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Made available in DSpace on 2022-04-30T05:16:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-06 Considering the known different mode of action of antimicrobial peptides in zwitterionic and anionic cell membranes, the present work compares the action of the antimicrobial peptide K0-W6-Hya1 (KIFGAIWPLALGALKNLIK-NH2) with zwitterionic and negatively charged model membranes, namely, liposomes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) membranes, and a mixture of the two. Differential scanning calorimetry (DSC), steady state fluorescence of the Trp residue, dynamic light scattering (DLS), and measurement of the leakage of an entrapped fluorescent dye (carboxyfluorescein, CF) were performed with large unilamellar vesicles (LUVs). All techniques evidenced the different action of the peptide in zwitterionic and anionic vesicles. Trp fluorescence spectroscopy shows that the differences are related not only to the partition of the cationic peptide in zwitterionic and anionic membranes, but also to the different penetration depth of the peptide into the lipid bilayers: Trp goes deeper into negatively charged membranes, both in the gel and fluid phases, than into zwitterionic ones. DSC shows that the peptide is strongly attached to anionic bilayers, giving rise to the coexistence of two different lipid regions, one depleted of peptide and another one peptide-disturbed, possibly a stable or transient polar pore, considering the leakage of CF. This contrasts with the homogeneous effect produced by the peptide in zwitterionic membranes, probably related to peptide-membrane diffusion. Moreover, in mixed bilayers (PC:PG), the peptide sequesters negatively charged lipids, creating peptide-rich anionic lipid regions, strongly disturbing the membrane. The distinct structural interaction displayed by the peptide in PC and PG membranes could be related to the different mechanisms of action of the peptide in anionic prokaryotic and zwitterionic eukaryotic cell membranes. Instituto de Física Universidade de Sao Paulo Departamento de Biofísica Universidade Federal de Sao Paulo Departamento de Bioquímica e Biologia Molecular Instituto de Ciências Biológicas Universidade Federal de Goiás Instituto de Química Universidade Estadual de Sao Paulo Instituto de Química Universidade Estadual de Sao Paulo

Under certain conditions, biological membranes exhibit resistance to solubilization, even at high detergent concentration. These insoluble fragments are enriched in sphingolipids, cholesterol, and certain proteins having a preference for more organized environments. Here we investigated the effect of detergent Triton X-100 (TX-100) on raft-like lipid mixtures composed of POPC (palmitoyl oleoyl phosphatidylcholine, an unsaturated lipid), SM (sphingomyelin, a saturated lipid), and cholesterol, focusing on the detergent-induced phase separation at subsolubilizing concentration and the extent of solubilization at higher concentration. Giant unilamellar vesicles (GUVs) of POPC/SM/chol containing a fluorescent probe known to prefer the liquid-disordered phase were prepared and observed with fluorescence microscopy. A phase diagram constructed in the presence and absence of 0.1 mM TX-100 showed that the detergent induces macroscopic liquid-ordered/liquid-disordered (Lo/Ld) phase separation over a wide range of membrane composition, indicating that TX-100 has the ability to rearrange the lateral heterogeneity of the lipid mixture. The extent of solubilization of the POPC/SM/chol GUVs was quantified by measuring the vesicle size before and after the injection of a high concentration of TX-100. In parallel, the solubilization extent of large unilamellar vesicles (LUVs) was assessed by turbidity measurements. The extent of solubilization decreases significantly as the fractions of SM and cholesterol in the mixture increase. The origin of the detergent resistance is the low partitioning of TX-100 in cholesterol-rich membranes, especially in SM-containing ones, as evidenced by isothermal titration calorimetry experiments on LUVs. Our results provide a guide to future research on the effects of TX-100 on raft-like lipid mixtures.

