The influence of participant characteristics on the relationship between cuff pressure and level of blood flow restriction

Purpose: Previous investigations to establish factors influencing the blood flow restriction (BFR) stimulus have determined cuff pressures required for complete arterial occlusion, which does not reflect the partial restriction prescribed for this training technique. This study aimed to establish characteristics that should be accounted for when prescribing cuff pressures required for partial BFR. Methods: Fifty participants were subjected to incremental blood flow restriction of the upper and lower limbs by proximal pneumatic cuff inflation. Popliteal and brachial artery diameter, blood velocity and blood flow was assessed with Doppler ultrasound. Height, body mass, limb circumference, muscle–bone cross-sectional area, adipose thickness (AT) and arterial blood pressure were measured and used in different models of hierarchical linear regression to predict the pressure at which 60 % BFR (partial occlusion) occurred. Results: Combined analysis revealed a difference in cuff pressures required to elicit 60 % BFR in the popliteal (111 ± 12 mmHg) and brachial arteries (101 ± 12 mmHg). MAP (r = 0.58) and AT (r = −0.45) were the largest independent determinants of lower and upper body partial occlusion pressures. However, greater variance was explained by upper and lower limb regression models composed of DBP and BMI (48 %), and arm AT and DBP (30 %), respectively. Conclusion: Limb circumference has limited impact on the cuff pressure required for partial blood flow restriction which is in contrast to its recognised relationship with complete arterial occlusion. The majority of the variance in partial occlusion pressure remains unexplained by the predictor variables assessed in the present study

Brachial artery characteristics and micro-vascular filtration capacity in rock climbers

Rock climbers perform repeated isometric forearm muscle contractions subjecting the vasculature to repeated ischaemia and distorted haemodynamic signals. This study investigated forearm vascular characteristics in rock climbers compared to healthy untrained controls. Eight climbers (CLIMB) (BMI; 22.3, s = 2.0 kg/m2, isometric handgrip strength; 46, s = 8 kg) were compared against eight untrained controls (CON) (BMI; 23.8, s = 2.6 kg/m2, isometric handgrip strength; 37, s = 9 kg). Brachial artery diameter and blood flow were measured, using Doppler ultrasound, at rest and following 5-mins ischaemia (peak diameter) and ischaemic exercise (maximal dilation) to calculate flow mediated dilation (FMD) and dilatory capacity (DC). Capillary filtration capacity was assessed using venous occlusion plethysmography. Resting (4.30, s = 0.26 vs. 3.79, s = 0.39 mm), peak (4.67, s = 0.31 vs. 4.12, s = 0.45 mm) and maximal (5.14, s = 0.42 vs. 4.35, s = 0.47 mm) diameters were greater (P < 0.05) in CLIMB than CON, respectively, despite no difference in FMD (9.2, s = 2.6 vs. 8.7, s = 2.9%). Peak reactive hyperaemic blood flow (1136, s = 504 vs. 651, s = 221 ml/min) and capillary filtration capacity (3.8, s = 0.9 vs. 5.2, s = 0.7 ml.min−1.mmHg−1.100 ml tissue−1 × 10−3) were greater (P < 0.05) in CLIMB compared to CON, respectively. Rock climbers exhibit structural vascular adaptation compared to untrained control participants but have similar vascular function. This may contribute to the enhanced ability of climbers to perform repeated isometric contractions

Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: A pooled analysis of individual patient data

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P \u3c 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

Anticoagulant rodenticides in red kites (Milvus milvus) in Britain in 2017 and 2018

