Light- and Redox-Responsive Block Copolymers of mPEG-SS-ONBMA as a Smart Drug Delivery Carrier for Cancer Therapy.

The development of stimuli-responsive polymeric micelles for targeted drug delivery has attracted much research interest in improving therapeutic outcomes. This study designs copolymers responsive to ultraviolet (UV) light and glutathione (GSH). A disulfide linkage is positioned between a hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) and a hydrophobic o-nitrobenzyl methacrylate (ONBMA) to yield amphiphilic copolymers termed mPEG-SS-pONBMA. Three copolymers with different ONBMA lengths are synthesized and formulated into micelles. An increase in particle size and a decrease in critical micelle concentration go together with increasing ONBMA lengths. The ONB cleavage from mPEG-SS-pONBMA-formed micelles results in the transformation of hydrophobic cores into hydrophilic ones, accelerating drug release from the micelles. Obvious changes in morphology and molecular weight of micelles upon combinational treatments account for the dual-stimuli responsive property. Enhancement of a cell-killing effect is clearly observed in doxorubicin (DOX)-loaded micelles containing disulfide bonds compared with those containing dicarbon bonds upon UV light irradiation. Collectedly, the dual-stimuli-responsive mPEG-SS-pONBMA micelle is a better drug delivery carrier than the single-stimuli-responsive mPEG-CC-pONBMA micelle. After HT1080 cells were treated with the DOX-loaded micelles, the high expression levels of RIP-1 and MLKL indicate that the mechanism involved in cell death is mainly via the DOX-induced necroptosis pathway.

Effect of Age on Heart Rate Variability in Patients with Mitral Valve Prolapse: An Observational Study.

Age is an important determinant of heart rate variability (HRV) in healthy individuals. The incidence of arrhythmia is high in patients with mitral valve prolapse (MVP). However, the correlation of HRV in patients with MVP in different age groups is not well established. We presumed that increasing age would be prospectively associated with declining HRV measurement in MVP. Sixty patients with MVP and 120 control individuals were included and underwent 24 h HRV analysis. No significant difference was found in all parameters calculated in the time domain or in the frequency domain between the two groups. However, as patients' age increased, a significant time domain (SDNN, RMSSD, NN50, and pNN50) decline was found in the MVP group, but not in the control group. This suggests that patients with MVP may have autonomic nervous system involvement that increases the risk of arrhythmia and heart disease with increasing age.

A Versatile Kit Based on Digital Microfluidics Droplet Actuation for Science Education.

This paper describes an educational kit based on digital microfluidics. A protocol for luminol-based chemiluminescence experiment is reported as a specific example. It also has fluorescent imaging capability and closed humidified enclosure based on an ultrasonic atomizer to prevent evaporation. The kit can be assembled within a short period of time and with minimal training in electronics and soldering. The kit allows both undergraduate/graduate students and enthusiasts to obtain hands-on experience in microfluidics in an intuitive way and be trained to gain familiarity with digital microfluidics.

Comparison of Chest Compression Quality between Transfer Sheet and Stretcher Use for Transporting out-of-Hospital Cardiac Arrest Patients in a High-Rise Building - A Randomized and Open-Label Cross-over Design.

