Assessment of Nucleobase Protomeric and Tautomeric States in Nucleic Acid Structures for Interaction Analysis and Structure-Based Ligand Design.

With increasing interest in RNA as a therapeutic and a potential target, the role of RNA structures has become more important. Even slight changes in nucleobases, such as modifications or protomeric and tautomeric states, can have a large impact on RNA structure and function, while local environments in turn affect protonation and tautomerization. In this work, the application of empirical tools for pKa and tautomer prediction for RNA modifications was elucidated and compared with ab initio quantum mechanics (QM) methods and expanded toward macromolecular RNA structures, where QM is no longer feasible. In this regard, the Protonate3D functionality within the molecular operating environment (MOE) was expanded for nucleobase protomer and tautomer predictions and applied to reported examples of altered protonation states depending on the local environment. Overall, observations of nonstandard protomers and tautomers were well reproduced, including structural C+G:C(A) and A+GG motifs, several mismatches, and protonation of adenosine or cytidine as the general acid in nucleolytic ribozymes. Special cases, such as cobalt hexamine-soaked complexes or the deprotonation of guanosine as the general base in nucleolytic ribozymes, proved to be challenging. The collected set of examples shall serve as a starting point for the development of further RNA protonation prediction tools, while the presented Protonate3D implementation already delivers reasonable protonation predictions for RNA and DNA macromolecules. For cases where higher accuracy is needed, like following catalytic pathways of ribozymes, incorporation of QM-based methods can build upon the Protonate3D-generated starting structures. Likewise, this protonation prediction can be used for structure-based RNA-ligand design approaches.

NnU-Net versus mesh growing algorithm as a tool for the robust and timely segmentation of neurosurgical 3D images in contrast-enhanced T1 MRI scans.

PURPOSE: This study evaluates the nnU-Net for segmenting brain, skin, tumors, and ventricles in contrast-enhanced T1 (T1CE) images, benchmarking it against an established mesh growing algorithm (MGA). METHODS: We used 67 retrospectively collected annotated single-center T1CE brain scans for training models for brain, skin, tumor, and ventricle segmentation. An additional 32 scans from two centers were used test performance compared to that of the MGA. The performance was measured using the Dice-Sørensen coefficient (DSC), intersection over union (IoU), 95th percentile Hausdorff distance (HD95), and average symmetric surface distance (ASSD) metrics, with time to segment also compared. RESULTS: The nnU-Net models significantly outperformed the MGA (p < 0.0125) with a median brain segmentation DSC of 0.971 [95CI: 0.945-0.979], skin: 0.997 [95CI: 0.984-0.999], tumor: 0.926 [95CI: 0.508-0.968], and ventricles: 0.910 [95CI: 0.812-0.968]. Compared to the MGA's median DSC for brain: 0.936 [95CI: 0.890, 0.958], skin: 0.991 [95CI: 0.964, 0.996], tumor: 0.723 [95CI: 0.000-0.926], and ventricles: 0.856 [95CI: 0.216-0.916]. NnU-Net performance between centers did not significantly differ except for the skin segmentations Additionally, the nnU-Net models were faster (mean: 1139 s [95CI: 685.0-1616]) than the MGA (mean: 2851 s [95CI: 1482-6246]). CONCLUSIONS: The nnU-Net is a fast, reliable tool for creating automatic deep learning-based segmentation pipelines, reducing the need for extensive manual tuning and iteration. The models are able to achieve this performance despite a modestly sized training set. The ability to create high-quality segmentations in a short timespan can prove invaluable in neurosurgical settings.

Effects of intensified training and tapering periods using different exercise modalities on judo-specific physical test performances.

