BVP was derived. Synchronicity gain index （Sg） by SLD was defined as （I＋（SLD at baseline - SLD at BVP）/SLD at baseline）. Results Seventy-two sites were studied. Positive resynchronization （R＋, Sg〉1） was found in 42 （58%） sites. R＋ was more likely in posterior or lateral than anterior LV sites （66% vs. 36%, P 〈0.001）. Concordance of empirical LV lead implantation sites and sites with R＋ was 50% （7/14）. Conclusions The degree of acute LV resynchronizaUon by BVP depends on LV lead location and empirical implantation of LV lead results in only 50% concordance with R＋. Performing l-rE during CRT implantation is feasible to identify LV sites with positive resynchronization.
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