OBJECTIVES: Stretchers are commonly used for transporting cardiac arrest patients, but their use may be limited in confined spaces, like elevators. Use of transfer sheet as an alternative has not been explored. We aimed to compare manual chest compression quality between these two methods. Methods: In this prospective, open-label, randomized cross-over manikin study, the subjects included emergency medical technicians who were assigned to 12 three-person crews. Scenarios included transport of a cardiac arrest in a high-rise building and elevator using transfer sheet (TS) and stretchers adjusted to 45° (S45) and 90° (S90). Chest compression quality was measured using a recording manikin and that before (on-scene phase) and after (transport phase) the manikin moved via transfer sheet or stretcher were compared. Results: The final analysis included 72 simulation runs. Chest compression quality did not differ among the groups in the on-scene phase. In the transport phase, the transfer sheet group provided greater mean compression depth (54.4 ± 4.2 vs 39.6 ± 7.2 mm, p < 0.01 and 54.4 ± 4.2 vs 40.6 ± 8.3 mm, p < 0.01, respectively) than stretchers of S45 and S90, and higher percentage of deep-enough compression (TS: 51.0 [23.8-74.8]% vs S45: 19.5 [5.8-29.5]%, p < 0.01) than the S45 group. Transfer sheet use showed a trend of lower percentages of full recoil (TS: 40.0 [12.8-64.5]% vs S45: 70.5 [47.0-79.8]% vs S90: 52.5 [25.3-76.0]%, p = 0.09). Chest compression fraction, compressions with correct hand position, and mean compression rates did not differ between groups in the transport phase. The TS group showed shorter time intervals of simulation start-to-first-compression (TS: 13.9 [12.4-15.1] sec vs S90: 15.9 [13.3-16.4] sec, p = 0.04) and total run time (TS: 145.7 [135.1-151.4] sec vs S90: 160.0 [151.9-175.4] sec, p < 0.01) than the S90 group. Conclusion: In this simulation, using transfer sheet outperform using stretcher for transporting cardiac arrest patients from high-rise buildings. Rescuers need to be aware of full chest recoil.

Wireless bioreactor for anaerobic cultivation of bacteria.

Anaerobic cultivation methods of bacteria are indispensable in microbiology. One methodology is to cultivate the microbes in anaerobic enclosure with oxygen-adosrbing chemicals. Here, we report an electronic extension of such strategy for facultative anaerobic bacteria. The technique is based a bioreactor with entire operation including turbidity measurement, fluidic mixing, and gas delivery in an anaerobic enclosure. Wireless data transmission is employed and the anaerobic condition is achieved with gas pack. Although the technique is not meant to completely replace the anaerobic chamber for strict anaerobic bacteria, it provides a convenient way to bypass the cumbersome operation in anaerobic chamber for facultative anaerobic bacteria. Such a cultivation strategy is demonstrated with Escherichia coli with different carbon sources and hydrogen as energy source.

Experiences and Psychological Influences in Lay Rescuers Performing Bystander Cardiopulmonary Resuscitation: A Qualitative Study.

BACKGROUND: Bystander-initiated cardiopulmonary resuscitation (CPR) and the use of automated external defibrillation (AED) is pivotal in the community chain of survival, but little is known regarding the bystander experience of performing CPR and AED, and their psychological infl uence from the incidents in the Asian community. This qualitative study was conducted to explore the experiences of lay rescuers who had performed CPR and AED in public locations in Taiwan. METHODS: Lay rescuers who had provided initial CPR and defi brillation with AED in public locations across Taiwan in 2015 were selectively recruited from Taiwan Public AED Registry for a semi-structured interview. RESULTS: Nine participants were included in the study, and event-to-interview duration was within 1 year (n = 4) and 1-2 years (n = 5). The major fi ndings from the study were: (1) the lay rescuers possessed helping traits and high motivation; (2) the lay rescuers reported certain aspects of rescue reality that differed much from prior training and expectations, including diffi culty in the depth of chest compression, and uncertainties in real emergency situations; (3) the lay rescuers gained positive personal fulfi llment in sharing their experience and receiving positive feedback from others, and were willing to help next time, although they experienced a short-term negative psychological impact from the event. CONCLUSIONS: This study provides valuable information on strategies to increase layperson CPR rates and effectiveness in CPR training. Measures should be taken to increase layperson's confi dence and situation awareness, reduce training-reality discrepancy, build up a support system to avoid negative psychological effects, and prepare lay rescuers for the next resuscitation.

Use of a Perclose ProGlide device for percutaneous endovascular aortic aneurysm repair in a general hospital experience.