This study investigated the effects of intensified training and tapering periods using different exercise modalities on judo athletes' physical fitness. Fifty-nine adolescent male and female judo athletes (age 15 ± 1 years) were randomly assigned to one of three experimental groups or one control group (CG). Experimental groups (kumi-kata [KG], uchi-komi [UG] and running [RG]) trained four times per week over four weeks of intensified training (in addition to their usual technical-tactical judo training; CG underwent only the usual training) followed by 12 days of tapering. The countermovement jump test (CMJ), isometric and dynamic judogi chin-up tests (JCT), uchi-komi speed test (UST), Special Judo Fitness Test (SJFT) and Judo Physical Fitness Test (JPFT) were administered before and after the intensified period and after tapering. The CMJ performance was superior in KG compared with UG, RG and CG. Isometric JCT performance was superior in KG compared with RG and CG. Regarding UST, performance was superior in UG compared with RG and CG. The same performance was superior with respect to the same groups considering pre-training to tapering change. The SJFT index did not differ between groups or time-points. The JPFT index increased after intensified and tapering periods compared with before training, with KG eliciting higher values compared with CG. Coaches and conditioning coaches could administer kumi-kata high-intensity interval training to enhance athletes' judo-specific physical fitness.

Validity and Reliability of a Light-Based Electronic Target for Testing Response Time in Fencers.

ABSTRACT: De Giorgio, A, Iuliano, E, Turner, A, Millevolte, C, Cular, D, Ardigò, LP, and Padulo, J. Validity and reliability of a light-based electronic target for testing response time in fencers. J Strength Cond Res 35(9): 2636-2644, 2021-Response time (RT) is a fencing fundamental sensorimotor skill. Therefore, the aim of the current study was to examine the efficacy of a light-based electronic target in fencers, designed to measure and train this entity. Ninety-five fencers (M = 53; F = 42) were tested in regard to their RT, using a light-based electronic target, for 3 different attack types: simple attack, the lunge, and an attack after a 1.5-m thrust. All subjects were divided into elite vs. novice fencers. Elite fencers had national and international rankings, and were again divided with regard to used weapon: épéeists (n = 32; M = 19; F = 13) and foilists (n = 30; M = 13; F = 17). Measurement was evaluated for validity/reliability, sensitivity/specificity, and correlation. Reliability was high for all attack types (intraclass correlation coefficient 0.94-0.96). Lower RTs were found in males for 2 attack types with good sensitivity (81-93%)/specificity (50-91%) for all attack types. Elite fencers responded faster than novice fencers for all attack types (p < 0.001), whereas elite males were faster than females for 2 attack types (p < 0.01). Lower RTs in females correlated with level for one attack type (r = 0.797, p < 0.05). In conclusion, the light-based electronic target system was found to be highly reliable and therefore could be used by fencing athletes as a further measure of performance.

Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial.

BACKGROUND AND PURPOSE: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. METHODS: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. RESULTS: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P=0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P=0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (P=0.36) or stroke (P=0.33). CONCLUSIONS: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

Intervertebral disc and endplate cell characterisation highlights annulus fibrosus cells as the most promising for tissue-specific disc degeneration therapy.

Degenerative processes of the intervertebral disc (IVD) and cartilaginous endplate lead to chronic spine pathologies. Several studies speculated on the intrinsic regenerative capacity of degenerated IVD related to the presence of local mesenchymal progenitors. However, a complete characterisation of the resident IVD cell populations, particularly that isolated from the endplate, is lacking. The purpose of the present study was to characterise the gene expression profiles of human nucleus pulposus (NPCs), annulus fibrosus (AFCs) and endplate (EPCs) cells, setting the basis for future studies aimed at identifying the most promising cells for regenerative purposes. Cells isolated from NP, AF and EP were analysed after in vitro expansion for their stemness ability, immunophenotype and gene profiles by large-scale microarray analysis. The three cell populations shared a similar clonogenic, adipogenic and osteogenic potential, as well as an immunophenotype with a pattern resembling that of mesenchymal stem cells. NPCs maintained the greatest chondrogenic potential and shared with EPCs the loss of proliferation capability during expansion. The largest number of selectively highly expressed stemness, chondrogenic/tissue-specific and surface genes was found in AFCs, thus representing the most promising source of tissue-specific expanded cells for the treatment of IVD degeneration.