Second generation anticoagulant rodenticides (SGARs) can be toxic to all mammals and birds. Various studies have shown that, in Britain, there is widespread exposure to SGARs in a diverse range of predatory mammals and birds, including red kites (Milvus milvus) which scavenge dead rats, a target species for rodent control. The Wildlife Incident Monitoring Scheme (WIIS) and the Predatory Bird Monitoring Scheme (PBMS) have shown that some mortalities result from this secondary exposure. In the present study, we analysed liver SGAR residues in 77 red kites that had been found dead in Britain in either 2017 or 2018. The carcasses were submitted to and necropsied by the Disease Risk Analysis and Health Surveillance (DRAHS) programme, the PBMS, the WIIS for England & Wales, the WIIS for Scotland and the Raptor Health Scotland study; the livers from the kites were subsequently analysed for SGAR residues. All the organisations are partners in the WILDCOMS network that promotes collaboration among surveillance schemes that monitor disease and contaminants in vertebrate wildlife. All of the 66 kites from England & Wales and 10 of the 11 red kites from Scotland had detectable liver residues of at least one SGAR. When considering the sample of kites as a whole, brodifacoum, difenacoum and bromadiolone were each detected in 73, 71 and 60 kites, respectively. Difethialone was found in 11 individuals while flocoumafen was detected in only one bird. Sum liver SGAR concentrations ranged between non-detected and 1218 ng/g wet wt. (arithmetic mean: 246 ng/g, median 154 ng/g). Post-mortem examinations indicated that 13 (16.8%) of red kites examined had internal haemorrhaging that was not associated with detectable trauma and had detectable liver SGAR concentrations. These birds had sum SGAR liver concentrations that ranged from 135 ng/g wet weight to 1218 ng/g wet weight. SGARs were considered a contributory cause of death in these cases. The stewardship scheme for anticoagulant rodenticides came fully into force in mid-2016 as re-registration of products for use in the UK was completed. A key aim is to reduce exposure of non-target wildlife to anticoagulant rodenticides but stewardship also aims to maintain efficacious rat control and so the number and density of AR-contaminated rats may remain unchanged. However, diligent searching, removal and safe disposal of poisoned rats, as promoted by stewardship, might be expected to reduce the availability of poisoned dead rats to red kites [and other scavengers] and thereby reduce the proportion of birds that are exposed and/or the magnitude of exposure. Concomitant with stewardship was a relaxation of the indoor use only restriction previously applied to brodifacoum, flocoumafen and difethialone, the three most acutely toxic SGARs. Any consequent increase in outdoor use of these three SGARs could increase the risk of secondary exposure in red kites. We therefore compared the data in the current report with that collected in 2015 and 2016 to determine if there was any evidence of a change in pattern or magnitude of exposure in red kites that might be connected to stewardship and/or change in usage restriction. The proportion of red kites exposed to SGARs in 2015 (90.6%), 2016 (89.6%) 2017 (96,4%) and 2018 (100%) was always 90% or more; the higher percentages in 2017 and 2018 were principally due to a greater proportion of birds from Scotland containing residues. Brodifacoum and difenacoum were the most prevalent compounds (89% of red kites across the four years for each compound) along with bromadiolone (75%). On average, there were residues of three different SGARs in each kite liver. There was no significant difference between years in liver sum (Σ) SGAR concentrations. We investigated if there was a change between years in the exposure of red kites to brodifacoum, flocoumafen and difethialone, the compounds for which indoor only usage restrictions were relaxed in 2016. To enable statistical analysis of data on residue prevalence, it was necessary to pool the data into two-year blocks. Data on presence/absence of detectable brodifacoum, flocoumafen or difethialone residues were therefore compared for 2015/16 (pre and year of implementation of change in usage restriction) and 2017/18 (post-change in usage restriction). The proportion of red kites with detectable residues was 82% (50 out of 61 red kites) in 2015/16 but significantly higher (95%; 73 out of 77 red kites) in 2017/18. However, there was also an increase [albeit not statistically significant] in the proportion of red kites with detectable liver difenacoum or bromadiolone residues (90% in 2015/16 vs. 97% in 2017/18). Therefore, these data may simply reflect an increase in the prevalence of exposure to SGARs generally rather than any effect of change in usage restriction. There was no difference between the four years in the summed magnitude of liver brodifacoum, difethialone and flocoumafen concentrations. The percentage of red kites examined that were diagnosed as birds in which SGARs were implicated as a contributory cause of death did not differ significantly between individual years nor show a significant trend across the years; the overall average across the four years was 22%. However, if data were pooled by pairs of years (2017/8 vs 2015/16), the proportion of red kites for which SGARs were implicated as a contributory cause of death was lower (18%) in 2017/18 than in 2015/16 (33%) for red kites from England & Wales. Our findings do not indicate that there has been any reduction in exposure in red kites to SGARs following implementation of stewardship, in terms of either the proportion of individuals exposed or the magnitude of residues detected. There is some evidence (depending upon the statistical approach used) that the proportion of red kites in which SGARs were implicated as a contributory mortality factor has decreased in more recent years. There was no clear evidence that relaxation of usage restrictions on brodifacoum, difethialone and flocoumafen has altered the pattern of residue accumulation in red kites to date

