The effect of training with weightlifting catching or pulling derivatives on squat jump and countermovement jump force–time adaptations

The purpose of this study was to examine the changes in squat jump (SJ) and countermovement jump (CMJ) force−time curve characteristics following 10 weeks of training with either load-matched weightlifting catching (CATCH) or pulling derivatives (PULL) or pulling derivatives that included force- and velocity-specific loading (OL). Twenty-five resistance-trained men were randomly assigned to the CATCH, PULL, or OL groups. Participants completed a 10 week, group-specific training program. SJ and CMJ height, propulsion mean force, and propulsion time were compared at baseline and after 3, 7, and 10 weeks. In addition, time-normalized SJ and CMJ force−time curves were compared between baseline and after 10 weeks. No between-group differences were present for any of the examined variables, and only trivial to small changes existed within each group. The greatest improvements in SJ and CMJ height were produced by the OL and PULL groups, respectively, while only trivial changes were present for the CATCH group. These changes were underpinned by greater propulsion forces and reduced propulsion times. The OL group displayed significantly greater relative force during the SJ and CMJ compared to the PULL and CATCH groups, respectively. Training with weightlifting pulling derivatives may produce greater vertical jump adaptations compared to training with catching derivatives

Tuning structural relaxations, mechanical properties, and degradation timescale of PLLA during hydrolytic degradation by blending with PLCL-PEG

Poly-L-lactide (PLLA) is a popular choice for medical devices due to its bioresorbability and superior mechanical properties compared with other polymers. However, although PLLA has been investigated for use in bioresorbable cardiovascular stents, it presents application-specific limitations which hamper device therapies. These include low toughness and strength compared with metals used for this purpose, and slow degradation. Blending PLLA with novel polyethylene glycol functionalised poly(L-lactide-co-$\varepsilon$-caprolactone) (PLCL-PEG) materials has been investigated here to tailor the mechanical properties and degradation behaviour of PLLA. This exciting approach provides a foundation for a next generation of bioresorbable materials whose properties can be rapidly tuned. The degradation of PLLA was significantly accelerated by addition of PLCL-PEG. After 30 days of degradation, several structural changes were observed in the polymer blends, which were dependent on the level of PLCL-PEG addition. Blends with low PLCL-PEG content displayed enthalpy relaxation, resulting in embrittlement, while blends with high PLCL-PEG content displayed crystallisation, due to enhanced chain mobility brought on by chain scission, also causing embrittlement. Moderate PLCL-PEG additions (10% PLCL(70:30)-PEG and 20 - 30% PLCL(80:20)-PEG) stabilised the structure, reducing the extent of enthalpy relaxation and crystallisation and thus retaining ductility. Compositional optimisation identified a sweet spot for this blend strategy, whereby the ductility was enhanced while maintaining strength. Our results indicate that blending PLLA with PLCL-PEG provides an effective method of tuning the degradation timescale and mechanical properties of PLLA, and provides important new insight into the mechanisms of structural relaxations that occur during degradation, and strategies for regulating these.Lucideon Lt

Characterisation of peripheral and central components of the rat monoiodoacetate model of Osteoarthritis

OBJECTIVE: Pain is the main reason patients report Osteoarthritis (OA), yet current analgesics remain relatively ineffective. This study investigated both peripheral and central mechanisms that lead to the development of OA associated chronic pain. DESIGN: The monoiodoacetate (MIA) model of OA was investigated at early (2-6 days post injection) and late (>14 days post injection) time points. Pain-like behaviour and knee histology were assessed to understand the extent of pain due to cartilage degradation. Electrophysiological single-unit recordings were taken from spinal wide dynamic range (WDR) neurons to investigate Diffuse Noxious Inhibitory Controls (DNIC) as a marker of potential changes in descending controls. Immunohistochemistry was performed on dorsal root ganglion (DRG) neurons to assess any MIA induced neuronal damage. Furthermore, qPCR was used to measure levels of glia cells and cytokines in the dorsal horn. RESULTS: Both MIA groups develop pain-like behaviour but only late phase animals display extensive cartilage degradation. Early phase animals have a normally functioning DNIC system but there is a loss of DNIC in late phase animals. We found no evidence for neuronal damage caused by MIA in either group, yet an increase in IL-1β mRNA in the dorsal horn of late phase animals. CONCLUSION: The loss of DNIC in late phase MIA animals suggests an imbalance in inhibitory and facilitatory descending controls, and a rise in the mRNA expression of IL-1β mRNA suggest the development of central sensitisation. Therefore, the pain associated with OA in late phase animals may not be attributed to purely peripheral mechanisms

A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs

The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development of the favored monohydrate form. Inspired by crystal structure prediction, the search for neat polymorphs was expanded to an unusual range of experiments, including melt crystallization under pressure, to work around solvate formation and the thermal instability of the molecule. Ten polymorphs of galunisertib were found; however, the structure predicted to be the most stable has yet to be obtained. We present the crystal structures of all ten unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modeling techniques to produce a complete structure landscape and assess the risk of late-appearing, more stable polymorphs. The exceptional conformational polymorphism of this prolific solvate former invites further development of methods, computational and experimental, that are applicable to larger, flexible molecules with complex solid form landscapes

Contrasting Polymorphism of Related Small Molecule Drugs Correlated and Guided by the Computed Crystal Energy Landscape