Intervertebral disc and endplate cells response to IL-1ß inflammatory cell priming and identification of molecular targets of tissue degeneration.

Inflammation represents an important factor leading to metabolic imbalance within the intervertebral disc (IVD), conducive to degenerative changes. Therefore, a thorough knowledge of the IVD and endplate (EP) cell behaviour in such pathological environments is essential when designing regenerative therapeutic strategies. The present study aimed at assessing the molecular response of the IVD constitutive nucleus pulposus (NPCs)-, annulus fibrosus (AFCs)- and endplate (EPCs)-derived cells to interleukin (IL)-1ß treatment, through large-scale, high-throughput microarray and protein analysis, identifying the differentially expressed genes and released proteins. Overall, the inflammatory stimulus downregulated stemness genes while upregulating pro-inflammatory, pro-angiogenic and catabolic genes, including matrix metalloproteases, which were not balanced by a concomitant upregulation of their inhibitors. Upregulation of anti-inflammatory and anabolic tumour necrosis factor inducible gene 6 protein (TNFAIP6), of IL-1 receptor antagonist (IL-1Ra) (at gene and protein levels) and of trophic insulin-like growth factor 1 (IGF1) was also observed in all cell types; IGF1 particularly in AFCs. An overall inhibitory effect of tumour necrosis factor alpha (TNFα) signal was observed in all cell types; however, EPCs showed the strongest anti-inflammatory behaviour. AFCs and EPCs shared the ability to limit the activation of the signalling mediated by specific chemokines. AFCs showed a slightly senescent attitude, with a downregulation of genes related to DNA repair or pro-mitosis. Results allowed for the identification of specific molecular targets in IVD and EP cells that respond to an inflammatory environment. Such targets can be either silenced (when pathological targets) or stimulated to counteract the inflammation.

Dementia With Lewy Bodies: A Clinicopathologic Series of False-positive Cases.

Diagnosing dementia with Lewy bodies (DLB) is challenging as symptoms are heterogenous and not specific to the disease. Here we present a clinicopathologic series of false-positive DLB cases. Patients were enrolled retrospectively from the Netherlands Brain Bank when they met the clinical criteria of probable DLB, but with a pathologic diagnosis other than DLB or Parkinson's disease dementia. Twenty-two false-positive cases were selected. Alzheimer disease with or without copathology was the most common (64%) pathologic diagnosis. Other pathologic diagnoses, such as frontotemporal dementia, multiple-system atrophy, Creutzfeldt-Jakob disease, and autoimmune encephalitis, were also encountered. Atypical clinical signs for DLB were present in almost half of the cases and could be a trigger to consider other diagnoses than DLB. Additional diagnostic examinations, feedback of pathologic diagnosis, and the creation of a set of clinical features that are indicative of other conditions, could reduce the amount of false-positive DLB cases.

Acinic cell carcinoma of the parotid gland: from pathogenesis to management: a literature review.

PURPOSE: Acinic cell carcinoma (ACCs) is uncommon malignant epithelial neoplasm of the salivary glands; the most common presentation is a well-defined painless solid mass. Diagnosis of ACCs is frequently complicated, due to its similarity with benign tumors. METHODS: A review of the literature available on ACCs was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. RESULTS: There are no clear characteristics of ACCs found on CT, MRI and ultrasound imaging. The management of the ACC, a rare malignancy of the parotid gland, is often difficult and controversial. Radical surgery is the best treatment option. The role of radiotherapy remains controversial: the precise indications and oncologic effects of adjuvant radiotherapy in ACC of the parotid gland are not well known. There is insufficient literature regarding the chemotherapy for metastatic ACC. CONCLUSION: Knowledge about ACC, a rare malignancy of parotid gland, has changed over the past few decades. More clinical randomized works would be needed, both to assess the real effectiveness of radio and chemotherapy and to have an unanimous consensus about their indications.

