Qualitative Analysis of Multiple Sources and Dimensions of Stigma Among Older Adults Living With HIV Infection Released From Corrections.

While sources of stigma associated with HIV, incarceration, and aging have been explored separately, the concurrent effects of these multiple sources have been understudied. We conducted in-depth interviews with 48 older adults over 50 years of age with HIV infection who were returning from correctional settings concerning their experiences of stigma. Participants described HIV-related stigma substantially more often than incarceration-related stigma and a greater number of stigma experiences as time passed from release. Anticipated stigma experiences were frequently associated with HIV. Enacted stigma was often related to incarceration. Internalized stigma was associated with both HIV and incarceration. However, participants often described aging as a positive experience of gaining wisdom and control over their life. The findings indicated that multiple sources of stigma affect different dimensions of stigma. Postrelease interventions may benefit from addressing increasing experiences of stigma in the rapidly growing population of older adults living with HIV with a history of incarceration.

A Phase I/II Placebo-Controlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients With Dry Eye Disease.

PURPOSE: To determine whether DNase eye drops have the potential to reduce signs and symptoms of dry eye disease (DED). METHODS: A placebo-controlled, randomized clinical trial was performed to compare the safety and efficacy of DNase eye drops 0.1% four times a day for 8 weeks in patients with severe tear deficient DED. The change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (Ocular Surface Disease Index [OSDI] score, corneal and conjunctival staining) were analyzed between baseline and week 8. RESULTS: Tolerability and adverse events were similar in placebo group and DNase group. Within the DNase group (but not placebo group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 compared with baseline. The OSDI score also showed a significant median reduction of 27.3 at week 8 compared with baseline within the DNase group. The median reduction in corneal staining and mucoid debris/strands was significantly greater in the DNase group as compared with the placebo group. In the DNase group, the median reduction in OSDI (-20.75) was more than placebo group (-8.43); however, the difference between groups was borderline significant. CONCLUSIONS: In this pilot study, treatment of severe tear deficient DED patients with DNase eye drops appears safe, well tolerated, and has the potential to reduce the severity of signs and symptoms. TRANSLATIONAL RELEVANCE: Data from this pilot clinical trial demonstrate the therapeutic potential of DNase eye drops in dry eye disease, possibly due to degradation neutrophil extracellular traps (NETs) from the ocular surface.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival.

OBJECTIVES: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN: Multicenter prospective study of in-hospital cardiac arrest. SETTING: Five medical centers in the United States and the United Kingdom. PATIENTS: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95-100) and 93% positive predictive value (95% CI, 66-100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1-2 (area under the curve, 0.79; 95% CI, 0.70-0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46-95), 72% specificity (95% CI, 65-79), and 98% negative predictive value (95% CI, 93-100) for cerebral performance category 1-2. CONCLUSIONS: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

Exceptional running and turning performance in a mite.

The Southern California endemic mite Paratarsotomus macropalpis was filmed in the field on a concrete substrate and in the lab to analyze stride frequency, gait and running speed under different temperature conditions and during turning. At ground temperatures ranging from 45 to 60 °C, mites ran at a mean relative speed of 192.4 ± 2.1 body lengths (BL) s(-1), exceeding the highest previously documented value for a land animal by 12.5%. Stride frequencies were also exceptionally high (up to 135 Hz), and increased with substrate temperature. Juveniles exhibited higher relative speeds than adults and possess proportionally longer legs, which allow for greater relative stride lengths. Although mites accelerated and decelerated rapidly during straight running (7.2 ± 1.2 and -10.1 ± 2.1 m s(-2), respectively), the forces involved were comparable to those found in other animals. Paratarsotomus macropalpis employs an alternating tetrapod gait during steady running. Shallow turns were accomplished by a simple asymmetry in stride length. During tight turns, mites pivoted around the tarsus of the inside third leg (L3), which thus behaved like a grappling hook. Pivot turns were characterized by a 42% decrease in turning radius and a 40% increase in angular velocity compared with non-pivot turns. The joint angle amplitudes of the inner L2 and L3 were negligible during a pivot turn. While exceptional, running speeds in P. macropalpis approximate values predicted from inter-specific scaling relationships.

Secondhand Smoke Exposure and Illness Severity among Children Hospitalized with Pneumonia.

OBJECTIVE: To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the child's home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS: Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION: Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity.

Cerebral oximetry levels during CPR are associated with return of spontaneous circulation following cardiac arrest: an observational study.

