A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions

AbstractMorphogenesis of influenza virus is a poorly understood process that produces two types of enveloped virion: ∼100-nm spheres and similar diameter filaments that reach 20 μm in length. Spherical particles assemble at plasma membrane lipid rafts in a process independent of microfilaments. The budding site of filamentous virions is hitherto uncharacterised but their formation involves the actin cytoskeleton. We confirm microfilament involvement in filamentous budding and show that after disruption of cortical actin by jasplakinolide, HA, NP, and M1 redistributed around β-actin clusters to form novel annular membrane structures. HA in filamentous virions and jasplakinolide-induced annuli was detergent insoluble at 4°C. Furthermore, in both cases HA partitioned into low buoyant density detergent-insoluble glycolipid domains, indicating that filamentous virions and annuli contain reorganised lipid rafts. We propose that the actin cytoskeleton is required to maintain the correct organisation of lipid rafts for incorporation into budding viral filaments

Whole Body Fuel Use: A Preliminary Study of Carbohydrate and Fat Oxidation During Water Exercise

The purpose of this investigation was to measure energy expenditure and whole body carbohydrate and fat oxidation during shallow water exercise (SWE; submerged to axillary level). The level of energy expenditure and the relative contribution of fuels (e.g., carbohydrate [CHO], fat) depends on the intensity of exercise effort. This descriptive study addressed two questions: (1) what is the energy expenditure of performing SWE over a range of intensities; and (2) how does the rate of CHO and fat usage change with increasingly more demanding SWE efforts. Five healthy females (ages 18 to 26 years) performed five submaximal and one maximal SWE bout based on perceived effort (Borg Scale). Indirect calorimetry (Parvo-Medic metabolic analyzer) was employed to assess metabolic response while heart rate (HR) was monitored via telemetry (Polar technology). For perception of efforts ranging from very light (~50 percent HR peak) to very hard (~88 percent HR peak), the rate of energy expenditure ranged from 3.5+0.7 to 10.5+1.3 kilocalories per minute (Kcal.min-1), while the maximal SWE effort elicited a metabolic response of 13.2+1.7 Kcal.min-1 (~ 10 X resting metabolic rate). From very light to very hard, the rate of CHO oxidation increased from 2.0+1.0 to 9.4+1.8 Kcal.min-1 (~370 percent increase), while fat oxidation remained variable among the SWE efforts. In conclusion, carbohydrate oxidation plays an increasingly more important role as a fuel source during SWE efforts that require a high rate of energy expenditure. Furthermore, this study provides insight into the energy requirements of SWE, a mode of exercise that is becoming more popular

Cardiorespiratory Responses to High Intensity Interval Shallow Water Exercise

The purpose of this study was to investigate the cardiorespiratory responses to shallow water, high intensity interval exercise (SW-HIIE). Interestingly, no studies have investigated the physiological responses of performing HIIE in a water medium. Thus, the main question of this investigation was the following: What is the physiological load imposed on the human body during an acute SW-HIIE session? Physically active females, n=9 and 26+6 yrs, volunteered for this descriptive study. Volunteers performed a familiarization trial, an incremental maximal shallow water exercise test, and a SW-HIIE session. Participants were submerged to ~75 percent of stature (axillary level). SW-HIIE consisted of 4 X 4 minute segments with one minute recovery in between each segment. Each segment consisted of 8 X 20 seconds of maximal physical effort with 10 seconds of rest between each effort. Indirect calorimetry (Parvo-Medic metabolic analyzer) was employed to assess metabolic response and heart rate was monitored via telemetry (Polar technology). SW-HIIE elicited an overall oxygen uptake response of 2.0+0.2 lO2.min-1 (73+5% of peak aerobic capacity), nearly eight times above resting metabolic rate, while overall heart rate (HR) response was 156+8 bpm (86+2% HR peak). In conclusion, the SW-HIIE session elicited cardiorespiratory responses that would be classified as vigorous on the intensity scale according to the American College of Sports Medicine’s guidelines for exercise prescription, suggesting that an acute bout of SW-HIIE imposes a great physiological load on the human body

Ozone depletion and chlorine loading potentials

The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere

Paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): an e-survey of the experiences of parents and clinicians.

