Comparing Acceleration and Change of Direction Ability Between Backpedal and Cross-over Run Techniques for Use in American Football.

ABSTRACT: Angelino, D, McCabe, TJG, and Earp, JE. Comparing acceleration and change of direction ability between backpedal and cross-over run techniques for use in American football. J Strength Cond Res 35(1): 47-55, 2021-In American football, defensive backs guard receivers using either cross-over (CO) run or backpedal (BP) techniques, but the efficacy of these techniques is unknown. The purpose of this study was to compare linear acceleration (LA) and change of direction (CoD) ability when using CO and BP. Collegiate football defensive backs participated in LA (n = 13) and CoD (n = 7) testing. During LA, subjects performed CO, BP, and forward sprints with split times taken between 0-3 and 3-5 yd and ground reaction forces recorded 0 and 3 yd from the start. During CoD testing, subjects performed the CO or BP for 3 yd and then were given a cue to sprint to a gate 5 yd away in 1 of 4 directions (downfield, midfield, sideline, or upfield). In LA, CO was faster than BP between 0-3 yd (Δ -0.20 ± 0.02 seconds, p = 0.000) and 3-5 yd (Δ -0.12 ± 0.02 seconds, p = 0.000). At the start of the movement, CO demonstrated greater propulsive forces (p = 0.017). However, 3 yd from the start, CO demonstrated greater propulsive forces and reduced braking forces (p = 0.000 & 0.003). In CoD, CO was faster than BP when running in the downfield (Δ 0.21 ± 0.05 seconds, p = 0.044) and lateral directions (Δ 0.21 ± 0.08 seconds, p = 0.035), but similar in the upfield direction (Δ 0.01 ± 0.08, p = 0.986). Our results indicate that CO is superior to BP in LA, CoD ability, and movement efficiency and support the use of CO for defensive backs.

Mental health and suicide in former professional soccer players.

INTRODUCTION: There is growing recognition of an association between contact sports participation and increased risk of neurodegenerative disease, including Alzheimer's disease and chronic traumatic encephalopathy. In addition to cognitive impairment, a range of mental health disorders and suicidality are proposed as diagnostic features of traumatic encephalopathy syndrome, the putative clinical syndrome associated with chronic traumatic encephalopathy. However, to date, epidemiological data on contact sport participation and mental health outcomes are limited. METHODS: For a cohort of former professional soccer players (n=7676) with known high neurodegenerative mortality and their matched general population controls (n=23 028), data on mental health outcomes were obtained by individual-level record linkage to national electronic records of hospital admissions and death certification. RESULTS: Compared with matched population controls, former professional soccer players showed lower risk of hospital admission for anxiety and stress related disorders, depression, drug use disorders, alcohol use disorders and bipolar and affective mood disorders. Among soccer players, there was no significant difference in risk of hospitalisation for mental health disorders between outfield players and goalkeepers. There was no significant difference in rate of death by suicide between soccer players and controls. CONCLUSIONS: Among a population of former professional soccer players with known high neurodegenerative disease mortality, hospital admissions for common mental health disorders were lower than population controls, with no difference in suicide. Our data provide support for the reappraisal of currently proposed diagnostic clinical criteria for traumatic encephalopathy syndrome, in particular the inclusion of mental health outcomes.

Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening.

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and ß with low nanomolar affinity and <20-fold selectivity for α over ß and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERß (compound 42; 170-fold selectivity).

Healable luminescent self-assembly supramolecular metallogels possessing lanthanide (Eu/Tb) dependent rheological and morphological properties.