Objective: The objective of this research is to study the feasibility of measuring behavioral indicators that reflect effects of infrastructure and interaction with other road users. Methods: An observation study was performed using 6 cameras above a separated cycle path next to a road which included a crossing with both cyclists and cars. A learning method based on Single Shot MultiBox Detector was applied to automatically detect the cyclists, and cyclist tracks were determined. Next, kinematic parameters were calculated from the cyclists’ tracks. Amongst others, the cyclists’ intensity, speed, position on the cycle path, and the distance to each other were analyzed for a busy period as well as for a quiet period of the day. Results: With the measurement method developed in this study it is possible to analyze the cyclists’ intensity, the space they use at the cycle path, their average velocity, waiting times, the space and velocity amongst each other, and red light negation. However, collisions were not seen in the dataset analyzed, and the data is not sufficiently accurate to analyze sudden braking actions. Conclusion: It can be concluded that the developed measurement method provides insight of the cyclists’ behavior in such a way that it can already be used for obtaining information to make changes to the infrastructure that will improve the comfort and safety of cyclists. The method could be further developed for doing qualitative comfort and safety analyses, and for doing analyses of the interaction between various types of road participants.

The influences of the hydrophilic chain length, morphology and chemical nature have been probed with regard to the adsorption of model proteins onto the surface of soft nanoparticles (crew-cut micelles and polymersomes). The investigations were based on assemblies manufactured from PEOm-b-PLAn (poly(ethylene oxide)-b-poly(lactic acid)), which is a well-established block copolymer platform towards the manufacturing of drug delivery vehicles, and PHPMAm-b-PDPAn (poly([N-(2-hydroxypropyl)]methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate]), which is pH-responsive and therefore potentially able to target damaged cells in slightly acid microenvironments. Besides, protein adsorption onto PHPMA-stabilized nanoparticles has been seldom explored up-to-date. The morphologies were produced using two different approaches (nanoprecipitation and thin-film hydration) and afterwards, the protein-repelling property of the assemblies in model protein environments (BSA - bovine serum albumin, lysozyme and IgG - immunoglobulin G) was evaluated. We report that, regardless the morphology, PHPMA35-b-PDPA42 block copolymer assemblies are highly stable with negligible protein binding. On the other hand, PEOm-b-PLAn nanostructures are susceptible to protein adsorption and the phenomenon is protein-dependent. The nanoparticles are more susceptible to adsorption of the model positively charged biomacromolecule (lysozyme). The adsorption phenomenon is thermodynamically complex with simultaneous endothermic and exothermic processes involved. Although the experimental data highlight that qualitatively the morphology plays negligible effects on the event, fluorescence spectroscopy measurements evidenced that the binding is stronger onto the surface of nanoparticles stabilized by shorter hydrophilic shells. Nevertheless, the adsorption does not affect the secondary structure of the model proteins as confirmed by circular dichroism spectroscopy. Overall, by comparing soft nanoparticles stabilized by PEO and PHPMA, the latter is herein proved to be a better choice towards the manufacturing of non-fouling structures (either core-shell or hollow spheres) where even a reasonably short hydrophilic chain confers outstanding protein-repelling feature.

International audience; Emulsified systems are widely used for topical delivery with the aim of optimizing cutaneous absorption and offering a pleasant sensory. They also may provide a protection of the active molecule against oxidation and/or degradation. The oil phase of o/w emulsions may consist of liquid crystalline structures, especially lamellar structures which are similar to those found in the stratum corneum lipids. In the present work, o/w emulsions containing liquid crystals of mixed cetyl alcohol and Polysorbate 60 were developed for topical delivery of vitamin C, a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. In addition to the well-documented lipid supplementation of the stratum corneum, the liquid crystal emulsions provide a significant chemical stabilization of vitamin C against its degradation. Emulsions were characterized by X-ray diffraction, polarized optical 2 microscopy, and transmission electron microscopy. The stability of vitamin C in the formulations was evaluated upon storage in different conditions of temperature. The emulsions contain a complex colloidal structure, consisting of lamellar liquid crystalline (Lα) and crystalline lamellar gel (Lβ) phases, that provide a very efficient protection of vitamin C against its degradation.