A Single Point Mutation in the Rhinovirus 2B Protein Reduces the Requirement for Phosphatidylinositol 4-Kinase Class III Beta in Viral Replication.

Rhinoviruses (RVs) replicate on cytoplasmic membranes derived from the Golgi apparatus. They encode membrane-targeted proteins 2B, 2C, and 3A, which control trafficking and lipid composition of the replication membrane. The virus recruits host factors for replication, such as phosphatidylinositol 4 (PI4)-kinase 3beta (PI4K3b), which boosts PI4-phosphate (PI4P) levels and drives lipid countercurrent exchange of PI4P against cholesterol at endoplasmic reticulum-Golgi membrane contact sites through the lipid shuttling protein oxysterol binding protein 1 (OSBP1). We identified a PI4K3b inhibitor-resistant RV-A16 variant with a single point mutation in the conserved 2B protein near the cytosolic carboxy terminus, isoleucine 92 to threonine (termed 2B[I92T]). The mutation did not confer resistance to cholesterol-sequestering compounds or OSBP1 inhibition, suggesting invariant dependency on the PI4P/cholesterol lipid countercurrents. In the presence of PI4K3b inhibitor, Golgi reorganization and PI4P lipid induction occurred in RV-A16 2B[I92] but not in wild-type infection. The knockout of PI4K3b abolished the replication of both the 2B[I92T] mutant and the wild type. Doxycycline-inducible expression of PI4K3b in PI4K3b knockout cells efficiently rescued the 2B[I92T] mutant and, less effectively, wild-type virus infection. Ectopic expression of 2B[I92T] or 2B was less efficient than that of 3A in recruiting PI4K3b to perinuclear membranes, suggesting a supportive rather than decisive role of 2B in recruiting PI4K3b. The data suggest that 2B tunes the recruitment of PI4K3b to the replication membrane and allows the virus to adapt to cells with low levels of PI4K3b while still maintaining the PI4P/cholesterol countercurrent for establishing Golgi-derived RV replication membranes.IMPORTANCE Human rhinoviruses (RVs) are the major cause of the common cold worldwide. They cause asthmatic exacerbations and chronic obstructive pulmonary disease. Despite recent advances, the development of antivirals and vaccines has proven difficult due to the high number and variability of RV types. The identification of critical host factors and their interactions with viral proteins and membrane lipids for the establishment of viral replication is a basis for drug development strategies. Our findings here shed new light on the interactions between nonstructural viral membrane proteins and class III phosphatidylinositol 4 kinases from the host and highlight the importance of phosphatidylinositol 4 phosphate for RV replication.

Nanostructured Catalysts for Dry-Reforming of Methane.

The manuscript deals on the main progress achieved by global scientific research on the development of nanostructured catalysts for dry-reforming reaction. The importance to have a global vision on this topic is strictly related to the most currently and important challenges in the sustainable energy production. In fact, dry-reforming is one of the few known processes in which greenhouse gases are utilized as reactants (methane and carbon dioxide) to produce syngas. Syngas represents the basis for liquid fuel production by Fischer-Tropsch process. In this broad and current context, the catalyst development plays a pivotal role due to its great influence on efficiency, and therefore on the costs, of the whole process. Several are the aspects to consider during the catalyst design: role of metal, interaction between metal and support, role of promoters and resistance to the coke deactivation. These issues, as well as the thermodynamics of the process, are the main aspects of which this review speaks about.

Validity and reliability of a standalone low-end 50-Hz GNSS receiver during running.