Herein we present the use of lanthanide directed self-assembly formation (Ln(III) = Eu(III), Tb(III)) in the generation of luminescent supramolecular polymers, that when swelled with methanol give rise to self-healing supramolecular gels. These were analyzed by using luminescent and (1)H NMR titrations studies, allowing for the identification of the various species involved in the subsequent Ln(III)-gel formation. These highly luminescent gels could be mixed to give a variety of luminescent colors depending on their Eu(III):Tb(III) stoichiometric ratios. Imaging and rheological studies showed that these gels prepared using only Eu(III) or only Tb(III) have different morphological and rheological properties, that are also different from those determined upon forming gels by mixing of Eu(III) and Tb(III) gels. Hence, our results demonstrate for the first time the crucial role the lanthanide ions play in the supramolecular polymerization process, which is in principle a host-guest interaction, and consequently in the self-healing properties of the corresponding gels, which are dictated by the same host-guest interactions.

Synthesis, photophysical and cytotoxicity evaluations of DNA targeting agents based on 3-amino-1,8-naphthalimide derived Tröger's bases.

The synthesis and characterisation of five bis-1,8-naphthalimide containing Tröger's bases 1­5 formed from their corresponding 3-amino-1,8-naphthalimide precursors 6­10 is described. The photophysical investigations of 1­5 and 6­10 were carried out in several organic solvents as well as in water and as a function of pH using UV-Vis absorption and fluorescence spectroscopies. The DNA binding affinities of 1­5 in aqueous solution at pH 7.4 were also investigated using several UV-Vis absorption and fluorescence experiments by using calf thymus DNA (ct-DNA). These molecules exhibited significant DNA binding affinities; where large binding values (Kb) in the range of 10(6) M(−1) were determined, even in competitive media (50 mM and 160 mM NaCl at pH 7.4). Thermal denaturation measurements also showed that 1­5 significantly stabilised the DNA helix. Using linear and circular dichroism we further demonstrated that the DNA binding interaction occurs both by intercalation and by groove binding. The Tröger's bases were further shown to be rapidly taken up into cells using confocal fluorescence spectroscopy; and cytotoxic studies in HeLa and MCF-7 cells showed that most of the Tröger's bases were effective cytotoxic agents with EC50 values of between 1.1­12 µM and that all the active compounds induced programmed cell death by apoptosis, where up to 70% cellular death was observed after 24 h of incubation for 4.

Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid.

Multi-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ∼215 and ∼228 °C, while the glass transition temperatures of CHS-III and CS-III were ∼101 and ∼79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve noncongruently leading to high and sustainable drug solution concentrations in water at 25 and 37 °C, with the ciprofloxacin concentration of 58.8±1.18 mg/mL after 1 h of the experiment at 37 °C. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically relevant properties, including molecular, solid state, and solubility characteristics.

Development of fully and partially protected fucosyl donors for oligosaccharide synthesis.

The use of fully and partially tert-butyldimethylsilyl (TBDMS) protected fucose thioglycosides as glycosyl donors for oligosaccharide synthesis is described. Both the trisilyl- and disilyl-protected thioglycoside donors were prepared, and their reactivity under a range of activation conditions was investigated. Both silyl-protected donors were found to give good yields of the desired α products and the silyl protecting groups could be removed in the presence of unsaturated bonds. The disilyl-protected donor was found to behave as an efficient, partially protected glycosyl donor. The synthetic scope and limitations of these new donors is presented. Both donors were applied to the synthesis of a Lewis X trisaccharide displaying a propargyl group at the anomeric position. It was determined that the additional steric bulk of the TBDMS group inferred unusual reactivity on these fucosyl donors.

More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome.

Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues. This signature, termed CellDRIFT, increased with age across multiple tissues, distinguished tumor from normal tissue, was escalated in normal breast tissue from cancer patients, and was transiently reset upon reprogramming. In addition, within-person tissue differences were correlated with predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Our findings suggest that age-related replication may drive epigenetic changes in cells and could push them toward a more tumorigenic state.

Recognition and sensing of biologically relevant anions in alcohol and mixed alcohol-aqueous solutions using charge neutral cleft-like glycol-derived pyridyl-amidothiourea receptors.

