Measuring Integrin Force Loading Rates Using a Two-Step DNA Tension Sensor.

Cells apply forces to extracellular matrix (ECM) ligands through transmembrane integrin receptors: an interaction which is intimately involved in cell motility, wound healing, cancer invasion and metastasis. These small (piconewton) integrin-ECM forces have been studied by molecular tension fluorescence microscopy (MTFM), which utilizes a force-induced conformational change of a probe to detect mechanical events. MTFM has revealed the force magnitude for integrin receptors in a variety of cell models including primary cells. However, force dynamics and specifically the force loading rate (LR) have important implications in receptor signaling and adhesion formation and remain poorly characterized. Here, we develop an LR probe composed of an engineered DNA structure that undergoes two mechanical transitions at distinct force thresholds: a low force threshold at 4.7 pN (hairpin unfolding) and a high force threshold at 47 pN (duplex shearing). These transitions yield distinct fluorescence signatures observed through single-molecule fluorescence microscopy in live cells. Automated analysis of tens of thousands of events from eight cells showed that the bond lifetime of integrins that engage their ligands and transmit a force >4.7 pN decays exponentially with a τ of 45.6 s. A subset of these events mature in magnitude to >47 pN with a median loading rate of 1.1 pN s-1 and primarily localize at the periphery of the cell-substrate junction. The LR probe design is modular and can be adapted to measure force ramp rates for a broad range of mechanoreceptors and cell models, thus aiding in the study of molecular mechanotransduction in living systems.

A Comparison of Postoperative Outcomes Based on Muscle versus Fasciocutaneous Flaps in Scalp Reconstruction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Scalp reconstruction in plastic and reconstructive surgery often necessitates the transfer of soft tissue flaps to restore form and function. The critical decision lies in choosing between muscle-containing (MC) and fasciocutaneous (FC) flaps for scalp reconstruction, and while both variants have their merits, flap composition remains a subject of ongoing debate. This scientific discussion aims to explore this contentious issue through a comprehensive meta-analysis, shedding light on the rationale behind the choice of these flaps and the potential impact on clinical outcomes. METHODS: A comprehensive systematic review was conducted following PRISMA-P guidelines, encompassing six prominent databases up to the year 2023. Data were collected from studies assessing outcomes of MC and FC flaps for scalp reconstruction. Quality evaluation was performed using ASPS criteria and the ROBINS-I tool. Statistical analysis included descriptive statistics, meta-analysis, sensitivity analysis, and assessment of bias using STATA software. RESULTS: The meta-analysis included 28 non-randomized studies, totaling 594 flaps (380 MC, 214 FC). MC flaps were significantly larger than FC flaps. There were no significant differences in flap loss, flap necrosis, or wound dehiscence between the two flap types. However, the incidence of venous congestion was significantly higher in FC flaps. Sensitivity analysis confirmed the robustness of results, and publication bias assessment showed no significant evidence of bias. CONCLUSIONS: While both MC and FC flaps offer viable options for scalp reconstruction, the choice should be tailored to individual patient characteristics and defect size. FC flaps may provide advantages such as shorter operative times and reduced morbidity, whereas MC flaps could be preferred for addressing larger defects. Future research should focus on prospective studies and strategies to mitigate venous congestion in FC flaps, enhancing their safety and efficacy in scalp reconstruction.

Measuring integrin force loading rates using a two-step DNA tension sensor.

Cells apply forces to extracellular matrix (ECM) ligands through transmembrane integrin receptors: an interaction which is intimately involved in cell motility, wound healing, cancer invasion and metastasis. These small (pN) forces exerted by cells have been studied by molecular tension fluorescence microscopy (MTFM), which utilizes a force-induced conformational change of a probe to detect mechanical events. MTFM has revealed the force magnitude for integrins receptors in a variety of cell models including primary cells. However, force dynamics and specifically the force loading rate (LR) have important implications in receptor signaling and adhesion formation and remain poorly characterized. Here, we develop a LR probe which is comprised of an engineered DNA structures that undergoes two mechanical transitions at distinct force thresholds: a low force threshold at 4.7 pN corresponding to hairpin unfolding and a high force threshold at 56 pN triggered through duplex shearing. These transitions yield distinct fluorescence signatures observed through single-molecule fluorescence microscopy in live-cells. Automated analysis of tens of thousands of events from 8 cells showed that the bond lifetime of integrins that engage their ligands and transmit a force >4.7 pN decays exponentially with a τ of 45.6 sec. A small subset of these events (<10%) mature in magnitude to >56pN with a median loading rate of 1.3 pNs-1 with these mechanical ramp events localizing at the periphery of the cell-substrate junction. Importantly, the LR probe design is modular and can be adapted to measure force ramp rates for a broad range of mechanoreceptors and cell models, thus aiding in the study of mechanotransduction.

