Binge drinking in male adolescent rats and its relationship to persistent behavioral impairments and elevated proinflammatory/proapoptotic proteins in the cerebellum.

RATIONALE: To demonstrate that repeated episodes of binge drinking during the adolescent period can lead to long-term deficits in motor function and memory in adulthood, and increase proteins in the brain involved with inflammation and apoptotic cell death. METHODS: Groups of early adolescent (PND 26) and periadolescent (PND 34) Sprague-Dawley rats were exposed to either ethanol or plain air through a vapor chamber apparatus for five consecutive days (2 h per day), achieving a blood ethanol concentration equivalent to 6-8 drinks in the treatment group. Subjects then underwent a series of behavioral tests designed to assess memory, anxiety regulation, and motor function. Brains were collected on PND 94 for subsequent western blot analysis. RESULTS: Behavioral testing using the rota-rod, cage-hang, novel object recognition, light-dark box, and elevated plus maze apparatuses showed significant differences between groups; several of which persisted for up to 60 days after treatment. Western blot testing indicated elevated levels of caspase-3/cleaved caspase-3, NF-kB, and PKC/pPKC proteins in the cerebella of ethanol-treated animals. CONCLUSIONS: Differences on anxiety tests indicate a possible failure of behavioral inhibition in the treatment group leading to riskier behavior. Binge drinking also impairs motor coordination and object memory, which involve the cerebellar and hippocampal brain regions, respectively. These experiments indicate the potential dangers of binge drinking while the brain is still developing and indicate the need for future studies in this area.

Pyoderma Gangrenosum-like Wounds in Leukocyte Adhesion Deficiency: Case Report and Review of Literature.

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency characterized by impairment of leukocyte migration during an inflammatory response. LAD patients can experience recurrent neutrophilic wounds similar to pyoderma gangrenosum (PG), predominantly of the skin and mucosal surfaces. There have been only a few reports addressing the management of extensive, life-threatening wounds in LAD patients. We describe here both the systemic and local management employed to successfully treat a severe PG-like cutaneous lesion in the setting of LAD in a 9-year-old female. A comprehensive literature review was performed to identify previously reported similar cases. Under aggressive systemic and local management, the wound was stabilized and complete epithelialization was achieved in 8 months. Eight studies documenting 11 patients with LAD and PG-like lesions were identified in our review of the literature. The complexity of wounds associated with LAD requires an aggressive, multidisciplinary approach. Involvement of pediatrics, immunology, plastic surgery, infectious disease, and physical therapy is essential to obtaining a positive outcome. In the setting of LAD with PG-like lesions, the only viable option is allowing for closure by secondary epithelialization. This was achieved in our patient once the wound was stabilized with the systemic administration of infliximab and topical administration of tacrolimus.

Understanding persuasive attributes of sports betting advertisements: A conjoint analysis of selected elements.

Background and aims Despite recent growth in sports betting advertising, minimal research has examined the influence of different advertising message attributes on betting attitudes and behaviors. This study aimed to identify which attributes of sports betting advertisements most engage attention, interest, desire and likelihood of betting among non-problem, low-risk, moderate-risk, and problem gamblers. Methods A novel approach utilizing an experimental design incorporating conjoint analysis examined the effects of: three message formats (commentary, on-screen display, and studio crossover); four appeals (neutral, jovial, ease of placing the bet, and sense of urgency); three types of presenters (match presenter, sports betting operator, and attractive non-expert female presenter); and four bet types (traditional, exotic key event, risk-free, and micro-bet). A professional film company using paid actors produced 20 mock television advertisements simulating typical gambling messages based on the conjoint approach. These were embedded into an online survey of 611 Australian adults. Results The most attention-grabbing attributes were type of presenter and type of bet. The attractive non-expert female presenter gained more attention from all gambler groups than other presenters. The type of bet was most persuasive in converting attention into likely betting among all gambler groups, with the risk-free bet being much more persuasive than other bet types. Problem gamblers were distinct by their greater attraction to in-play micro-bets. Discussion and conclusion Given the potential for incentivized bets offering financial inducements and for in-play micro-bets to undermine harm minimization and consumer protection, regulators and wagering operators should reconsider whether these bet types are consistent with their responsible gambling objectives.