In this paper, the synthesis and the spectroscopic investigation of new colorimetric receptors for anions 3-6, possessing a glycol chain at the 4-position of the pyridyl ring, and 1 and 2, which lack such a chain, and the X-ray crystal structure of 2 is presented. Structures 3-6 are able to bind to anions in competitive media, such as alcohol or in a mixture of methanol and water, where the anion recognition gives rise to changes in the absorption spectra, which is red-shifted, in 1:1 or 1:2 (sensor/anion) stoichiometry. The anion recognition for 1 and 2 was also investigated in organic solvents and in a 4:1 mixture of DMSO/H(2)O. The binding of 1 to anions such as acetate, phosphate, and fluoride was also evaluated using (1)H NMR in DMSO-d(6).

Study of E/Z isomerization in a series of novel non-ligand binding pocket androgen receptor antagonists.

We report the conformational analysis of a series of 3-hydroxy-N'-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure-activity relationship analysis.

Pyridin-2-yl guanidine derivatives: conformational control induced by intramolecular hydrogen-bonding interactions.

The synthesis and conformational analysis of a series of pyridin-2-yl guanidine derivatives using NMR, X-ray crystallography, and B3LYP/6-31+G** theoretical studies are reported. A remarkable difference was observed in the (1)H NMR spectra of the guanidinium salts as compared with their N,N'-di-Boc protected and neutral analogues. This difference corresponds to a 180° change in the dihedral angle between the guanidine/ium moiety and the pyridine ring in the salts as compared to the Boc-protected derivatives, a conclusion that was supported by theoretical studies, X-ray data, and NMR analysis. Moreover, our data sustain the existence of two intramolecular hydrogen-bonding systems: (i) between the pyridine N1 atom and the guanidinium protons in the salts and (ii) within the tert-butyl carbamate groups of the Boc-protected derivatives. To verify that the observed conformational control arises from these intramolecular interactions, a new series of N-Boc-N'-propyl-substituted pyridin-2-yl guanidines were also prepared and studied.

Self-assembly of hybrid organic-inorganic polyoxomolybdates: solid-state structures and investigation of formation and core rearrangements in solution.

We report here a facile synthetic and analytical approach that allows us to identify and characterize functionalized polyoxomolybdate clusters that form upon the partial reduction of Mo(VI) salts in the presence of organoarsonate ligands. We demonstrated that electrospray ionization mass spectrometry, in combination with X-ray crystallography, provides an extremely powerful tool, allowing us to exploit slight perturbations of the ligand structures for the preparation of a series of unprecedented cluster compounds. Redox-active transition metals that adopt cubane or related structures are of particular interest because of their resemblance to active sites of enzymes. Our investigations underline the stability of the hybrid compounds in solution, an essential requirement for potential applications as catalysts. Supplemental analyses include measurements of the magnetic properties, NMR, IR, UV/vis, and bond-valence-sum analyses. Our results highlight the possibility of exploring real-time growth reactions of polyoxometales that emerge in solution and transform to produce hybrid organic-inorganic polyoxometalate clusters.

Photochemical [2 + 2] cycloaddition reactions of 6-alkenyl-3-phenylcyclohex-2-en-1-ones: using biradical conformation control to account for exceptions to the "rule of five".

A series of 6-alkenyl-3-phenylcyclohex-2-enones has been synthesised and the structures of the products obtained from them on irradiation have been determined. The 6-propenyl compounds afforded a tricyclic 'parallel' [2 + 2] cycloaddition product and a bicyclic enone resulting from hydrogen abstraction in the biradical intermediate. The 6-butenyl and 6-pentenyl analogues gave 'crossed' cycloaddition products only. Although the regiochemistry of these cycloaddition reactions cannot be explained in terms of the 'rule of five', it is compatible with the concept of 'biradical conformation control' which is based on a consideration of the energy and structure of the possible 1,4-biradical intermediates.

Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones.

