Health and Lifestyle Factors and Dementia Risk Among Former Professional Soccer Players.

Importance: Elite-level contact sport participation is associated with increased dementia risk, which may be attributable to sport-related traumatic brain injury and repetitive head impact exposure. However, the contribution of wider, potentially modifiable dementia risk factors remains uncertain.

Objective: To explore the association of potentially modifiable dementia risk factors with dementia risk among former professional soccer players.

Computation of random time-shift distributions for stochastic population models.

Even in large systems, the effect of noise arising from when populations are initially small can persist to be measurable on the macroscale. A deterministic approximation to a stochastic model will fail to capture this effect, but it can be accurately approximated by including an additional random time-shift to the initial conditions. We present a efficient numerical method to compute this time-shift distribution for a large class of stochastic models.

Neuropsychiatric Side Effects After Lumbosacral Epidural Steroid Injections: A Prospective Cohort Study.

Background: The central nervous system contains steroid receptors, particularly in the hypothalamic and limbic systems. These systems are responsible for driving certain emotions in humans, especially stress, anxiety, motivation, energy levels, and mood. Thus, corticosteroids may precipitate patients to experience these emotions.

Electronic Cigarette (E-Cig) Use in the Chronic Pain Population.

Background: Since electronic cigarettes (E-Cigs) were introduced to the United States (US) in 2007 its use has increased. Like other tobacco products, E-Cigs too pose health risks. Studies have shown a correlation between pain and tobacco use, with the association being bidirectional.

Discovery of a novel series of selective macrocyclic PKCTheta inhibitors.

A series of macrocyclic PKCθ inhibitors based on a 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one hinge binder has been studied. Different aromatic and heteroaromatic substituents have been explored in order to optimize potency, isoform selectivity as well as DMPK properties. The importance of the length of the macrocyclic linker has also been analyzed.

Impact and Implications of the COVID-19 Pandemic on Urological Training.

Introduction: COVID-19 has forever impacted health care in the U.S. Changes to health and hospital policies led to disruptions to both patient care and medical training.

Neurodegenerative disease risk among former international rugby union players.

Background: Autopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population.

Lower limb injuries in an english professional football club: injury analysis and recommendations for prevention.

Background: Lower limb injuries constitute a problem in the sport of football. Our aim is to explore patterns and trends of lower limb injuries in an English professional football club.

Methods: This is a descriptive epidemiological study.

Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players.

Importance: Neurodegenerative disease mortality is higher among former professional soccer players than general population controls. However, the factors contributing to increased neurodegenerative disease mortality in this population remain uncertain.

Objective: To investigate the association of field position, professional career length, and playing era with risk of neurodegenerative disease among male former professional soccer players.

Heading in Football: Incidence, Biomechanical Characteristics and the Association with Acute Cognitive Function-A Three-Part Systematic Review.

Background: There is growing concern surrounding the role of repetitive sub-concussive head impacts, such as football heading, on brain health.

Objectives: Three questions were addressed while only considering studies that observed heading exposure directly: (1) how frequently does heading occur within football training and matches, (2) what are the biomechanical characteristics of heading, and (3) is cognitive function affected by heading?

Methods: This review followed the steps described in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Electronic databases including MEDLINE and SPORTDiscus were searched from the earliest entry to July 2020.

Medical care and first aid: an interassociation consensus framework for organised non-elite sport during the COVID-19 pandemic.

The cessation of amateur and recreational sport has had significant implications globally, impacting economic, social and health facets of population well-being. As a result, there is pressure to resume sport at all levels. The ongoing prevalence of SARS-CoV-2 and subsequent 'second waves' require urgent best practice guidelines to be developed to return recreational (non-elite) sports as quickly as possible while prioritising the well-being of the participants and support staff.

Interassociation consensus recommendations for pitch-side emergency care and personal protective equipment for elite sport during the COVID-19 pandemic.

The COVID-19 pandemic has necessitated many novel responses in healthcare including sport and exercise medicine. The cessation of elite sport almost globally has had significant economic implications and resulted in pressure to resume sport in very controlled conditions. This includes protecting pitch-side medical staff and players from infection.

Discovery of -(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases.

The clinical success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases.

Neurodegenerative Disease Mortality among Former Professional Soccer Players.

Background: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized.

Methods: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation.

Football's InfluencE on Lifelong health and Dementia risk (FIELD): protocol for a retrospective cohort study of former professional footballers.

Introduction: In the past decade, evidence has emerged suggesting a potential link between contact sport participation and increased risk of late neurodegenerative disease, in particular chronic traumatic encephalopathy. While there remains a lack of clear evidence to test the hypothesis that contact sport participation is linked to an increased incidence of dementia, there is growing public concern regarding the risk. There is, therefore, a pressing need for research to gain greater understanding of the potential risks involved in contact sports participation, and to contextualise these within holistic health benefits of sport.

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase.

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled.

Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation.

Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity.

Imidazopyridyl compounds as aldosterone synthase inhibitors.

The inhibition of aldosterone synthase (CYP11B2) may be an effective treatment of hypertension and heart failure, among other ailments. Previously reported benzimidazole CYP11B2 inhibitors led the way for bioisosteric imidazopyridines that are both potent and selective over CYP11B1.

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors.

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin.

Discovery of 1-(1H-Pyrazolo[4,3-c]pyridin-6-yl)urea Inhibitors of Extracellular Signal-Regulated Kinase (ERK) for the Treatment of Cancers.

The ERK/MAPK pathway plays a central role in the regulation of critical cellular processes and is activated in more than 30% of human cancers. Specific BRAF and MEK inhibitors have shown clinical efficacy in patients for the treatment of BRAF-mutant melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the ERK signal pathway.

Identification of N-(1H-pyrazol-4-yl)carboxamide inhibitors of interleukin-1 receptor associated kinase 4: Bicyclic core modifications.

IRAK4 plays a critical role in the IL-1R and TLR signalling, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of permeable N-(1H-pyrazol-4-yl)carboxamides was developed by introducing lipophilic bicyclic cores in place of the polar pyrazolopyrimidine core of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides. Replacement of the pyrazolo[1,5-a]pyrimidine core with the pyrrolo[2,1-f][1,2,4]triazine, the pyrrolo[1,2-b]pyridazine, and thieno[2,3-b]pyrazine cores guided by cLogD led to the identification of highly permeable IRAK4 inhibitors with excellent potency and kinase selectivity.

Data analysis and review of radiology services at Glasgow 2014 Commonwealth Games.

Background: Medical services at the Glasgow 2014 Commonwealth Games (CWG) were provided though a purpose-built medical polyclinic, which had a fully equipped radiology department along with other services, set up within the main Games Village. Data analysis of radiology services offered at CWG has not been published before.

Setting: Imaging services within the polyclinic, Athletes Village, Glasgow 2014 CWG.

Discovery of 5-Amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Inhibitors of IRAK4.

Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential signal transducer downstream of the IL-1R and TLR superfamily, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides was developed via sequential modifications to the 5-position of the pyrazolopyrimidine ring and the 3-position of the pyrazole ring. Replacement of substituents responsible for poor permeability and improvement of physical properties guided by cLogD led to the identification of IRAK4 inhibitors with excellent potency, kinase selectivity, and pharmacokinetic properties suitable for oral dosing.

Discovery of Benzimidazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys.

We report the discovery of a benzimidazole series of CYP11B2 inhibitors. Hit-to-lead and lead optimization studies identified compounds such as 32, which displays potent CYP11B2 inhibition, high selectivity versus related CYP targets, and good pharmacokinetic properties in rat and rhesus. In a rhesus pharmacodynamic model, 32 produces dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.