An Endosomal Escape Trojan Horse Platform to Improve Cytosolic Delivery of Nucleic Acids.

Endocytosis is a major bottleneck toward cytosolic delivery of nucleic acids, as the vast majority of nucleic acid drugs remain trapped within endosomes. Current trends to overcome endosomal entrapment and subsequent degradation provide varied success; however, active delivery agents such as cell-penetrating peptides have emerged as a prominent strategy to improve cytosolic delivery. Yet, these membrane-active agents have poor selectivity for endosomal membranes, leading to toxicity. A hallmark of endosomes is their acidic environment, which aids in degradation of foreign materials. Here, we develop a pH-triggered spherical nucleic acid that provides smart antisense oligonucleotide (ASO) release upon endosomal acidification and selective membrane disruption, termed DNA EndosomaL Escape Vehicle Response (DELVR). We anchor i-Motif DNA to a nanoparticle (AuNP), where the complement strand contains both an ASO sequence and a functionalized endosomal escape peptide (EEP). By orienting the EEP toward the AuNP core, the EEP is inactive until it is released through acidification-induced i-Motif folding. In this study, we characterize a small library of i-Motif duplexes to develop a structure-switching nucleic acid sequence triggered by endosomal acidification. We evaluate antisense efficacy using HIF1a, a hypoxic indicator upregulated in many cancers, and demonstrate dose-dependent activity through RT-qPCR. We show that DELVR significantly improves ASO efficacy in vitro. Finally, we use fluorescence lifetime imaging and activity measurement to show that DELVR benefits synergistically from nuclease- and pH-driven release strategies with increased ASO endosomal escape efficiency. Overall, this study develops a modular platform that improves the cytosolic delivery of nucleic acid therapeutics and offers key insights for overcoming intracellular barriers.

Force-Triggered Self-Destructive Hydrogels.

Self-destructive polymers (SDPs) are defined as a class of smart polymers that autonomously degrade upon experiencing an external trigger, such as a chemical cue or optical excitation. Because SDPs release the materials trapped inside the network upon degradation, they have potential applications in drug delivery and analytical sensing. However, no known SDPs that respond to external mechanical forces have been reported, as it is fundamentally challenging to create mechano-sensitivity in general and especially so for force levels below those required for classical force-induced bond scission. To address this challenge, the development of force-triggered SDPs composed of DNA crosslinked hydrogels doped with nucleases is described here. Externally applied piconewton forces selectively expose enzymatic cleavage sites within the DNA crosslinks, resulting in rapid polymer self-degradation. The synthesis and the chemical and mechanical characterization of DNA crosslinked hydrogels, as well as the kinetics of force-triggered hydrolysis, are described. As a proof-of-concept, force-triggered and time-dependent rheological changes in the polymer as well as encapsulated nanoparticle release are demonstrated. Finally, that the kinetics of self-destruction are shown to be tuned as a function of nuclease concentration, incubation time, and thermodynamic stability of DNA crosslinkers.

Open-porous magnesium-based scaffolds withstand in vitro corrosion under cyclic loading: A mechanistic study.

The successful application of magnesium (Mg) alloys as biodegradable bone substitutes for critical-sized defects may be comprised by their high degradation rate resulting in a loss of mechanical integrity. This study investigates the degradation pattern of an open-porous fluoride-coated Mg-based scaffold immersed in circulating Hanks' Balanced Salt Solution (HBSS) with and without in situ cyclic compression (30 N/1 Hz). The changes in morphological and mechanical properties have been studied by combining in situ high-resolution X-ray computed tomography mechanics and digital volume correlation. Although in situ cyclic compression induced acceleration of the corrosion rate, probably due to local disruption of the coating layer where fatigue microcracks were formed, no critical failures in the overall scaffold were observed, indicating that the mechanical integrity of the Mg scaffolds was preserved. Structural changes, due to the accumulation of corrosion debris between the scaffold fibres, resulted in a significant increase (p < 0.05) in the material volume fraction from 0.52 ± 0.07 to 0.47 ± 0.03 after 14 days of corrosion. However, despite an increase in fibre material loss, the accumulated corrosion products appear to have led to an increase in Young's modulus after 14 days as well as lower third principal strain (εp3) accumulation (-91000 ± 6361 µÎµ and -60093 ± 2414 µÎµ after 2 and 14 days, respectively). Therefore, this innovative Mg scaffold design and composition provide a bone replacement, capable of sustaining mechanical loads in situ during the postoperative phase allowing new bone formation to be initially supported as the scaffold resorbs.