A series of azetidin-2-ones substituted at positions 1, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin-binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerisation that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the highest potency in human MCF-7 breast cancer cells with IC(50) values of 7 nM and 10nM, respectively, comparable to combretastatin A-4. Compounds from this series also exhibited potent activity in MDA-MB-231 breast cancer cells and in the NCI60 cell line panel. No significant toxicity was observed in normal murine breast epithelial cells. The presence of larger, bulkier groups at the 3-position, for example, 3-naphthyl derivative 21 and 3-benzothienyl derivative 26, resulted in relatively lower antiproliferative activity in the micromolar range. Tubulin-binding studies of 28 (IC(50)=1.37 µM) confirmed that the molecular target of this series of compounds is tubulin. These novel 3-(thienyl) ß-lactam antiproliferative agents are useful scaffolds for the development of tubulin-targeting drugs.

{4,6-Bis[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene)hydrazinyl]pyrimidine-κN,N',N''}dichloridomanganese(II).

In the title compound, [MnCl(2)(C(18)H(18)N(8))], the geometry around the Mn(II) centre is distorted square-pyramidal. In the crystal structure, mol-ecules pack via weak C-H⋯N and C-H⋯Cl inter-actions.

{4,6-Bis[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene-κN)hydrazinyl-κN]pyrimidine-κN}dichloridocopper(II) methanol disolvate monohydrate.

The title compound, [CuCl(2)(C(18)H(18)N(8))]·2CH(3)OH·H(2)O, contains a penta-coordinated Cu(II) atom bonded to the tridentate 4,6-bis-[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene)hydrazin-yl]pyrimidine ligand and two Cl atoms. The geometry around the Cu(II) atom is distorted square-pyramidal. The mol-ecules pack in the crystal structure via O-H⋯Cl, O-H⋯N, C-H⋯Cl and C-H⋯O hydrogen bonds, C-H⋯π and π-π inter-actions [centroid-centroid distances of the pyrimidine-pyridine and pyridine-pyridine inter-actions are 3.750 (3) and 3.850 (3) Å, respectively], forming sheet-like assemblies.

Narrative review of mental illness in cricket with recommendations for mental health support.

INTRODUCTION: Epidemiology reporting within the cricketing medical literature has emerged over the past 2 years, with a focus on physical injuries. Despite mental health in elite sport gaining increasing recognition, few studies have addressed mental health symptoms and disorders within cricket. Recently, cricketers have been prominent in the mainstream media describing their lived experiences of mental illness. As a result, some have withdrawn from competition and suggested there is an unmet need for mental health services within the sport. OBJECTIVES: (i) To appraise the existing evidence on mental health symptoms and disorders amongst cricketers. (ii) To provide guidance on shaping mental health research and services within cricket. DESIGN: A narrative review of the literature from inception of available databases until 26 July 2019, with analysis and recommendations. RESULTS: Five studies were included in this narrative review. Studies covered a range of mental health symptoms and disorders, including distress, anxiety, depression, sleep disturbance, suicide, adverse alcohol use, illicit drug use, eating disorders and bipolar disorder. Results indicated that cricketers are at high risk for distress, anxiety, depression and adverse alcohol use. When compared with the general population, cricketers are more likely to experience anxiety and depressive symptoms. Rates of suicide were proposed to be high for test cricketers. Overall, studies to date have been of low quality, demonstrating non-rigorous research methods. Some studies have relied on non-validated questionnaires to collect self-reported data on mental health symptoms and disorders, while others have presented biographical data obtained through searches of the media. CONCLUSIONS: The results of this narrative review highlight the lack of evidence underpinning mental health services for athletes within cricket. We suggest the following recommendations for future research and practice: (i) normalising mental health symptoms and disorders; (ii) working with and helping vulnerable demographic segments within the target population; (iii) designing and implementing early recognition systems of mental health symptoms and disorders; (iv) addressing the mental health needs of cricketers on a population basis.