The aim of the investigation was to verify the validity and reliability of a low-end 50-Hz Global Navigation Satellite System receiver (GNSSr) for different soccer-specific run distances and average speed assessments. Six soccer players were assessed on two different days while performing eight different running paths with changes of direction for a final total of 44 runs. During the runs, each participant was equipped with the GNSSr, while the time for each single run was recorded using a photocell gate. Reference vs. receiver assessment correspondences for distance and average speed were evaluated by calculating the standard error of the estimate (SEE), coefficient of variation (CV), and mean bias. Residual vs. predicted value comparison was performed by means of Bland-Altman plots. Finally, calculating the intra-class correlations coefficient (ICC) assessed the test-retest reliability of the measurement. Receiver distance assessment showed an SEE of 0.52 m (0.73%), and mean bias of 0.06 m. Receiver average speed assessment showed an SEE of 0.02 m·s-1 (0.74%) and mean bias of 0.001 m·s-1. The Bland-Altman plot showed a small difference between the two assessments with the 95% limits of agreement=±1.08 m/0.046 m·s-1. Receiver distance/speed assessment was found to be reliable, with ICC=0.999. In spite of its low cost, the new low-end GNSSr provides valid and reliable assessments of distance and average speed for young adults performing several standardized running actions of differing lengths within delimited setup spaces.

Vibration effect on ball score test in international vs. national level table tennis.

In table tennis, motor skills are crucial for discriminating player level. However, there is a dearth of studies exploring the impact of a vibrational stimulus on performance. Thirty-four male players (age 25±2 years; body mass index, BMI 23.4±1.2 kg·m -2 ) participated in the study. Seventeen played at international level (IL), while the remaining 17 played at national level (NL). The participants underwent a ball-handling test, the ball score, before (PRE) and after (POST) a vibrational stimulus. Intra-class correlation (ICC) for the ball score result showed good reliability (ICC 0.87 for IL and 0.80 for NL). Repeated measures ANOVA showed differences between groups for ball score (p=0.000) and a significant group×time interaction (p=0.004). Better performances were observed for the IL group than for the NL group, significantly only for POST. Vibration produced positive and negative effects in IL and NL groups, respectively.

Can a Repeated Sprint Ability Test Help Clear a Previously Injured Soccer Player for Fully Functional Return to Activity? A Pilot Study.

OBJECTIVE: To investigate the effects of fatigue induced by a repeated sprint ability (RSA) test on the neuromuscular responses of soccer players with a recent history of lower limb injuries (CH) and a matched control group in good fitness condition (GH). DESIGN: This was a case-control study. PARTICIPANTS: Nine CH and 9 GH. INDEPENDENT VARIABLE: Allocation to CH or GH. MAIN OUTCOME MEASURES: Each player was assessed for blood lactate concentration and jumping performance [squat jump (SJ) and countermovement jump (CMJ)] before/after RSA. Post-RSA rate of perceived exertion (RPE) was obtained. Receiver operating characteristic analysis was performed to calculate RSA sensitivity and specificity in distinguishing between CH and GH. Intraclass correlation coefficient was used to assess reliability. RESULTS: No baseline differences were found for any variable. ΔSJ before/after RSA was -14 ± 2% and -5 ± 2% in CH and GH, respectively (P < 0.05). ΔCMJ before/after RSA was -15 ± 2% and -7 ± 2% in CH and GH, respectively (P < 0.05). ΔSJ-based and ΔCMJ-based (before/after RSA) area under curve (AUC) resulted in 0.90 ± 0.07 and 0.86 ± 0.09, respectively, with both AUCs differentiating between CH and GH with 77.78% sensitivity and 88.89% specificity. Pooled AUC resulted in 0.88 ± 0.06. Intraclass correlation coefficient was high (0.85/0.97). CONCLUSIONS: Repeated sprint ability is a simple, low-cost field test potentially able to assist in clinical decision making for return to sport.

Performance and Metabolic Demand of a New Repeated-Sprint Ability Test in Basketball Players: Does the Number of Changes of Direction Matter?