Membrane fusion is a ubiquitous process in biology and is a prerequisite for many intracellular delivery protocols relying on the use of liposomes as drug carriers. Here, we investigate in detail the process of membrane fusion and the role of opposite charges in a protein-free lipid system based on cationic liposomes (LUVs) and anionic giant unilamellar vesicles (GUVs) composed of different palmitoyloleoylphosphatidylcholine:palmitoyloleoylphosphatidylglycerol (POPC:POPG) molar ratios. By using a set of optical microscopy- and microfluidics-based methods, we show that liposomes strongly dock to GUVs of pure POPC or low POPG fraction (up to 10 mol%), in a process mainly associated with hemifusion and membrane tension increase, commonly leading to GUV rupture. On the other hand, docked LUVs quickly and very efficiently fuse with negative GUVs of POPG fractions at or above 20 mol%, resulting in dramatic GUV area increase in a charged-dependent manner. Importantly, both hemifusion and full fusion are leakage-free. Fusion efficiency is quantified by the lipid transfer from liposomes to GUVs upon fusion using fluorescence resonance energy transfer (FRET), which leads to con-sistent results when compared to fluorescence lifetime-based FRET. We develop an approach to deduce the final composition of single GUVs after fusion based on the FRET efficiency. We can conclude that fusion is driven by membrane charge and appears to proceed up to charge-neutralization of the acceptor GUV.

Objective To investigate the relationships between exercise and incidence of congenital anomalies and hyperthermia. Design Systematic review with random-effects meta-analysis. Data sources Online databases were searched from inception up to 6 January 2017. Study eligibility criteria Studies of all designs were eligible (except case studies and reviews) if they were published in English, Spanish or French, and contained information on population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [e.g., dietary; "exercise + co-intervention"]), comparator (no exercise or different frequency, intensity, duration, volume or type of exercise) and outcome (maternal temperature and fetal anomalies). Results This systematic review and meta-analysis included 'very low' quality evidence from 14 studies (n=78 735) reporting on prenatal exercise and the odds of congenital anomalies, and 'very low' to 'low' quality evidence from 15 studies (n=447) reporting on maternal temperature response to prenatal exercise. Prenatal exercise did not increase the odds of congenital anomalies (OR 1.23, 95% CI 0.77 to 1.95, I-2=0%). A small but significant increase in maternal temperature was observed from pre-exercise to both during and immediately after exercise (during: 0.26 degrees C, 95% CI 0.12 to 0.40, I-2=70%; following: 0.24 degrees C, 95% CI 0.17 to 0.31, I-2=47%). Summary/Conclusions These data suggest that moderate-to-vigorous prenatal exercise does not induce hyperthermia or increase the odds of congenital anomalies. However, exercise responses were investigated in most studies after 12 weeks' gestation when the risk of de novo congenital anomalies is negligible.

Objective The purpose of this review was to investigate the relationship between prenatal exercise, and low back (LBP), pelvic girdle (PGP) and lumbopelvic (LBPP) pain. Design Systematic review with random effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were eligible (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [eg, dietary; "exercise + co-intervention"]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (prevalence and symptom severity of LBP, PGP and LBPP). Results The analyses included data from 32 studies (n=52 297 pregnant women). 'Very low' to 'moderate' quality evidence from 13 randomised controlled trials (RCTs) showed prenatal exercise did not reduce the odds of suffering from LBP, PGP and LBPP either in pregnancy or the postpartum period. However, 'very low' to 'moderate' quality evidence from 15 RCTs identified lower pain severity during pregnancy and the early postpartum period in women who exercised during pregnancy (standardised mean difference -1.03, 95% CI -1.58, -0.48) compared with those who did not exercise. These findings were supported by 'very low' quality evidence from other study designs. Conclusion Compared with not exercising, prenatal exercise decreased the severity of LBP, PGP or LBPP during and following pregnancy but did not decrease the odds of any of these conditions at any time point.

Objective To perform a systematic review of the relationship between prenatal exercise and fetal or newborn death. Design Systematic review with random-effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [eg, dietary; "exercise + co-intervention"]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (miscarriage or perinatal mortality). Results Forty-six studies (n=2 66 778) were included. There was 'very low' quality evidence suggesting no increased odds of miscarriage (23 studies, n=7125 women; OR 0.88, 95% CI 0.63 to 1.21, I-2=0%) or perinatal mortality (13 studies, n=6837 women, OR 0.86, 95% CI 0.49 to 1.52, I-2=0%) in pregnant women who exercised compared with those who did not. Stratification by subgroups did not affect odds of miscarriage or perinatal mortality. The meta-regressions identified no associations between volume, intensity or frequency of exercise and fetal or newborn death. As the majority of included studies examined the impact of moderate intensity exercise to a maximum duration of 60 min, we cannot comment on the effect of longer periods of exercise. Summary/conclusions Although the evidence in this field is of 'very low' quality, it suggests that prenatal exercise is not associated with increased odds of miscarriage or perinatal mortality. In plain terms, this suggests that generally speaking exercise is 'safe' with respect to miscarriage and perinatal mortality.