OBJECTIVES: Cerebral oximetry using near-infrared spectroscopy measures regional cerebral oxygen saturation (rSO2) non-invasively and may provide information regarding the quality of cerebral oxygen perfusion. We determined whether the level of rSO2 obtained during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival in Emergency Department (ED) patients presenting with cardiac arrest. METHODS: We conducted a retrospective, observational study of adult ED patients presenting at an academic medical centre with cardiac arrest in whom continuous cerebral oximetry was performed. Demographic and clinical data including age, gender, presenting rhythm and mean rSO2 readings were abstracted. Cerebral oxygenation was measured with a commercially available oximeter. RESULTS: A convenience study sample included 59 patients ages 18-102 years (mean age 68.7±14.9 years); 50 (84.7%) were men. Presenting rhythms included pulseless electrical activity (21), asystole (20) and ventricular fibrillation/tachycardia (17). 24 patients (40.6%) had ROSC and only 1 (1.7%) survived to hospital discharge. Patients with and without ROSC were similar in age and presenting cardiac rhythms. The mean of mean rSO2 levels was higher in patients with ROSC, 43.8 (95% CI 40.1 to 47.6) compared with those without ROSC, 34.2 (95% CI 30.6 to 37.8); p=0.001. 91.7% of patients with ROSC had a rSO2 of 30% or greater compared with 62.9% in those without ROSC (p=0.01). The area under the curve for mean rSO2 as a predictor of ROSC was 0.76 (95% CI 0.64 to 0.89). CONCLUSIONS: In ED patients with cardiac arrest higher cerebral oxygen saturations are associated with higher rates of ROSC.

A feasibility study of cerebral oximetry monitoring during the post-resuscitation period in comatose patients following cardiac arrest.

BACKGROUND: One of the major causes of death and neurological injury after cardiac arrest is delayed ischemia combined with oxygen free radical mediated reperfusion injury. Consequently determining the optimal balance between oxygen delivery and uptake in the brain using a reliable non-invasive monitoring system during the post-resuscitation period is of importance. In this observational study, we evaluated the feasibility of using cerebral oximetry during the post-resuscitation period in order to identify changes in regional cerebral oxygen saturation (rSO2) and its association with survival to discharge. METHODS: 21 consecutive patients admitted to the intensive care units following cardiac arrest had cerebral oximetry monitoring carried out for 48 h. Mean rSO2 values were collected during the first 24h and then again during the subsequent 24-48 h of the post-resuscitation period. RESULTS: 43% (n=9) patients survived to hospital discharge and 57% (n=12) died. Amongst all patients the median (IQR) rSO2% was 65.5% (62.6-68.2) in the first 24-h following ROSC and increased to 72.1% (64.6-73.7) (p=0.11) in the subsequent 24-48 h. The median (IQR) rSO2% during the first 24 h in patients who survived to discharge compared to those who did not survive were significantly higher 68.2% (66.0-71.0) vs. 62.9% (56.5-66.0), p=0.01). During the subsequent 24-48 h period, while a difference in the rSO2 between survivors and non-survivors was noted, this did not achieve statistical significance (median (IQR): 73.7 (70.2-74.0) vs. 66.5 (58.2-72.1), p=0.11). CONCLUSIONS: Our study indicates that the use of cerebral oximetry is feasible during the post resuscitation period after cardiac arrest. Further studies are needed to determine whether cerebral oximetry may be used as a novel non-invasive monitoring system to evaluate changes in the balance between cerebral oxygen delivery and uptake during the post-resuscitation period.

A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*.

OBJECTIVE: A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. DESIGN: An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. SETTING: Tertiary medical center. PATIENTS: In-hospital cardiac arrest patients (n = 34). MAIN RESULTS: Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). CONCLUSIONS: The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

A pilot study examining the role of regional cerebral oxygen saturation monitoring as a marker of return of spontaneous circulation in shockable (VF/VT) and non-shockable (PEA/Asystole) causes of cardiac arrest.