Zagatto, AM, Ardigò, LP, Barbieri, FA, Milioni, F, Dello Iacono, A, Camargo, BHF, and Padulo, J. Performance and metabolic demand of a new repeated-sprint ability test in basketball players: does the number of changes of direction matter? J Strength Cond Res 31(9): 2438-2446, 2017-This study compared 2 repeated-sprint ability (RSA) tests in basketball players. Both tests included 10 × 30-m sprints, with the difference that the previously validated test (RSA2COD) featured 2 changes of direction (COD) per sprint, whereas the experimental test (RSA5COD) featured 5 CODs per sprint. Test performances and metabolic demands were specifically assessed in 20 basketball players. First, RSA5COD test-retest reliability was investigated. Then, RSA2COD, RSA5COD sprint times, peak speeds, oxygen uptake (V[Combining Dot Above]O2) and posttest blood lactate concentration [La] were measured. The RSA5COD results showed to be reliable. RSA2COD performance resulted better than the RSA5COD version (p < 0.01), with shorter sprint times and higher peak speeds. Over sprints, the tests did not differ from each other in terms of V[Combining Dot Above]O2 (p > 0.05). Over whole bout, the RSA2COD was more demanding than the RSA5COD, considering overall metabolic power requirement (i.e., VO2-driven + [La]-driven components). Given that RSA5COD (a) mimics real game-play as sprint distance and action change frequency/direction and (b) has the same metabolic expenditure per task completion as metabolic cost, RSA5COD is a valuable option for players and coaches for training basketball-specific agility and assessing bioenergetic demands.

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

BACKGROUND: Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. AIM: We compared targeted versus universal screening of CRCs for Lynch syndrome. METHODS: In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. RESULTS: Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. CONCLUSIONS: In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Effect of Small-Sided Games and Repeated Shuffle Sprint Training on Physical Performance in Elite Handball Players.

This study was designed to compare the effects of small-sided games (SSGs) and repeated shuffle sprint (RSS) training on repeated sprint ability (RSA) and countermovement jump (CMJ) tests performances of elite handball players. Eighteen highly trained players (24.8 ± 4.4 years) were assigned to either SSG or RSS group training protocols twice a week for 8 weeks. The SSG training consisted of 5 small-sided handball games with 3-a-side teams excluding goalkeepers. The RSS consisted of 2 sets of 14-17 of 20-m shuttle sprints and 9-m jump shots interspersed by 20-second recoveries. Before and after training, the following performance variables were assessed: speed on 10-m and 20-m sprint time, agility and RSA time, CMJ height, standing throw, and jump shot speed. Significant pre-to-post treatment improvements were found in all the assessed variables following both training protocols (multivariate analysis of variance, p ≤ 0.05). There was a significantly greater improvement on 10-m sprint, CMJ, and jump shooting, after the RSS in comparison with SSG training (+4.4% vs. +2.4%, +8.6% vs. +5.6%, and +5.5% vs. +2.7%, respectively). Conversely, agility and standing throwing showed lower improvements after RSS in comparison with SSG (+1.0% vs. +7.8% and +1.6% vs. +9.0%, respectively). These results indicate that these training methods are effective for fitness development among elite adult handball players during the last period of the competitive season. Specifically, SSG seems to be more effective in improving agility and standing throw, whereas RSS seems preferable in improving 10-m sprint, CMJ, and jump shot.

Plant defences against ants provide a pathway to social parasitism in butterflies.

Understanding the chemical cues and gene expressions that mediate herbivore-host-plant and parasite-host interactions can elucidate the ecological costs and benefits accruing to different partners in tight-knit community modules, and may reveal unexpected complexities. We investigated the exploitation of sequential hosts by the phytophagous-predaceous butterfly Maculinea arion, whose larvae initially feed on Origanum vulgare flowerheads before switching to parasitize Myrmica ant colonies for their main period of growth. Gravid female butterflies were attracted to Origanum plants that emitted high levels of the monoterpenoid volatile carvacrol, a condition that occurred when ants disturbed their roots: we also found that Origanum expressed four genes involved in monoterpene formation when ants were present, accompanied by a significant induction of jasmonates. When exposed to carvacrol, Myrmica workers upregulated five genes whose products bind and detoxify this biocide, and their colonies were more tolerant of it than other common ant genera, consistent with an observed ability to occupy the competitor-free spaces surrounding Origanum. A cost is potential colony destruction by Ma. arion, which in turn may benefit infested Origanum plants by relieving their roots of further damage. Our results suggest a new pathway, whereby social parasites can detect successive resources by employing plant volatiles to simultaneously select their initial plant food and a suitable sequential host.