Objective To perform a systematic review of the relationships between prenatal exercise and maternal harms including labour/delivery outcomes. Design Systematic review with random effects meta-analysis and meta-regression. Datasources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise, alone ["exercise-only"] or in combination with other intervention components [e.g., dietary; "exercise + co-intervention"]) and outcome (preterm/prelabour rupture of membranes, caesarean section, instrumental delivery, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms (author defined) and diastasis recti). Results 113 studies (n=52 858 women) were included. 'Moderate' quality evidence from exercise-only randomised controlled trials (RCTs) indicated a 24% reduction in the odds of instrumental delivery in women who exercised compared with women who did not (20 RCTs, n=3819; OR 0.76, 95% CI 0.63 to 0.92, I (2)= 0 %). The remaining outcomes were not associated with exercise. Results from meta-regression did not identify a dose-response relationship between frequency, intensity, duration or volume of exercise and labour and delivery outcomes. Summary/conclusions Prenatal exercise reduced the odds of instrumental delivery in the general obstetrical population. There was no relationship between prenatal exercise and preterm/prelabour rupture of membranes, caesarean section, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms and diastasis recti.

Additional file 1. Peptide production.

Affinity chromatography (AC) has been used in large-scale bioprocessing for almost 40 years and is considered the preferred method for primary capture in downstream processing of various types of biopharmaceuticals. The objective of this mini-review is to provide an overview of a) the history of bioprocess AC, b) the current state of platform processes based on affinity capture steps, c) the maturing field of custom developed bioprocess affinity resins, d) the advantages of affinity capture-based downstream processing in comparison to other forms of chromatography, and e) the future direction for bioprocess scale AC. The use of AC can result in economic advantages by enabling the standardization of process development and the manufacturing processes and the use of continuous operations in flexible multiproduct production suites. These concepts are discussed from a growing field of custom affinity bioprocess resin perspective. The custom affinity resins not only address the need for a capture resin for non-platformable processes, but also can be employed in polishing applications, where they are used to define and control drug substance composition by separating specific product variants from the desired product form.

Objective To examine the influence of prenatal exercise on depression and anxiety during pregnancy and the postpartum period. Design Systematic review with random effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal depression or anxiety). Results A total of 52 studies (n=131406) were included. Moderate' quality evidence from randomised controlled trials (RCTs) revealed that exercise-only interventions, but not exercise+cointerventions, reduced the severity of prenatal depressive symptoms (13 RCTs, n=1076; standardised mean difference: -0.38, 95%CI -0.51 to -0.25, I-2=10%) and the odds of prenatal depression by 67% (5 RCTs, n=683; OR: 0.33, 95%CI 0.21 to 0.53, I-2=0%) compared with no exercise. Prenatal exercise did not alter the odds of postpartum depression or the severity of depressive symptoms, nor anxiety or anxiety symptoms during or following pregnancy. To achieve at least a moderate effect size in the reduction of the severity of prenatal depressive symptoms, pregnant women needed to accumulate at least 644 MET-min/week of exercise (eg, 150min of moderate intensity exercise, such as brisk walking, water aerobics, stationary cycling, resistance training). Summary/Conclusions Prenatal exercise reduced the odds and severity of prenatal depression.

Objective To examine the relationships between prenatal physical activity and prenatal and postnatal urinary incontinence (UI). Design Systematic review with random effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [e.g., dietary; exercise + co-intervention]), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal UI). Results 24 studies (n=15982 women) were included. Low' to moderate' quality evidence revealed prenatal pelvic floor muscle training (PFMT) with or without aerobic exercise decreased the odds of UI in pregnancy (15 randomised controlled trials (RCTs), n=2764 women; OR 0.50, 95% CI 0.37 to 0.68, I-2=60%) and in the postpartum period (10 RCTs, n=1682 women; OR 0.63, 95%CI 0.51, 0.79, I-2=0%). When we analysed the data by whether women were continent or incontinent prior to the intervention, exercise was beneficial at preventing the development of UI in women with continence, but not effective in treating UI in women with incontinence. There was low' quality evidence that prenatal exercise had a moderate effect in the reduction of UI symptom severity during (five RCTs, standard mean difference (SMD) -0.54, 95%CI -0.88 to -0.20, I-2=64%) and following pregnancy (three RCTs, moderate' quality evidence; SMD -0.54, 95% CI -0.87 to -0.22, I-2=24%). Conclusion Prenatal exercise including PFMT reduced the odds and symptom severity of prenatal and postnatal UI. This was the case for women who were continent before the intervention. Among women who were incontinent during pregnancy, exercise training was not therapeutic.

