Injuries in youth football: a prospective observational cohort analysis among players aged 9 to 13 years

OBJECTIVE: To determine the risk of injury in youth football games. SUBJECTS AND METHODS: Nine hundred fifteen players aged 9 to 13 years on 42 teams participated, including 10 teams in each grade from grades 4 through 6 and 6 teams each in grades 7 and 8. The study was conducted in the fall of 1997. Injury incidence, prevalence, and severity were calculated for each grade level and player position. Additional analyses examined the number of injuries according to body weight. RESULTS: A total of 55 injuries occurred in games during the entire season (overall prevalence, 5.97%). Most injuries were mild, and the most common type was contusion, which occurred in 33 players (60%). Four injuries (7%) were severe enough to prevent players from participating for the rest of the season. All 4 severe injuries were fractures involving the ankle physis. The risk of injury increased as players matured in age and grade level. Injury risk for an eighth-grade player was 4 times greater than the risk of injury to a fourth-grade player. A trend was identified for heavier players to be at increased risk, but no significant correlation was evident between body weight and injury. CONCLUSION: Our prospective observational analysis showed that most youth football injuries are mild. Older and heavier players appear to be at higher risk.     

Reverse vaccinology approach to design a multi-epitope vaccine construct based on the Mycobacterium tuberculosis biomarker PE_PGRS17

Mycobacterium tuberculosis (Mtb) is responsible for high mortality rates in many low- and middle-income countries. This infectious disease remains accountable for around 1.4 million deaths yearly. Finding effective control measures against Mtb has become imperative. Vaccination has been regarded as the safe and lasting control measure to curtail the impact of Mtb. This study used the Mtb protein biomarker PE_PGRS17 to design a multi-epitope vaccine. A previous study predicted a strong antigenic property of PE_PGRS17. Immunogenic properties such as antigenicity, toxicity, and allergenicity were predicted for the PE_PGRS17 biomarker, specific B- and T-cell epitope sequences, and the final multiple epitope vaccine (MEV) construct. Algorithmic tools predicted the T- and B-cell epitopes and those that met the immunogenic properties were selected to construct the MEV candidate for predicted vaccine development. The epitopes were joined via linkers and an adjuvant was attached to the terminals of the entire vaccine construct. Immunogenic properties, and physicochemical and structural predictions gave insight into the MEV construct. The assembled vaccine candidate was docked with a receptor and validated using web-based tools. An immune simulation was performed to imitate the immune response after exposure to a dosed administrated predicted MEV subunit. An in silico cloning and codon optimisation gave insight into optimal expression conditions regarding the MEV candidate. In conclusion, the generated MEV construct may potentially emit both cellular and humoral responses which are vital in the development of a peptide-based vaccine against Mtb; nonetheless, further experimental validation is still required.

     

Multiple Sclerosis: Fas Signaling in Oligodendrocyte Cell Death

Fas is a cell surface receptor that transduces cell death signals when cross-linked by agonist antibodies or by fas ligand. In this study, we examined the potential of fas to contribute to oligodendrocyte (OL) injury and demyelination as they occur in the human demyelinating disease multiple sclerosis (MS). Immunohistochemical study of central nervous system (CNS) tissue from MS subjects demonstrated elevated fas expression on OLs in chronic active and chronic silent MS lesions compared with OLs in control tissue from subjects with or without other neurologic diseases. In such lesions, microglia and infiltrating lymphocytes displayed intense immunoreactivity to fas ligand. In dissociated glial cell cultures prepared from human adult CNS tissue, fas expression was restricted to OLs. Fas ligation with the anti-fas monoclonal antibody M3 or with the fas–ligand induced rapid OL cell membrane lysis, assessed by LDH release and trypan blue uptake and subsequent cell death. In contrast to the activity of fas in other cellular systems, dying OLs did not exhibit evidence of apoptosis, assessed morphologically and by terminal transferase–mediated d-uridine triphosphate-biotin nick-end-labeling staining for DNA fragmentation. Other stimuli such as C2-ceramide were capable of inducing rapid apoptosis in OLs. Antibodies directed at other surface molecules expressed on OLs or the M33 nonactivating anti-fas monoclonal antibody did not induce cytolysis of OLs. Our results suggest that fas-mediated signaling might contribute in a novel cytolytic manner to immune-mediated OL injury in MS.     

Behavioral characterization of the novel GABAB receptor-positive modulator GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolytic-like activity without side effects associated with baclofen or benzodiazepines

The role of GABAB receptors in various behavioral processes has been largely defined using the prototypical GABAB receptor agonist baclofen. However, baclofen induces sedation, hypothermia and muscle relaxation, which may interfere with its use in behavioral paradigms. Although there is much evidence for a role of the inhibitory neurotransmitter GABA in the pathophysiology of anxiety, the role of GABAB receptors in these disorders is largely unclear. We recently identified GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine) as a selective allosteric positive modulator at GABAB receptors. The aim of the present study was to broadly characterize the effects of GS39783 in well-validated rodent models for motor activity, cognition, and anxiety. The following tests were included: locomotor activity in rats and mice, rotarod and traction tests (including determinations of core temperature) in mice, passive avoidance in mice and rats, elevated plus maze in rats, elevated zero maze in mice and rats, stress-induced hyperthermia in mice, and pentobarbital- and ethanol-induced sleep in mice. Unlike baclofen and/or the benzodiazepine chlordiazepoxide, GS39783 had no effect in any of the tests for locomotion, cognition, temperature, or narcosis. Most interestingly, GS39783 had anxiolytic-like effects in all the tests used. Overall, the data obtained here suggest that positive modulation of GABAB receptors may serve as a novel therapeutic strategy for the development of anxiolytics, with a superior side effect profile to both baclofen and benzodiazepines.     

The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system.