Robotic pyelolithotomy in a solitary pelvic kidney complicated with fulminant Clostridium difficile: a case report.

BACKGROUND: Robotic-assisted surgeries have gradually become the standard of care for many procedures, especially in the field of urology. Despite the widespread use of robotic assistance in surgeries, data on its postoperative complications are extremely limited. We detail a rare presentation of fulminant Clostridium difficile colitis requiring surgical intervention in a patient with a solitary ectopic pelvic kidney who underwent a robotic-assisted pyelolithotomy. Highlights of the most recent management recommendations for C. difficile infection are also presented. CASE PRESENTATION: A 26-year-old Caucasian woman who underwent a robot-assisted pyelolithotomy of a pelvic kidney developed tachycardia, leukocytosis, and severe diarrhea 2 days following surgery. Because of her long history of antibiotic use, her severe symptoms were concerning for C. difficile colitis. This was confirmed by a C. difficile toxin test and a computed tomography scan. She was given recommended antibiotics, but her condition progressively deteriorated. The patient developed fulminant colitis and toxic megacolon, for which she underwent an exploratory laparotomy with subtotal abdominal colectomy and ileostomy creation on the twelfth day of her hospitalization. She fully recovered and was discharged 3 weeks after her subtotal colectomy. CONCLUSION: Although robotic surgeries have been shown to have several advantages, risk of postsurgical complications remains. We present a rare case of fulminant C. difficile colitis that complicated a robotic-assisted pyelolithotomy. Active prevention, early detection, and optimization of management are essential to preventing unfavorable outcomes.

Acute Correction of Multiplanar Proximal Tibial Deformity Utilizing Fixator-Assisted Intramedullary Nailing.

Proximal tibial deformities, particularly varus deformities, are relatively common in adolescents and young adults. The etiology of these deformities is often untreated or undercorrected infantile and adolescent Blount disease. Other less common etiologies include metabolic bone disease-associated deformities, posttraumatic and iatrogenic growth disturbance, and deformity related to surgical treatment or radiation for tumors1-3. We apply the principles of fixator-assisted acute deformity correction, mostly described for use at the distal aspect of the femur, as well as the principles of anatomic reduction and fixation of proximal-third tibial fractures4 to acutely correct these complex deformities in skeletally mature individuals5-12. We perform acute correction of multiplanar proximal tibial deformity with use of fixator-assisted intramedullary nailing in order to avoid the complications and patient discomfort associated with gradual deformity correction with use of a circular external fixator. This procedure is novel in the treatment of adolescent Blount disease deformity in skeletally mature individuals and can additionally be utilized for other proximal tibial metaphyseal deformities, allowing the accurate and acute correction of all planes of deformity as well as the anatomic and mechanical axes, while avoiding the prolonged use of external fixators. Description: The patient is positioned supine on a radiolucent table. The locations of the proximal tibial osteotomy, fibular osteotomy, external fixator pin sites, and intramedullary nail insertion site are marked with use of a surgical marker and fluoroscopic imaging. Large external fixator half-pins are placed proximal and distal to the planned tibial osteotomy in both the anterior-posterior and sagittal planes, avoiding the path of the planned tibial intramedullary nail. A fibular osteotomy and then a low-energy tibial osteotomy are performed with use of multiple drill holes and an osteotome. Next, the bone deformity is fully corrected and held in the corrected alignment with the external fixators. Then, the opening drill for the intramedullary nail is introduced into the proximal aspect of the tibia over a guidewire, and blocking screws are placed in the coronal and sagittal planes of the proximal fragment next to the opening reamer. The intramedullary canal is then reamed over a ball-tipped guidewire to the desired diameter and the selected intramedullary nail is placed and secured with proximal and distal interlocking screws. Finally, the external fixators are removed. Alternatives: Alternative operative treatments include external fixation and gradual or acute deformity correction as well as fixator-assisted acute deformity correction and plate fixation13-16. Rationale: Typically, a tibial osteotomy with gradual deformity correction with use of a circular fixator is employed for the treatment of these deformities3,17. The literature shows this to be an effective technique for accurate correction of these complex proximal tibial deformities. With the advent of internal motorized lengthening nails, however, there have been increasing efforts to develop safe and accurate techniques for acutely correcting bone deformity so that these nails can be utilized to treat both angular deformities and bone-length differences simultaneously. Deformity at the proximal aspect of the tibia is often multiplanar, and complete correction of these deformities requires translation, angulation, and rotation through the osteotomy. An osteotomy performed at the proximal aspect of the tibia results in the equivalent of a proximal-third tibial fracture, which is more challenging and more demanding to fix than a diaphyseal tibial fracture because of the wide medullary canal and the strong deforming muscular forces at the proximal tibia. Fixator-assisted intramedullary nailing with blocking screws allows for the accurate correction of the mechanical and anatomic axes while avoiding external fixation. Expected Outcomes: The expected outcome is complete bone deformity correction and healing of the osteotomy site(s)2. Important Tips: Careful preoperative planning is essential to accurately correct the anatomic and mechanical axes in all planes.In cases of acute correction of severe bone deformities, consider prophylactic nerve decompression.When possible, avoid the use of a tourniquet in order to minimize tissue trauma, postoperative swelling, and the need for prophylactic fasciotomies.Obtain and hold perfect osseous alignment with use of temporary uniplanar external fixators prior to placing any definitive hardware. Acronyms and Abbreviations: AP = anteroposteriorIM = intramedullaryPACS = picture archiving and communication systemK-wire = Kirschner wireCORA = center of rotation and angulationDVT = deep venous thrombosisPE = pulmonary embolism.