Solid form screening and crystal structure prediction (CSP) calculations were carried out on two related molecules, 3-(4-(benzo[d]isoxazole-3-yl)piperazin-1-yl)-2,2-dimethylpropanoic acid (B5) and 3-(4-dibenzo[b,f][1,4]oxepin-11-yl-piperazin-1-yl)-2,2-dimethylpropanoic acid (DB7). Only one anhydrate form was crystallized for B5, whereas multiple solid forms, including three neat polymorphs, were found for DB7. The crystal structure of B5 is P21/n Z′ = 1 with intramolecular hydrogen bonding, whereas Forms I and II of DB7 are conformational polymorphs with distinct Z′ = 1 P1̅ structures and intermolecular hydrogen bonds. A disordered structure for Form III of DB7 is proposed, based on CSP-generated structures which gave a promising match to the X-ray powder diffraction and solid state NMR data for this metastable form. The differences in the hydrogen bonding and experimental solid form landscapes of the two molecules appear to arise from the dominance of the self-assembly of the benzoisoxazolepiperazinyl and dibenzoxepinylpiperazinyl fragments and the consequent inability to produce amorphous or solvate forms as intermediates for B5. There is a subtle balance between the intramolecular conformational energy and the intermolecular dispersion, electrostatic and polarization interactions apparent in the analysis of the computationally generated thermodynamically competitive structures, which makes their relative stability quite sensitive to the computational method used. The value of simultaneously exploring the computationally and experimentally generated solid form landscapes of molecules in pharmaceutical development is discussed

Adaptation strategy to mitigate the impact of climate change on water resources in arid and semi-arid regions : a case study

Climate change and drought phenomena impacts have become a growing concern for water resources engineers and policy makers, mainly in arid and semi-arid areas. This study aims to contribute to the development of a decision support tool to prepare water resources managers and planners for climate change adaptation. The Hydrologiska Byråns Vattenbalansavdelning (The Water Balance Department of the Hydrological Bureau) hydrologic model was used to define the boundary conditions for the reservoir capacity yield model comprising daily reservoir inflow from a representative example watershed with the size of 14,924 km2 into a reservoir with the capacity of 6.80 Gm3. The reservoir capacity yield model was used to simulate variability in climate change-induced differences in reservoir capacity needs and performance (operational probability of failure, resilience, and vulnerability). Owing to the future precipitation reduction and potential evapotranspiration increase during the worst case scenario (−40% precipitation and +30% potential evapotranspiration), substantial reductions in streamflow of between −56% and −58% are anticipated for the dry and wet seasons, respectively. Furthermore, model simulations recommend that as a result of future climatic conditions, the reservoir operational probability of failure would generally increase due to declined reservoir inflow. The study developed preparedness plans to combat the consequences of climate change and drought

Effects of variations in resistance training frequency on strength development in well-trained populations and implications for in-season athlete training : a systematic review and meta-analysis

In-season competition and tournaments for team sports can be both long and congested, with some sports competing up to three times per week. During these periods of time, athletes need to prepare technically, tactically and physically for the next fixture and the short duration between fixtures means that, in some cases, physical preparation ceases, or training focus moves to recovery as opposed to progressing adaptations. The aim of this review was to investigate the effect of training frequency on muscular strength to determine if a potential method to accommodate in-season resistance training, during busy training schedules, could be achieved by utilizing shorter more frequent training sessions across a training week. A literature search was conducted using the SPORTDiscus, Ovid, PubMed and Scopus databases. 2134 studies were identified prior to application of the following inclusion criteria: (1) maximal strength was assessed, (2) a minimum of two different training frequency groups were included, (3) participants were well trained, and finally (4) compound exercises were included within the training programmes. A Cochrane risk of bias assessment was applied to studies that performed randomized controlled trials and consistency of studies was analysed using I as a test of heterogeneity. Secondary analysis of studies included Hedges' g effect sizes (g) and between-study differences were estimated using a random-effects model. Inconsistency of effects between pre- and post-intervention was low within-group (I  = 0%), and moderate between-group (I  ≤ 73.95%). Risk of bias was also low based upon the Cochrane risk of bias assessment. Significant increases were observed overall for both upper (p ≤ 0.022) and lower (p ≤ 0.008) body strength, pre- to post-intervention, when all frequencies were assessed. A small effect was observed between training frequencies for upper (g ≤ 0.58) and lower body (g ≤ 0.45). Over a 6-12-week period, there are no clear differences in maximal strength development between training frequencies, in well-trained populations. Such observations may permit the potential for training to be manipulated around competition schedules and volume to be distributed across shorter, but more frequent training sessions within a micro-cycle rather than being condensed into 1-2 sessions per week, in effect, allowing for a micro-dosing of the strength stimuli

Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over : a randomised controlled trial

Background: Observational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline. Methods: The study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire. Results: For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units). Conclusion: The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.Peer reviewedPublisher PD

A molecular picture of the problems in ensuring structural purity of tazofelone

Almost twenty years after the crystal polymorphism of tazofelone was first studied at Lilly, the compound was revisited by calculating the crystal energy landscape and complementing the calculations with experimental work for calibration purposes. The crystal structure prediction study confirmed the stability of racemic form II (RCII) and showed that the racemic compound had greater potential for polymorphism than the single enantiomer. The seeding experiment that has previously been shown to produce a racemic solid solution (SS) correlates with the isostructurality between some low energy racemic structures and the enantiopure form. Other low energy structures have the same layer structure as both racemic polymorphs and the newly-discovered, but closely related, polymorph RCIII, which accounts for the difficulty in obtaining phase pure samples of the metastable RCI and RCIII and the problems of structural purity evidenced by streaked diffraction spots for RCI–III in the single crystal diffraction. This molecular picture of the problems in ensuring structural purity in the layer structure polymorphs of tazofelone not only explains the crystal dependent thermochemistry measurements of tazofelone, but also shows the value of combining a range of experimental and computational techniques to investigate the organic solid state