Acute increases in blood glucose are associated with heightened muscle sympathetic nerve activity (MSNA). Animal studies have implicated a role for peripheral chemoreceptors in this response, but this has not been examined in humans. Heart rate, cardiac output (CO), mean arterial pressure, total peripheral conductance, and blood glucose concentrations were collected in 11 participants. MSNA was recorded in a subset of 5 participants via microneurography. Participants came to the lab on 2 separate days (i.e., 1 control and 1 experimental day). On both days, participants ingested 75 g of glucose following baseline measurements. On the experimental day, participants breathed 100% oxygen for 3 min at baseline and again at 20, 40, and 60 min after glucose ingestion to deactivate peripheral chemoreceptors. Supplemental oxygen was not given to participants on the control day. There was a main effect of time on blood glucose (P < 0.001), heart rate (P < 0.001), CO (P < 0.001), sympathetic burst frequency (P < 0.001), burst incidence (P = 0.01), and total MSNA (P = 0.001) for both days. Blood glucose concentrations and burst frequency were positively correlated on the control day (r = 0.42; P = 0.03) and experimental day (r = 0.62; P = 0.003). There was a time × condition interaction (i.e., normoxia vs. hyperoxia) on burst frequency, in which hyperoxia significantly blunted burst frequency at 20 and 60 min after glucose ingestion only. Given that hyperoxia blunted burst frequency only during hyperglycemia, our results suggest that the peripheral chemoreceptors are involved in activating MSNA after glucose ingestion.

The effect of 5 mol%, 9 mol%, and 16 mol% of C24:1 β-glucosylceramide (βGlcCer) on the structure of cationic DODAB bilayers was investigated by means of differential scanning calorimetry (DSC), electron spin resonance (ESR) spectroscopy and fluorescence microscopy. βGlcCer is completely miscible with DODAB at all fractions tested, since no domains were observed in fluorescence microscopy or ESR spectra. The latter showed that βGlcCer destabilized the gel phase of DODAB bilayers by decreasing the gel phase packing. As a consequence, βGlcCer induced a decrease in the phase transition temperature and cooperativity of DODAB bilayers, as seen in DSC thermograms. ESR spectra also showed that βGlcCer induced an increase in DODAB fluid phase order and/or rigidity. Despite their different structures, a similar effect of loosening the gel phase packing and turning the fluid phase more rigid/organized has also been observed when low molar fractions of cholesterol were incorporated in DODAB bilayers. The structural characterization of mixed membranes made of cationic lipids and glucosylceramides may be important for developing novel immunotherapeutic tools such as vaccine adjuvants.

ObjectiveTo perform a systematic review and meta-analysis to explore the relationship between prenatal exercise and glycaemic control.DesignSystematic review with random-effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of acute or chronic exercise, alone (‘exercise-only’) or in combination with other intervention components (eg, dietary; ‘exercise+cointervention’) at any stage of pregnancy), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (glycaemic control).ResultsA total of 58 studies (n=8699) were included. There was ‘very low’ quality evidence showing that an acute bout of exercise was associated with a decrease in maternal blood glucose from before to during exercise (6 studies, n=123; mean difference (MD) −0.94 mmol/L, 95% CI −1.18 to −0.70, I2=41%) and following exercise (n=333; MD −0.57 mmol/L, 95% CI −0.72 to −0.41, I2=72%). Subgroup analysis showed that there were larger decreases in blood glucose following acute exercise in women with diabetes (n=26; MD −1.42, 95% CI −1.69 to −1.16, I2=8%) compared with those without diabetes (n=285; MD −0.46, 95% CI −0.60 to −0.32, I2=62%). Finally, chronic exercise-only interventions reduced fasting blood glucose compared with no exercise postintervention in women with diabetes (2 studies, n=70; MD −2.76, 95% CI −3.18 to −2.34, I2=52%; ‘low’ quality of evidence), but not in those without diabetes (9 studies, n=2174; MD −0.05, 95% CI −0.16 to 0.05, I2=79%).ConclusionAcute and chronic prenatal exercise reduced maternal circulating blood glucose concentrations, with a larger effect in women with diabetes.