Exercise duration-matched interval and continuous sprint cycling induce similar increases in AMPK phosphorylation, PGC-1α and VEGF mRNA expression in trained individuals

Purpose: The effects of low-volume interval and continuous ‘all-out’ cycling, matched for total exercise duration, on mitochondrial and angiogenic cell signalling was investigated in trained individuals. Methods: In a repeated measures design, 8 trained males ((Formula presented.), 57 ± 7 ml kg−1 min−1) performed two cycling exercise protocols; interval (INT, 4 × 30 s maximal sprints interspersed by 4 min passive recovery) or continuous (CON, 2 min continuous maximal sprint). Muscle biopsies were obtained before, immediately after and 3 h post-exercise. Results: Total work was 53 % greater (P = 0.01) in INT compared to CON (71.2 ± 7.3 vs. 46.3 ± 2.7 kJ, respectively). Phosphorylation of AMPKThr172 increased by a similar magnitude (P = 0.347) immediately post INT and CON (1.6 ± 0.2 and 1.3 ± 0.3 fold, respectively; P = 0.011), before returning to resting values at 3 h post-exercise. mRNA expression of PGC-1α (7.1 ± 2.1 vs. 5.5 ± 1.8 fold; P = 0.007), VEGF (3.5 ± 1.2 vs. 4.3 ± 1.8 fold; P = 0.02) and HIF-1α (2.0 ± 0.5 vs. 1.5 ± 0.3 fold; P = 0.04) increased at 3 h post-exercise in response to INT and CON, respectively; the magnitude of which were not different between protocols. Conclusions: Despite differences in total work done, low-volume INT and CON ‘all-out’ cycling, matched for exercise duration, provides a similar stimulus for the induction of mitochondrial and angiogenic cell signalling pathways in trained skeletal muscle

Species of Bursaphelenchus Fuchs, 1937 (Nematoda: Parasitaphelenchidae) and other nematode genera associated with insects from Pinus pinaster in Portugal

Insects associated with maritime pine, Pinus pinaster, in Portugal were collected and screened for the presence of Bursaphelenchus species. Nematodes were identified using Internal Transcribed Spacers-Restriction Fragment Length Polymorphism (ITS-RFLP) analysis of dauer juveniles and morphological identification of adults that developed from dauer juveniles on fungal cultures or on cultures in pine wood segments at 26 C. Several associations are described: Bursaphelenchus teratospicularis and Bursaphelenchus sexdentati are associated with Orthotomicus erosus; Bursaphelenchus tusciae, B. sexdentati and/or Bursaphelenchus pinophilus with Hylurgus ligniperda and Bursaphelenchus hellenicus with Tomicus piniperda, Ips sexdentatus and H. ligniperda. An unidentified Bursaphelenchus species is vectored by Hylobius sp. The previously reported association of Bursaphelenchus xylophilus with Monochamus galloprovincialis was confirmed. The association of Bursaphelenchus leoni with Pityogenes sp. is not definitively established and needs further studies for clarification. Other nematode genera besides Bursaphelenchus were found to be associated with the insects sampled, including two different species of Ektaphelenchus, Parasitorhabditis sp., Parasitaphelenchus sp., Contortylenchus sp. and other unidentified nematodes. The Ektaphelenchus species found in O. erosus is morphologically similar to B. teratospicularis found in the same insect; adults of both the species are found in cocoon-like structures under the elytra of the insects. Introduction Approximately one third of the nematodes belonging to the order Aphelenchida Siddiqi, 1980 are associated with insects (Poinar, 1983). These nematodes establish a variety of associations with the insects, which may be described as commensalism, e.g. phoresy (to the benefit of the nematode but not affecting the insect), mutualism (both the organisms benefit) or parasitism (nematodes benefit at the expense of the insect) (Giblin-Davis, 2004). Most Bursaphelenchus Fuchs, 1937 species are mycetophagous, feeding on fungi in the galleries of bark beetles and thu

The acute angiogenic signalling response to low-load resistance exercise with blood flow restriction