Six and 12 Weeks of Caloric Restriction Increases ß Cell Function and Lowers Fasting and Postprandial Glucose Concentrations in People with Type 2 Diabetes.

BACKGROUND: Caloric restriction alone has been shown to improve insulin action and fasting glucose metabolism; however, the mechanism by which this occurs remains uncertain. OBJECTIVE: We sought to quantify the effect of caloric restriction on ß cell function and glucose metabolism in people with type 2 diabetes. METHODS: Nine subjects (2 men, 7 women) with type 2 diabetes [BMI (in kg/m(2)): 40.6 ± 1.4; age: 58 ± 3 y; glycated hemoglobin: 6.9% ± 0.2%] were studied using a triple-tracer mixed meal after withdrawal of oral diabetes therapy. The oral minimal model was used to measure ß cell function. Caloric restriction limited subjects to a pureed diet (<900 kcal/d) for the 12 wk of study. The studies were repeated after 6 and 12 wk of caloric restriction. RESULTS: Fasting glucose concentrations decreased significantly from baseline after 6 wk of caloric restriction with no further reduction after a further 6 wk of caloric restriction (9.8 ± 1.3, 5.9 ± 0.2, and 6.2 ± 0.3 mmol/L at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01) because of decreased fasting endogenous glucose production (EGP: 20.4 ± 1.1, 16.2 ± 0.8, and 17.4 ± 1.1 µmol · kg(-1) · min(-1) at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.03). These changes were accompanied by an improvement in ß cell function measured by the disposition index (189 ± 51, 436 ± 68, and 449 ± 67 10(-14) dL · kg(-1) · min(-2) · pmol(-1) at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01). CONCLUSIONS: Six weeks of caloric restriction lowers fasting glucose and EGP with accompanying improvements in ß cell function in people with type 2 diabetes. An additional 6 wk of caloric restriction maintained the improvement in glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01094054.

An exploratory study of respiratory muscle endurance training in high lesion level paraplegic handbike athletes.

OBJECTIVE: To investigate the impact of respiratory muscle endurance training (RMET) on lung function and exercise performance in athletes with high lesion level paraplegia. DESIGN: This was a case-control intervention study. SETTING: Sport and exercise science laboratories and bike path. PARTICIPANTS: Twelve competitive handbike athletes with high lesion level paraplegia matched by lesion and fitness level in training (T) group (7) and control (C) group (5). INTERVENTIONS: The T group performed 20 RMET training sessions over a 4-week period using a SpiroTiger. Each session lasted for 30 minutes. The C group did not perform any RMET. MAIN OUTCOME MEASURES: Resting lung function, respiratory muscle endurance, and exercise performance (arm cranking maximal incremental test and simulated handbike time trial). RESULTS: Resting lung function was not different between groups and did not change with the intervention. After RMET, the respiratory muscle endurance was significantly increased by 27% in the T group but did not alter in the C group. Final minute ventilation was increased from 89 ± 20 L/min to 112 ± 20 L/min after RMET in the T group and the sensation of dyspnea decreased (P < 0.05). Peak oxygen consumption, peak mechanical power output, and handbike time trial performance were not different between groups and did not change with the RMET intervention. CONCLUSIONS: A short-term RMET intervention in handbike athletes with high lesion level paraplegia improved respiratory muscle endurance but had little impact on overall exercise performance.