BackgroundLittle evidence exists about parental satisfaction and their influence on referral to paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT).AimThis study aimed to examine the experiences of parents, children and clinicians of OPAT at a large tertiary children's hospital.MethodA prospective e-survey, using closed and open questions, of parents (n = 33) of 33 children who had received OPAT (3 children completed a survey), and clinicians (n = 31) involved in OPAT at a tertiary hospital. Data were collected September 2016 to July 2018.ResultsData were analysed using simple descriptive statistics. The results show that OPAT offered benefits (less stress, re-establishment of family life) compared to hospital-based treatment for parents and children, although some were anxious. Clinicians' referral judgements were based on child, home, and clinical factors. Some clinicians found the process of referral complex.ConclusionMost parents and children were satisfied with the OPAT service and preferred the option of home-based treatment as it promoted the child's comfort and recovery and supported family routines

Activation mapping in patients with coronary artery disease with multiple ventricular tachycardia configurations: Occurrence and therapeutic implications of widely separate apparent sites of origin

Catheter or intraoperative activation mapping studies, or both, were performed in 17 patients with coronary artery disease with two to four distinct configurations of ventricular tachycardia, resistant to a mean of 12.1 ± 6.0 antiarrhythmic drug trials per patient. Mapping studies were performed to guide anticipated surgical ablation of arrhythmias. Activation map data were adequate to determine sites of origin of 30 (64%) of 47 observed tachycardia configurations. These 30 ventricular tachycardias (26 observed clinically) were mapped to 22 separate endocardial sites of origin. Sites of origin of distinct tachycardias were identical or closely adjacent (within 3 cm) in six patients and widely separate (≥4 cm) in eight patients (47% of the group). Activation maps were not adequate to determine sites of origin of 17 (36%) of the 47 tachycardias, including all configurations in three patients.Fifteen patients underwent surgery for control of ventricular tachycardia: aggressive, map-guided endocardial resection (mean 26.5 ± 14.2 cm2) in 12 patients with identified sites of tachycardia origin and extensive resection of visible endocardial scar (2 patients) or encircling endocardial ventriculotomy (1 patient) in those in whom the sites of origin of all clinical tachycardias remained undetermined. Two inoperable patients were treated with amiodarone. During postoperative electrophysiologic tests (11 of 13 surgical survivors), ventricular tachyarrhythmias were initially uninducible in only 4 of 11 patients. However, in two patients only nonclinical arrhythmias (ventricular flutter) were induced. Six (21%) of 29 clinical tachycardias whose sites of origin were either not determined or not resected (right septum or papillary muscle) remained inducible in five patients. Using previously ineffective antiarrhythmic drugs, initially inducible arrhythmias became uninducible (two patients), or harder to induce than preoperatively (five patients). As a result of surgical resections alone or in combination with previously ineffective drugs (and amiodarone in two inoperable patients), there were no recurrences of ventricular tachycardia in 14 (93%) of 15 patients discharged during 19.0 ± 14.3 months of follow-up study.Thus, activation mapping may commonly reveal separate apparent sites of origin for clinically observed, morphologically distinct, highly drug-refractory ventricular tachycardias in patients with coronary artery disease with multiple tachycardia configurations. Extensive surgical resection of identified sites of origin may be required to ablate arrhythmias in these patients. Tachycardias whose sites of origin are not identified or resected may remain inducible. However, aggressive surgical excisions may alter regions involved in the genesis or maintenance of these arrhythmias because they become more difficult to induce postoperatively, more amenable to drug therapy and do not recur

MISSION Diversion & Recovery for Traumatized Veterans (MISSION DIRECT VET): Early Findings and Lessons Learned

MISSION DIRECT VET is a SAMHSA- funded, court based diversion program targeting veterans in Massachusetts with trauma-related mental health and substance use problems. MISSION-DIRECT VET seeks to: Reduce criminal justice involvement Treat mental health, substance abuse and other trauma related symptoms Use a systematic wrap-around model Provide care coordination, peer support and trauma informed services Develop interagency partnerships to serve veterans with co-occurring disorder