BACKGROUND: Non-invasive monitoring of cerebral perfusion and oxygen delivery during cardiac arrest is not routinely utilized during cardiac arrest resuscitation. The objective of this study was to investigate the feasibility of using cerebral oximetry during cardiac arrest and to determine the relationship between regional cerebral oxygen saturation (rSO2) with return of spontaneous circulation (ROSC) in shockable (VF/VT) and non-shockable (PEA/asystole) types of cardiac arrest. METHODS: Cerebral oximetry was applied to 50 in-hospital and out-of-hospital cardiac arrest patients. RESULTS: Overall, 52% (n=26) achieved ROSC and 48% (n=24) did not achieve ROSC. There was a significant difference in mean±SD rSO2% in patients who achieved ROSC compared to those who did not (47.2±10.7% vs. 31.7±12.8%, p<0.0001). This difference was observed during asystole (median rSO2 (IQR) ROSC versus no ROSC: 45.0% (35.1-48.8) vs. 24.9% (20.5-32.9), p<0.002) and PEA (50.6% (46.7-57.5) vs. 31.6% (18.8-43.3), p=0.02), but not in the VF/VT subgroup (43.7% (41.1-54.7) vs. 42.8% (34.9-45.0), p=0.63). Furthermore, it was noted that no subjects with a mean rSO2<30% achieved ROSC. CONCLUSIONS: Cerebral oximetry may have a role as a real-time, non-invasive predictor of ROSC during cardiac arrest. The main utility of rSO2 in determining ROSC appears to apply to asystole and PEA subgroups of cardiac arrest, rather than VF/VT. This observation may reflect the different physiological factors involved in recovery from PEA/asytole compared to VF/VT. Whereas in VF/VT, successful defibrillation is of prime importance, however in PEA and asytole achieving ROSC is more likely to be related to the quality of oxygen delivery. Furthermore, a persistently low rSO2 <30% in spite of optimal resuscitation methods may indicate futility of resuscitation efforts.

Therapeutic angiogenesis: a new treatment approach for ischemic heart disease--Part II.

Angiogenesis is the biologic process of forming new blood vessels and is being investigated as an innovative therapeutic approach to help manage ischemic heart disease and peripheral vascular disease. Research studies have identified various angiogenic growth factors and progenitor cells that can enhance new blood vessel formation. This is Part II of an article that began publication in the July/August issue of Cardiology in Review. Preclinical investigations in animal models have explored the potential use of growth factors with and without progenitor cells to treat myocardial ischemia. The results of clinical trials with growth factor infusions and gene therapy techniques to enhance growth factor production have shown some promise, but therapeutic angiogenesis remains at an early stage of development.

Therapeutic angiogenesis: a new treatment approach for ischemic heart disease--part I.

Angiogenesis is the biologic process of forming new blood vessels and is being investigated as an innovative therapeutic approach to help manage ischemic heart disease and peripheral vascular disease. Research studies have identified various angiogenic growth factors and progenitor cells that can enhance new blood vessel formation. Preclinical investigations in animal models have explored the potential use of growth factors with and without progenitor cells to treat myocardial ischemia. The results of clinical trials with growth factor infusions and gene therapy techniques to enhance growth factor production have shown some promise, but therapeutic angiogenesis remains at an early stage of development.

Neuromechanics: an integrative approach for understanding motor control.

Neuromechanics seeks to understand how muscles, sense organs, motor pattern generators, and brain interact to produce coordinated movement, not only in complex terrain but also when confronted with unexpected perturbations. Applications of neuromechanics include ameliorating human health problems (including prosthesis design and restoration of movement following brain or spinal cord injury), as well as the design, actuation and control of mobile robots. In animals, coordinated movement emerges from the interplay among descending output from the central nervous system, sensory input from body and environment, muscle dynamics, and the emergent dynamics of the whole animal. The inevitable coupling between neural information processing and the emergent mechanical behavior of animals is a central theme of neuromechanics. Fundamentally, motor control involves a series of transformations of information, from brain and spinal cord to muscles to body, and back to brain. The control problem revolves around the specific transfer functions that describe each transformation. The transfer functions depend on the rules of organization and operation that determine the dynamic behavior of each subsystem (i.e., central processing, force generation, emergent dynamics, and sensory processing). In this review, we (1) consider the contributions of muscles, (2) sensory processing, and (3) central networks to motor control, (4) provide examples to illustrate the interplay among brain, muscles, sense organs and the environment in the control of movement, and (5) describe advances in both robotics and neuromechanics that have emerged from application of biological principles in robotic design. Taken together, these studies demonstrate that (1) intrinsic properties of muscle contribute to dynamic stability and control of movement, particularly immediately after perturbations; (2) proprioceptive feedback reinforces these intrinsic self-stabilizing properties of muscle; (3) control systems must contend with inevitable time delays that can simplify or complicate control; and (4) like most animals under a variety of circumstances, some robots use a trial and error process to tune central feedforward control to emergent body dynamics.

Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo.

Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 microg.kg(-1).min(-1)); (ii) 8-Br-cGMP (50 microg.kg(-1).min(-1)); or (iii) NO synthase inhibitor L-nitro-argininemethylester (40 microg.kg(-1).min(-1); n = 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 +/- 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 +/- 13%), compared with control (167 +/- 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 +/- 7%) and 8-Br-cGMP (120 +/- 11%), compared with control (165 +/- 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and L-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors.

Multistep regulation of membrane insertion of the fusion peptide of Semliki Forest virus.

A prevailing model for virus membrane fusion proteins has been that the hydrophobic fusion peptide is hidden in the prefusion conformation, becomes exposed once the fusion reaction is triggered, and then either inserts into target membranes or is rapidly inactivated. This model is in general agreement with the structure and mechanism of class I fusion proteins, such as the influenza virus hemagglutinin. We here describe studies of the class II fusion protein E1 from the alphavirus Semliki Forest virus (SFV). SFV fusion is triggered by low pH, which releases E1 from its heterodimeric interaction with the E2 protein and induces the formation of a stable E1 homotrimer. The exposure and target membrane interaction of the E1 fusion peptide (residues 83 to 100) were followed using a monoclonal antibody (MAb E1f) mapping to E1 residues 85 to 95. In agreement with the known structure of SFV and other alphaviruses, the fusion peptide was shielded in native SFV particles and exposed when E1-E2 dimer dissociation was triggered by acidic pH. In contrast, the fusion peptide on purified E1 ectodomains (E1(*)) was fully accessible at neutral pH. Functional assays showed that MAb E1f binding at neutral pH prevented subsequent low-pH-triggered E1(*) interaction with target membranes and trimerization. E1(*) was not inactivated by low pH when treated either in the absence of target membranes or in the presence of fusion-inactive cholesterol-deficient liposomes. Thus, the membrane insertion of the E1 fusion peptide is regulated by additional low-pH-dependent steps after exposure, perhaps involving an E1-cholesterol interaction.

Purification and crystallization reveal two types of interactions of the fusion protein homotrimer of Semliki Forest virus.

The fusion proteins of the alphaviruses and flaviviruses have a similar native structure and convert to a highly stable homotrimer conformation during the fusion of the viral and target membranes. The properties of the alpha- and flavivirus fusion proteins distinguish them from the class I viral fusion proteins, such as influenza virus hemagglutinin, and establish them as the first members of the class II fusion proteins. Understanding how this new class carries out membrane fusion will require analysis of the structural basis for both the interaction of the protein subunits within the homotrimer and their interaction with the viral and target membranes. To this end we report a purification method for the E1 ectodomain homotrimer from the alphavirus Semliki Forest virus. The purified protein is trimeric, detergent soluble, retains the characteristic stability of the starting homotrimer, and is free of lipid and other contaminants. In contrast to the postfusion structures that have been determined for the class I proteins, the E1 homotrimer contains the fusion peptide region responsible for interaction with target membranes. This E1 trimer preparation is an excellent candidate for structural studies of the class II viral fusion proteins, and we report conditions that generate three-dimensional crystals suitable for analysis by X-ray diffraction. Determination of the structure will provide our first high-resolution views of both the low-pH-induced trimeric conformation and the target membrane-interacting region of the alphavirus fusion protein.

The fusion peptide of Semliki Forest virus associates with sterol-rich membrane domains.

Semliki Forest virus (SFV) is an enveloped alphavirus whose membrane fusion is triggered by low pH and promoted by cholesterol and sphingolipid in the target membrane. Fusion is mediated by E1, a viral membrane protein containing the putative fusion peptide. Virus mutant studies indicate that SFV's cholesterol dependence is controlled by regions of E1 outside of the fusion peptide. Both E1 and E1*, a soluble ectodomain form of E1, interact with membranes in a reaction dependent on low pH, cholesterol, and sphingolipid and form highly stable homotrimers. Here we have used detergent extraction and gradient floatation experiments to demonstrate that E1* associated selectively with detergent-resistant membrane domains (DRMs or rafts). In contrast, reconstituted full-length E1 protein or influenza virus fusion peptide was not associated with DRMs. Methyl beta-cyclodextrin quantitatively extracted both cholesterol and E1* from membranes in the absence of detergent, suggesting a strong association of E1* with sterol. Monoclonal antibody studies demonstrated that raft association was mediated by the proposed E1 fusion peptide. Thus, although other regions of E1 are implicated in the control of virus cholesterol dependence, once the SFV fusion peptide inserts in the target membrane it has a high affinity for membrane domains enriched in cholesterol and sphingolipid.