Gender Differences in Cardiac Chronotropic Control: Implications for Heart Rate Variability Research.

There is a continuing debate concerning "adjustments" to heart period variability [i.e., heart rate variability (HRV)] for the heart period [i.e., increases inter-beat-intervals (IBI)]. To date, such arguments have not seriously considered the impact a demographic variable, such as gender, can have on the association between HRV and the heart period. A prior meta-analysis showed women to have greater HRV compared to men despite having shorter IBI and higher heart rate (HR). Thus, it is plausible that men and women differ in the association between HRV and HR/IBI. Thus, the present study investigates the potential moderating effect of gender on the association between HRV and indices of cardiac chronotropy, including both HR and IBI. Data from 633 participants (339 women) were available for analysis. Cardiac measures were assessed during a 5-min baseline-resting period. HRV measures included the standard deviation of inter-beat-intervals, root mean square of successive differences, and autoregressive high frequency power. Moderation analyses showed gender significantly moderated the association between all HRV variables and both HR and IBI (each p < 0.05). However, results were not consistent when using recently recommended HRV variables "adjusted" for IBI. Overall, the current investigation provides data illustrating a differential association between HRV and the heart period based on gender. Substantial neurophysiological evidence support the current findings; women show greater sensitivity to acetylcholine compared to men. If women show greater sensitivity to acetylcholine, and acetylcholine increases HRV and the heart period, then the association between HRV and the heart period indeed should be stronger in women compared to men. Taken together, these data suggest that routine "adjustments" to HRV for the heart period are unjustified and problematic at best. As it relates to the application of future HRV research, it is imperative that researchers continue to consider the potential impact of gender.

Multi-scale mechanical and morphological characterisation of sintered porous magnesium-based scaffolds for bone regeneration in critical-sized defects.