This study investigated protein kinase activation and gene expression of angiogenic factors in response to low-load resistance exercise with or without blood flow restriction (BFR). In a repeated measures cross-over design, six males performed four sets of bilateral knee extension exercise at 20% 1RM (reps per set = 30:15:15:continued to fatigue) with BFR (110 mmHg) and without (CON). Muscle biopsies were obtained from the vastus lateralis before, 2 and 4 h post-exercise. mRNA expression was determined using real-time RT-PCR. Protein phosphorylation/expression was determined using Western blot. p38MAPK phosphorylation was greater (p = 0.05) at 2 h following BFR (1.3 ± 0.8) compared to CON (0.4 ± 0.3). AMPK phosphorylation remained unchanged. PGC-1α mRNA expression increased at 2 h (5.9 ± 1.3 vs. 2.1 ± 0.8; p = 0.03) and 4 h (3.2 ± 0.8 vs. 1.5 ± 0.4; p = 0.03) following BFR exercise with no change in CON. PGC-1α protein expression did not change following either exercise. BFR exercise enhanced mRNA expression of vascular endothelial growth factor (VEGF) at 2 h (5.2 ± 2.8 vs 1.7 ± 1.1; p = .02) and 4 h (6.8 ± 4.9 vs. 2.5 ± 2.7; p = .01) compared to CON. mRNA expression of VEGF-R2 and hypoxia-inducible factor 1α increased following BFR exercise but only eNOS were enhanced relative to CON. Matrix metalloproteinase-9 mRNA expression was not altered in response to either exercise. Acute low-load resistance exercise with BFR provides a targeted angiogenic response potentially mediated through enhanced ischaemic and shear stress stimuli

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients

Background Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. Methods This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. Results Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. Conclusions Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds

S. cerevisiae Srs2 helicase ensures normal recombination intermediate metabolism during meiosis and prevents accumulation of Rad51 aggregates

YesWe investigated the meiotic role of Srs2, a multi-functional DNA helicase/translocase that destabilises Rad51-DNA filaments and is thought to regulate strand invasion and prevent hyper-recombination during the mitotic cell cycle. We find that Srs2 activity is required for normal meiotic progression and spore viability. A significant fraction of srs2 mutant cells progress through both meiotic divisions without separating the bulk of their chromatin, although in such cells sister centromeres often separate. Undivided nuclei contain aggregates of Rad51 colocalised with the ssDNA-binding protein RPA, suggesting the presence of persistent single-strand DNA. Rad51 aggregate formation requires Spo11-induced DSBs, Rad51 strand-invasion activity and progression past the pachytene stage of meiosis, but not the DSB end-resection or the bias towards interhomologue strand invasion characteristic of normal meiosis. srs2 mutants also display altered meiotic recombination intermediate metabolism, revealed by defects in the formation of stable joint molecules. We suggest that Srs2, by limiting Rad51 accumulation on DNA, prevents the formation of aberrant recombination intermediates that otherwise would persist and interfere with normal chromosome segregation and nuclear division.Biotechnology and Biological Sciences Research Council (BB/K009346/1