ObjectiveWe aimed to identify the relationship between maternal prenatal exercise and birth complications, and neonatal and childhood morphometric, metabolic and developmental outcomes.DesignSystematic review with random-effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were eligible (except case studies and reviews) if published in English, Spanish or French, and contained information on the relevant population (pregnant women without contraindication to exercise), intervention (subjective/objective measures of frequency, intensity, duration, volume or type of exercise, alone (‘exercise-only’) or in combination with other intervention components (eg, dietary; ‘exercise+cointervention’)), comparator (no exercise or different frequency, intensity, duration, volume, type or trimester of exercise) and outcomes (preterm birth, gestational age at delivery, birth weight, low birth weight (4000 g), small for gestational age, large for gestational age, intrauterine growth restriction, neonatal hypoglycaemia, metabolic acidosis (cord blood pH, base excess), hyperbilirubinaemia, Apgar scores, neonatal intensive care unit admittance, shoulder dystocia, brachial plexus injury, neonatal body composition (per cent body fat, body weight, body mass index (BMI), ponderal index), childhood obesity (per cent body fat, body weight, BMI) and developmental milestones (including cognitive, psychosocial, motor skills)).ResultsA total of 135 studies (n=166 094) were included. There was ‘high’ quality evidence from exercise-only randomised controlled trials (RCTs) showing a 39% reduction in the odds of having a baby >4000 g (macrosomia: 15 RCTs, n=3670; OR 0.61, 95% CI 0.41 to 0.92) in women who exercised compared with women who did not exercise, without affecting the odds of growth-restricted, preterm or low birth weight babies. Prenatal exercise was not associated with the other neonatal or infant outcomes that were examined.ConclusionsPrenatal exercise is safe and beneficial for the fetus. Maternal exercise was associated with reduced odds of macrosomia (abnormally large babies) and was not associated with neonatal complications or adverse childhood outcomes.

Membrane fusion is a ubiquitous process in biology and is a prerequisite for many intracellular delivery protocols relying on the use of liposomes as drug carriers. Here, we investigate in detail the process of membrane fusion and the role of opposite charges in a protein-free lipid system based on cationic liposomes (LUVs, large unilamellar vesicles) and anionic giant unilamellar vesicles (GUVs) composed of different palmitoyloleoylphosphatidylcholine (POPC)/palmitoyloleoylphosphatidylglycerol (POPG) molar ratios. By using a set of optical-microscopy- and microfluidics-based methods, we show that liposomes strongly dock to GUVs of pure POPC or low POPG fraction (up to 10 mol%) in a process mainly associated with hemifusion and membrane tension increase, commonly leading to GUV rupture. On the other hand, docked LUVs quickly and very efficiently fuse with negative GUVs of POPG fractions at or above 20 mol%, resulting in dramatic GUV area increase in a charge-dependent manner; the vesicle area increase is deduced from GUV electrodeformation. Importantly, both hemifusion and full fusion are leakage-free. Fusion efficiency is quantified by the lipid transfer from liposomes to GUVs using fluorescence resonance energy transfer (FRET), which leads to consistent results when compared to fluorescence-lifetime-based FRET. We develop an approach to deduce the final composition of single GUVs after fusion based on the FRET efficiency. The results suggest that fusion is driven by membrane charge and appears to proceed up to charge neutralization of the acceptor GUV.