Magnesium (Mg) and its alloys are very promising degradable, osteoconductive and osteopromotive materials to be used as regenerative treatment for critical-sized bone defects. Under load-bearing conditions, Mg alloys must display sufficient morphological and mechanical resemblance to the native bone they are meant to replace to provide adequate support and enable initial bone bridging. In this study, unique highly open-porous Mg-based scaffolds were mechanically and morphologically characterised at different scales. In situ X-ray computed tomography (XCT) mechanics, digital volume correlation (DVC), electron microscopy and nanoindentation were combined to assess the influence of material properties on the apparent (macro) mechanics of the scaffold. The results showed that Mg exhibited a higher connected structure (38.4mm-3 and 6.2mm-3 for Mg and trabecular bone (Tb), respectively) and smaller spacing (245µm and 629µm for Mg and Tb, respectively) while keeping an overall appropriate porosity of 55% in the range of trabecular bone (30-80%). This fully connected and highly porous structure promoted lower local strain compared to the trabecular bone structure at material level (i.e. -22067 ± 8409µÎµ and -40120 ± 18364µÎµ at 6% compression for Mg and trabecular bone, respectively) and highly ductile mechanical behaviour at apparent level preventing premature scaffold failure. Furthermore, the Mg scaffolds exceeded the physiological strain of bone tissue generated in daily activities such as walking or running (500-2000µÎµ) by one order of magnitude. The yield stress was also found to be close to trabecular bone (2.06MPa and 6.67MPa for Mg and Tb, respectively). Based on this evidence, the study highlights the overall biomechanical suitability of an innovative Mg-based scaffold design to be used as a treatment for bone critical-sized defects. STATEMENT OF SIGNIFICANCE: Bone regeneration remains a challenging field of research where different materials and solutions are investigated. Among the variety of treatments, biodegradable magnesium-based implants represent a very promising possibility. The novelty of this study is based on the characterisation of innovative magnesium-based implants whose structure and manufacturing have been optimised to enable the preservation of mechanical integrity and resemble bone microarchitecture. It is also based on a multi-scale approach by coupling high-resolution X-ray computed tomography (XCT), with in situ mechanics, digital volume correlation (DVC) as well as nano-indentation and electron-based microscopy imaging to define how degradable porous Mg-based implants fulfil morphological and mechanical requirements to be used as critical bone defects regeneration treatment.

Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development.

Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be extremely beneficial. Therefore, the option of conducting HCTs to accelerate SARS-CoV-2 vaccine development should be preserved. As HCTs require many months of preparation, we recommend an immediate effort to (1) establish guidelines for HCTs for COVID-19; (2) take the first steps toward HCTs, including preparing challenge virus and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs.

HIV-hepatitis co-infection in a rural community in Northern Nigeria.

INTRODUCTION: HIV, hepatitis B and hepatitis C pose a public health challenge in sub-Saharan Africa and there are only few studies on co-infection of these viruses done in rural areas in Northern Nigeria. This study provides a rural perspective on HIV-hepatitis co-infection in a Northern Nigerian community. METHODS: this cross-sectional study was carried out amongst people living with HIV/AIDS (PLWHA) in a rural community hospital over a three-month period. Socio-demographic data and other relevant information were obtained from the participants and case notes using an interviewer-administered questionnaire. Hepatitis B surface antigen and antibody to Hepatitis C virus were assayed from serum using enzyme-linked immunosorbent assay (ELISA) kits developed by LabACON®. Chi-square test was used to compare categorical variables and logistic regression modelling was used to determine correlates of co-infection in the population. RESULTS: a total of 281 individuals participated in the study. The prevalence of Hepatitis B co-infection, Hepatitis C co-infection and triple infection was 6.0%, 14.6% and 1.1% respectively. Using Chi-square test, none of the socio-demographic characteristics, WHO Clinical Stage, viral suppression had significant association with Hepatitis B co-infection, however marital status was significantly associated with Hepatitis C co-infection and level of education was significantly associated with triple infection (p < 0.05). Logistic regression modelling generated no significant results. CONCLUSION: co-infection of viral hepatitis (particularly Hepatitis C) in PLWHA is common in rural Northern Nigeria, and significant correlates include lack of formal education and being married. There is need for provider-initiated routine counselling and screening of PLWHA for viral hepatitis, with adequate follow-up and treatment of co-infected individuals and Hepatitis B vaccination for those without co-infection.

Stereotype threat, trait perseveration, and vagal activity: evidence for mechanisms underpinning health disparities in Black Americans.