Second generation anticoagulant rodenticide residues in red kites 2020

Second generation anticoagulant rodenticides (SGARs) can be toxic to all mammals and birds if consumed. Various studies have shown that, in Britain, there is widespread exposure to SGARs in a diverse range of predatory mammals and birds, including red kites (Milvus milvus) which scavenge dead rats, a target species for rodent control. The Wildlife Incident Investigation Scheme1 (WIIS) and the Predatory Bird Monitoring Scheme (PBMS) have shown that some mortalities result from this secondary exposure. In the present study, we analysed liver SGAR residues in 25 red kites that had been found dead in Britain in 2020. The carcasses were submitted to and necropsied by the Disease Risk Analysis and Health Surveillance (DRAHS) programme, the PBMS, the WIIS for England & Wales, the WIIS for Scotland and the Raptor Health Scotland study. All the organisations are partners in the WILDCOMS (Wildlife Disease & Contaminant Monitoring & Surveillance Network) network that promotes collaboration among surveillance schemes that monitor disease and contaminants in vertebrate wildlife in the UK. The UK Rodenticide Stewardship Regime began to come into force in mid-2016 as reregistration of products for use in the UK was approved by the HSE; full implementation of the scheme was in early 2018. The key aim of this stewardship initiative is to support competence among all SGAR users, a potential benefit of this may be the reduced exposure of non-target wildlife to anticoagulant rodenticides. However, the number and density of SGAR-contaminated rats may remain unchanged although diligent searching, removal and safe disposal of poisoned rats, as promoted by the stewardship regime, might be expected to reduce the availability of poisoned dead rats to red kites (and other scavengers) and thereby reduce the proportion of birds that are exposed and/or the magnitude of exposure. Concomitant with the stewardship scheme was a relaxation of the indoor-use-only-restriction previously applied to brodifacoum, flocoumafen and difethialone, the three most acutely toxic SGARs. Any consequent increase in outdoor use of these three SGARs could increase the risk of secondary exposure in red kites. We therefore compared the data in the current report with that collected in 2015 and 2016 to determine if there was any evidence of a change in pattern or magnitude of exposure in red kites that might be connected to stewardship and/or change in usage restriction. All but one of the 21 red kites from England & Wales and two of the four red kites from Scotland had detectable liver residues of at least one type of SGAR. When considering the sample of red kites as a whole, brodifacoum, difenacoum and bromadiolone were each detected in 21, 19 and 17 red kites, respectively. Difethialone was found in four individuals while flocoumafen was detected in one bird. The proportion of analysed red kites exposed to SGARs in 2015 (91%), 2016 (90%) 2017 (96%), 2018 (100%) 2019 (91%) and 2020 (88%) was similar at circa 88% or more; the higher percentages in 2017 and 2018 were principally due to a greater proportion of birds from Scotland containing residues than observe in other years. Difenacoum, brodifacoum, and bromodialone were the most prevalent compounds (detected in 86%, 85%, and 76% of red kites across the six years for each compound, respectively). On average, there were detectable residues of three different SGARs in each red kite liver likely demonstrating multiple exposures. Sum liver SGAR concentrations in birds from 2020 ranged between non-detectable and 1086 ng/g wet weight (arithmetic mean: 371 ng/g wet weight, median 307 ng/g wet weight). Necropsy examinations indicated that three (13%) of red kites examined had internal haemorrhaging that was not associated with detectable trauma and also had detectable liver SGAR concentrations. These birds had sum SGAR liver concentrations of 663, 905 and 1086 ng/g wet weight. SGARs were considered a contributory cause of death resulting from unspecified use in these cases. SGARs were a contributory cause of death in 17% of the red kite cases examined across all six years. Over the period 2015 to 2020, a reduction has been observed in the percentage of red kites examined that were diagnosed as birds in which SGARs were implicated as a contributory cause of death. However, given that the WIIS scheme specifically examines suspected poisoning incidents, it is likely that poisoned birds are over represented in this sample compared to the population as a whole in all six years. Due to these reasons, caution should be used when interpreting evident changes in mortality rates due to the sampling protocols used in this study that may lead to over reporting of mortality rates, and those rates being subject to variations in relative contribution of the WIIS and PBMS to each year’s sample. There was no statistically significant difference between years, irrespective of cause of death, in median summed SGAR residues, and no evidence that the magnitude of accumulated summed SGAR residues has changed consistently over time. Sum bromadiolone and difenacoum concentrations were lower in 2016 than 2015, however, there was no difference for sum brodifacoum, flocoumafen, and difethialone concentrations. Data on presence/absence of detectable brodifacoum, flocoumafen or difethialone residues were compared for 2015/16 and 2017/18/19/20. The proportion of red kites with detectable residues of these three SGARs was 82% in 2015/16 and similar proportions were observed in 2017/18/19/20 (86%). Similarly, there was no significant difference in the proportion of red kites with detectable liver difenacoum or bromadiolone residues (90% in 2015/16 vs. 93% in 2017/18/19/20). Since the implementation of the stewardship regime no difference in exposure pattern relating to active ingredient has been detected. Our findings do not indicate that there has been a broad scale change in exposure in red kites to SGARs following implementation of stewardship in terms of either the proportion of the sample exposed or the magnitude of sum SGARs residues detected. There is some evidence (depending upon the statistical approach used) that the proportion of red kites in which SGARs were implicated as a contributory mortality factor has decreased in more recent years. Alternative approaches to monitoring SGARs in red kites could be considered that analyses a random but representative sample, and as part of such a programme there may also be value in monitoring SGARs in the blood of tracked individuals. There was no clear evidence that relaxation of usage restrictions on brodifacoum, difethialone and flocoumafen has altered the pattern of residues for these compounds in red kites to date. However, data following full implementation of the rodenticide stewardship scheme is currently limited to four years