BACKGROUND: This study evaluated the safety and efficacy of percutaneous endovascular aortic aneurysm repair (EVAR) with a Perclose ProGlide device compared with endovascular aortic repair with surgical cutdown of common femoral artery in patients at a general hospital. METHODS: A retrospective clinical study was conducted using data on 10 patients with elective EVAR, 7 patients with percutaneous EVAR, and 9 patients with consecutive rupture abdominal aortic aneurysm treated with emergency EVAR from January 2010 to December 2014. RESULTS: The median length of intensive care unit stay for elective EVAR, percutaneous EVAR, and emergency EVAR cases: 1.80±0.92 days, 1.67±1.21 days, and 10.00±13.27 days, respectively; hospital days: 11.10±4.28 days, 11.00±4.10 days, and 21.89±18.35 days, respectively. Seven patients have no calcification in common femoral artery, and the use of a Perclose ProGlide device was under the guidance of sonography for percutaneous EVAR. The operative times of elective EVAR, percutaneous EVAR, and emergency EVAR were 192.3±52.0 minutes, 169.2±67.5 minutes, and 227.1±59.9 minutes, and blood loss volumes were 150.0±77.5 ml, 95.0±78.6 ml, and 422.2±276.3 ml, respectively. Technical success rate of Perclose ProGlide was 100%. CONCLUSIONS: Selective percutaneous access of the femoral arteries for EVAR is safe and effective in the studied cases. The complications can be avoided with careful selection of patients based on preoperative imaging. Using Perclose ProGlide for select cases may reduce blood loss and operative time.

Clinical outcomes of infrarenal abdominal aortic aneurysms that underwent endovascular repair in a district general hospital.

BACKGROUND: The purpose of this study was to compare the outcomes of elective endovascular abdominal aortic aneurysm repair (EVAR) and ruptured abdominal aortic aneurysm (rAAA) in patients at a district general hospital. METHODS: A retrospective clinical study was conducted using data on 16 patients with elective abdominal aortic aneurysm (AAA) and nine patients with consecutive rAAA treated with EVAR from January 2010 to December 2014 in a district general hospital in Taiwan. RESULTS: The preoperative characteristics of the two groups are listed. Thirty-six percent (9/25) of the patients were referred from other hospitals that did not offer surgical services. The percentage of patients with rAAA that were transferred from other hospitals was 55.5% (5/9). The stay durations in the intensive care unit for elective EVAR cases were shorter than those for emergent EVAR (1.75±1 d elective vs. 10±13.37 d emergent; P<0.019). The hospitalization days (11.06±4.07 d elective vs. 21.89±18.36 d emergent; P<0.031), operative time (183.63±57.24 min elective vs. 227.11±59.92 min emergent; P<0.009), and blood loss volumes (115.63±80.41 mL elective vs. 422.22±276.26 mL emergent; P<0.005) are shown; statistics for use of Perclose ProGlide(®) (7 cases elective vs. 0 case emergent; P<0.024) are compared. The overall 30-d mortality rate was 11.11% (1/9). CONCLUSIONS: The results confirm that EVAR surgery can be safely performed in a district general hospital with an integrated health care system. Using Perclose ProGlide(®) for selected cases may reduce blood loss and operative time.

Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults.

BACKGROUND: Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. METHODS: A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148 healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or autoregressive methods were analyzed. RESULTS: The MVP group showed a decrease in time domain parameters and obtunded postural effects on frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male, sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male). CONCLUSIONS: Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects.

Experience of endovascular repair of thoracic aortic dissection after blunt trauma injury in a district general hospital.

BACKGROUND: Traumatic thoracic aortic dissection is uncommon in clinical practice; however, it is associated with high morbidity and mortality. Thoracic aortic dissection is usually caused by sudden deceleration resulting from a traffic accident or fall. Aortic injury after blunt trauma is a critical condition. This study reported the outcomes of endovascular repair of acute traumatic aortic dissection in patients at a district general hospital. METHODS: In this study, we retrospectively reviewed the clinical data of eight patients with acute traumatic aortic dissection after a blunt trauma who had undergone thoracic endovascular aortic repair (TEVAR) between January 2012 and December 2015 at a district general hospital in Taiwan. RESULTS: The median age of the patients was 49±22 years (range, 20-77 years), and 6 of the 8 (75%) patients were men. Five patients were involved in traffic accidents, and 3 patients had fallen from heights. The injury severity score (ISS) of the patients ranged from 17 to 66. In all patients, the aortic injury was located near the origin of the left subclavian artery (LSA). Four patients had seal ostium of subclavian artery, left. None of the patients developed paraplegia or lower extremity ischemia. Moreover, all patients had concomitant injuries, and no patients died postoperatively. CONCLUSIONS: Endovascular repair is a rapid and minimally invasive therapy for patients with traumatic aortic injury and is associated with favorable technical results.