Objective: Black Americans (BAs) are at an elevated risk for morbidity and mortality in comparison to White Americans (WAs). Racial stressors are a common occurrence in American culture and is theorized to contribute to these disparities. When race-focused, stereotype threat (ST) is considered to be a factor that is detrimental to health in BAs; however few studies have directly investigated the impact of a ST manipulation on physiological function. Furthermore, it is proposed that racial stressors such as ST may have prolonged effects when more likely to perseverate (e.g. rumination) over the stressor and thus, those with greater trait perseveration may be more affected by ST. We sought to explore the impact of ST and trait perseveration on changes in vagus nerve activity - an indication of adaptive psychological and physiological well-being - as indexed by vagally mediated heart rate variability (vmHRV). Design: Forty-three (24 females, mean age of 20, standard deviation of 3 years) apparently healthy BA individuals were randomly assigned to one of three experimental conditions in which they received either implicit (subtle), explicit (blatant), or no ST priming (control condition), prior to completing a cognitive task. Resting vmHRV was assessed both at baseline (pre-task) and recovery (post-task). Results: BAs in the explicit ST condition exhibited the greatest decrease in vmHRV in comparison to the control group from pre- to post-task. BAs with moderate to high levels of trait perseveration showed the greatest decrease in vmHRV from pre- to post-task in comparison to those with lower levels of trait perseveration and BAs in the control group. Conclusion: These data suggest that racial ST, especially when explicit and coupled with trait perseveration, can decrease vagal activity, as indexed by decreased vmHRV, which when experienced frequently can have significant consequences for health and longevity in BAs.

Tranexamic acid use during total hip arthroplasty: A single center retrospective analysis.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent that has shown promise in reducing blood loss during total hip arthroplasty (THA). Several studies have reported side effects of high-dose TXA administration, including myocardial infarction (MI), thromboembolic events, and seizures. These possible side effects have prevented the widespread adoption of TXA in the surgical community. METHODS: We conducted a retrospective chart review of 564 primary and revision THAs performed at a single academic center. Surgical patients received either no TXA or 1 g IV TXA at the beginning of surgery followed by a second bolus just before the surgical wound closure, at the surgeon's discretion. We analyzed differences in hemoglobin (Hb), hematocrit (Hct), estimated blood loss (EBL), and adverse events in patients receiving TXA versus patients not receiving TXA up to 2 days following surgery. RESULTS: Significantly higher Hb and Hct values were found across all time points among patients undergoing primary posterior or revision THA who had received TXA. In addition, transfusion rates were significantly decreased in both primary posterior THAs and revision THAs when TXA was administered. Patients who received TXA experienced significantly fewer adverse events than those who did not for all surgery types. CONCLUSION: Administration of low-dose intravenous (IV) and intra-articular (IA) TXA does not appear to increase rates of adverse events and may be effective in minimizing blood loss, as reflected by Hb and Hct values following THA.

Advanced Analgesic Drug Delivery and Nanobiotechnology.

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Extracorporeal life support for refractory ventricular tachycardia.

Extracorporeal life support (ECLS) is a very effective bridging therapy in patients with refractory ventricular tachycardia (VT) associated with cardiogenic shock. A moribund patient in extremis, is not amenable to optimization by standard ACC/AHA guidelines. New approaches and novel salvage techniques are necessary to improve outcomes in patients with refractory clinical settings such as malignant ventricular arrhythmias, cardiac arrest, cardiogenic shock and/or pulmonary failure until further management options are explored. Data base searches were done using key words such as ECLS, VT, cardiac arrest, VT ablation, venoarterial extra-corporeal membrane oxygenation (VA-ECMO). The use of ECLS has been described in a few case reports to facilitate VT ablation for incessant VT refractory to medical therapy. For patients with, out-of- hospital ventricular fibrillation (VF) and VT, Minnesota Resuscitation Consortium has implemented emergent advanced perfusion and reperfusion strategy, followed by coronary angiography and primary coronary intervention to improve outcome. The major indications for ECLS are cardiogenic shock related to acute myocardial infarction, myocarditis, post embolic acute cor pulmonale, drug intoxication and post cardiac arrest syndrome with the threat of multi-organ failure. ECLS permits the use of negative inotropic antiarrhythmic drug therapy, facilitates the weaning of catecholamine administration, thereby ending the vicious cycle of catecholamine driven electric storm. ECLS provides hemodynamic support during ablation procedure, while mapping and induction of VT is undertaken. ECLS provides early access to cardiac catheterization laboratory in patients with cardiac arrest due to shockable rhythm. The current evidence from literature, supports the use of ECLS to ensure adequate vital organ perfusion in patients with refractory VT. ECLS is a safe, feasible and effective therapeutic option when conventional therapies are insufficient to support cardiopulmonary function. A highly driven multidisciplinary team approach is essential to accomplish this task.