ObjectiveTo perform a systematic review of the relationship between prenatal exercise and fetal or newborn death.DesignSystematic review with random-effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (miscarriage or perinatal mortality).ResultsForty-six studies (n=2 66 778) were included. There was ‘very low’ quality evidence suggesting no increased odds of miscarriage (23 studies, n=7125 women; OR 0.88, 95% CI 0.63 to 1.21, I2=0%) or perinatal mortality (13 studies, n=6837 women, OR 0.86, 95% CI 0.49 to 1.52, I2=0%) in pregnant women who exercised compared with those who did not. Stratification by subgroups did not affect odds of miscarriage or perinatal mortality. The meta-regressions identified no associations between volume, intensity or frequency of exercise and fetal or newborn death. As the majority of included studies examined the impact of moderate intensity exercise to a maximum duration of 60 min, we cannot comment on the effect of longer periods of exercise.Summary/conclusionsAlthough the evidence in this field is of ‘very low’ quality, it suggests that prenatal exercise is not associated with increased odds of miscarriage or perinatal mortality. In plain terms, this suggests that generally speaking exercise is ‘safe’ with respect to miscarriage and perinatal mortality.

ObjectiveTo perform a systematic review of the relationships between prenatal exercise and maternal harms including labour/delivery outcomes.DesignSystematic review with random effects meta-analysis and meta-regression.DatasourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]) and outcome (preterm/prelabour rupture of membranes, caesarean section, instrumental delivery, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms (author defined) and diastasis recti).Results113 studies (n=52 858 women) were included. ‘Moderate’ quality evidence from exercise-only randomised controlled trials (RCTs) indicated a 24% reduction in the odds of instrumental delivery in women who exercised compared with women who did not (20 RCTs, n=3819; OR 0.76, 95% CI 0.63 to 0.92, I 2= 0 %). The remaining outcomes were not associated with exercise. Results from meta-regression did not identify a dose–response relationship between frequency, intensity, duration or volume of exercise and labour and delivery outcomes.Summary/conclusionsPrenatal exercise reduced the odds of instrumental delivery in the general obstetrical population. There was no relationship between prenatal exercise and preterm/prelabour rupture of membranes, caesarean section, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms and diastasis recti.

ObjectiveTo examine the influence of prenatal exercise on depression and anxiety during pregnancy and the postpartum period.DesignSystematic review with random effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal depression or anxiety).ResultsA total of 52 studies (n=131 406) were included. ‘Moderate’ quality evidence from randomised controlled trials (RCTs) revealed that exercise-only interventions, but not exercise+cointerventions, reduced the severity of prenatal depressive symptoms (13 RCTs, n=1076; standardised mean difference: −0.38, 95% CI −0.51 to –0.25, I2=10%) and the odds of prenatal depression by 67% (5 RCTs, n=683; OR: 0.33, 95% CI 0.21 to 0.53, I2=0%) compared with no exercise. Prenatal exercise did not alter the odds of postpartum depression or the severity of depressive symptoms, nor anxiety or anxiety symptoms during or following pregnancy. To achieve at least a moderate effect size in the reduction of the severity of prenatal depressive symptoms, pregnant women needed to accumulate at least 644 MET-min/week of exercise (eg, 150 min of moderate intensity exercise, such as brisk walking, water aerobics, stationary cycling, resistance training).Summary/ConclusionsPrenatal exercise reduced the odds and severity of prenatal depression.

ObjectiveGestational diabetes mellitus (GDM), gestational hypertension (GH) and pre-eclampsia (PE) are associated with short and long-term health issues for mother and child; prevention of these complications is critically important. This study aimed to perform a systematic review and meta-analysis of the relationships between prenatal exercise and GDM, GH and PE.DesignSystematic review with random effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcomes (GDM, GH, PE).ResultsA total of 106 studies (n=273 182) were included. ‘Moderate’ to ‘high’-quality evidence from randomised controlled trials revealed that exercise-only interventions, but not exercise+cointerventions, reduced odds of GDM (n=6934; OR 0.62, 95% CI 0.52 to 0.75), GH (n=5316; OR 0.61, 95% CI 0.43 to 0.85) and PE (n=3322; OR 0.59, 95% CI 0.37 to 0.9) compared with no exercise. To achieve at least a 25% reduction in the odds of developing GDM, PE and GH, pregnant women need to accumulate at least 600 MET-min/week of moderate-intensity exercise (eg, 140 min of brisk walking, water aerobics, stationary cycling or resistance training).Summary/conclusionsIn conclusion, exercise-only interventions were effective at lowering the odds of developing GDM, GH and PE.