Stent graft repair of iatrogenic femoral arteriovenous fistula with acute bleeding after hemodialysis catheter insertion.

An arteriovenous fistula (AVF) is an abnormal connection between an artery and a vein. Double-lumen catheters are widely used for gaining temporary access in patients requiring acute hemodialysis (HD). Several complications are associated with the insertion of these catheters, including bleeding, infection, arterial injuries, and deep venous thrombosis. An iatrogenic AVF is a rare and severe complication following catheterization for temporary HD. Here, we report the case of a patient who developed an iatrogenic AVF following catheterization for acute HD resulting in acute bleeding. A 61-year-old male experienced acute renal failure with pulmonary edema. A 12 French (Fr) dialysis catheter was inserted into the right femoral vein for emergent HD. Active pulsation bleeding was observed around the catheter at the right inguinal area after first HD. A thrill was felt at the superficial femoral artery after the repair of its anterior side. Angiography revealed iatrogenic AVF, which was successfully treated with stent graft repair.

Successful continuous-flow left ventricular assist device implantation with adjuvant tricuspid valve repair for advanced heart failure.

The prevalence of end-stage heart failure (HF) is on the increase, however, the availability of donor hearts remains limited. Left ventricular assist devices (LVADs) are increasingly being used for treating patients with end-stage HF. LVADs are not only used as a bridge to transplantation but also as a destination therapy. HeartMate II, a new-generation, continuous-flow LVAD (cf-LVAD), is currently an established treatment option for patients with HF. Technological progress and increasing implantation of cf-LVADs have significantly improved survival in patients with end-stage HF. Here we report a case of a patient with end-stage HF who was successfully supported using cf-LVAD implantation with adjuvant tricuspid valve repair in a general district hospital.

New vascular ring connectors in surgery for intramural haematoma of the abdominal aorta progressing to rupture.

Aortic intramural haematoma is similar to classic aortic dissection, which causes a life-threatening medical condition, and immediate diagnosis and treatment are crucial. The optimal therapy for intramural haematoma of the abdominal aorta remains controversial. Conservative medical management is usually the first choice of treatment for uncomplicated cases. Surgical intervention is usually required for complicated intramural haematomas of the abdominal aorta, including conventional open repair and endovascular treatment with stent-grafts. A new vascular ring connector that achieves a quick, blood-sealed and sutureless anastomosis has been designed for aortic dissection. We herein report a case of intramural haematoma of the abdominal aorta, progressing to rupture on day 14 after onset, which had successful aortic repair with the new vascular ring connector. The new vascular ring connector could be an alternative method for the treatment of complicated intramural haematomas of the abdominal aorta.

Localised bullous eruptions after extravasation of normal saline in the forearm during left ventricular device-assisted surgery.

Peripheral infusion of intravenous agents is a daily routine in hospitals. Extravasation is an unintended complication associated with intravenous infusion where accidental injection or leakage of fluid occurs into the perivascular or subcutaneous space. Extravasation is fairly common but is usually without serious consequences. This has led clinicians to underestimate the potentially serious consequences of extravasation. Extravasation injury results from a combination of factors, including cytotoxicity of the solution, osmolality, vasoconstrictor effects, infusion pressure and other factors. We describe a case of upper extremity localised bullous eruptions resulting from the pressurised infusion of crystalloid solutions through an intravenous catheter, placed in the operating room during left ventricular device-assisted surgery. Peri-operative management of acute localised bullous eruptions requires surveillance for unforeseen consequences. Early recognition, diagnosis and intervention averted potential complications and morbidity.

Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms.

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). Recently, DHLA has been used as the hydrophilic nanomaterial preparations, and therefore, determination of its bio-safety profile is essential. In this article, we show that DHLA (50-100 µM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no injury effects at treatment dosages below 50 µM. Higher concentrations of DHLA (50-100 µM) directly increased the reactive oxygen species (ROS) content in ESC-B5 cells, along with a significant increase in cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with NO scavengers suppressed the apoptotic biochemical changes induced by 100 µM DHLA and promoted the gene expression levels of p53 and p21 involved in apoptotic signaling. Our results collectively indicate that DHLA at concentrations of 50-100 µM triggers apoptosis of ESC-B5 cells, which involves both ROS and NO. Importantly, at doses of less than 50 µM (0-25 µM), DHLA does not exert hazardous effects on ESC-B5 cell properties, including viability, development and differentiation. These results provide important information in terms of dosage safety and biocompatibility of DHLA to facilitate its further use as a precursor for biomaterial preparation.

Isolated lower limb ischaemia as an unusual presenting symptom of aortic dissection.

Acute aortic dissection is not common but usually presents with a severe, sharp chest pain and high blood pressure. Widening of the mediastinum is usually also evident on chest X-ray. Although acute onset of severe chest or back pain is the most common presenting symptom, some patients may present with atypical symptoms and signs. Establishing a diagnosis of aortic dissection can be difficult in the presence of atypical symptoms, especially in the absence of pain. Such presentation of aortic dissection is easily ignored. We report a case of painless aortic dissection with normal blood pressure, which resulted in acute isolated lower limb ischaemia at presentation. Atypical presentation of isolated limb arterial occlusions in an older patient without the classic symptoms are seldom reported as aortic dissection. However, aortic dissection should be included in the differential diagnosis of patients with arterial occlusive disease without chest pain and with normal blood pressure.

Fluorescent gold nanoclusters as a biocompatible marker for in vitro and in vivo tracking of endothelial cells.

We have been investigating the fluorescent property and biocompatibility of novel fluorescent gold nanoclusters (FANC) in human aortic endothelial cells (HAEC) and endothelial progenitor cells (EPC). FANC (50-1000 nmol/L) was delivered into cells via the liposome complex. The fluorescence lasted for at least 28 days with a half-life of 9 days in vitro. Examination of 12 transcripts regulating the essential function of endothelial cells after a 72 h delivery showed that only the vascular cell adhesion molecule 1 and the vascular endothelial cadherin were down-regulated at high concentration (500 nmol/L). In addition, no activation of caspase 3 or proliferating cell nuclear antigens was detected. 3-[4,5-Dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) assay demonstrated that, unlike the markedly suppressed viability in cells treated with quantum dots, FANC had minimal effect on the viability, unless above 500 nmol/L, at which level a minor reduction of viability mainly caused by liposome was found. Tube formation assay showed no impaired angiogenesis in the EPC treated with FANC. In vivo study using hindlimb ischemic mice with an intramuscular injection of FANC-labeled human EPC showed that the cells preserved an angiogenic potential and exhibited traceable signals after 21 days. These findings demonstrated that FANC is a promising biocompatible fluorescent probe.

Fabrication and characterization of multi-scale microlens arrays with anti-reflection and diffusion properties.

In this paper, an effective method for fabricating artificial compound-eye structures is demonstrated. The fabrication of high fill factor microlens arrays (MLAs) with sub-wavelength structures (SWSs) on a polycarbonate (PC) substrate involves nanoimprint and thermo-extrusion techniques by using two different scales of nano/micromolds. In addition, the MLAs with SWSs on the PC substrate would be replicated on a polymethylmethacrylate (PMMA) millimeter concave surface by hot-embossing, forming three-level compound-eye structures. The optical properties of these samples are characterized. The transmittances of two-level PC and three-level PMMA compound structures are increased by 2.5% and 2%, and the uniformities are enhanced by 18% and 24%, respectively.