Bet Anywhere, Anytime: An Analysis of Internet Sports Bettors' Responses to Gambling Promotions During Sports Broadcasts by Problem Gambling Severity.

Promotions for online sports betting during televised sports broadcasts are regularly viewed by millions of Australians, raising concerns about their impacts on vulnerable groups including at-risk and problem gamblers. This study examined whether responses to these promotions varied with problem gambling severity amongst 455 Australian Internet sports bettors participating in an online survey. Results indicated that young male Internet sports bettors are especially vulnerable to gambling problems, particularly if they hold positive attitudes to gambling sponsors who embed promotions into sports broadcasts and to the promotional techniques they use and this heightens the risk that alluring messages contribute to excessive gambling. As problem gambling severity increased, so too did recognition that these promotions have impacted negatively on their sports betting behaviour. Because a plethora of sports betting brands and promotions are now heavily integrated into sports coverage, social marketing efforts are needed to offset their persuasive appeal and counter the positive attitudes towards them that appear linked to excessive gambling amongst Internet sports bettors.

Demographic, Behavioural and Normative Risk Factors for Gambling Problems Amongst Sports Bettors.

Sports betting is growing exponentially, is heavily marketed and successfully targets young adult males. Associated gambling problems are increasing. Therefore, understanding risk factors for problem gambling amongst sports bettors is an increasingly important area of research to inform the appropriate design and targeting of public health and treatment interventions. This study aimed to identify demographic, behavioural and normative risk factors for gambling problems amongst sports bettors. An online survey of 639 Australian sports bettors using online, telephone and retail betting channels was conducted. Results indicated that vulnerable sports bettors for higher risk gambling are those who are young, male, single, educated, and employed full-time or a full-time student. Risk of problem gambling was also found to increase with greater frequency and expenditure on sports betting, greater diversity of gambling involvement, and with more impulsive responses to betting opportunities, including in-play live action betting. Normative influences from media advertising and from significant others were also associated with greater problem gambling risk. The results of this study can inform a suite of intervention, protection and treatment initiatives targeted especially at young male adults and adolescents that can help to limit the harm from this gambling form.

Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication.

Potential neuroprotective effects of oxyresveratrol against traumatic injury.

Oxyresveratrol is a potent antioxidant and free-radical scavenger found in mulberry wood (Morus alba L.) with demonstrated protective effects against cerebral ischemia. We analyzed the neuroprotective ability of oxyresveratrol using an in vitro model of stretch-induced trauma in co-cultures of neurons and glia, or by exposing cultures to high levels of glutamate. Cultures were treated with 25 µM, 50 µM or 100 µM oxyresveratrol at the time of injury. Trauma produced marked neuronal death when measured 24 h post-injury, and oxyresveratrol significantly inhibited this death. Microscopic examination of glia suggested signs of toxicity in cultures treated with 100 µM oxyresveratrol, as demonstrated by elevated S-100B protein release and a high proportion of cells with condensed nuclei. Cultures exposed to glutamate (100 µM) for 24 h exhibited ~ 37% neuronal loss, which was not inhibited by oxyresveratrol. These results show that the two pathologies of high glutamate exposure and trauma are differentially affected by oxyresveratrol treatment in vitro. Further studies using oxyresveratrol in trauma models are warranted, as toxicity to glia could be beneficial by inhibiting reactive gliosis, which often occurs after trauma.

The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex.

The cerebellum is important for motor coordination, as well as motor learning and memories. Learning is believed to occur in the cerebellar cortex, in the form of synaptic plasticity. Central to motor learning theory are Purkinje cells (PCs), which are the sole output neurons of the cerebellar cortex. Motor memories are postulated to be stored in the form of long-term depression (LTD) at parallel fiber synapses with PCs, once thought to be the only plastic synapse in the cerebellar cortex. However, in the past few decades many studies have demonstrated that several other synapses in the cerebellar cortex are indeed plastic, and that LTD or long-term potentiation at these various synapses could affect the overall output signal of PCs from the cerebellar cortex. Almost all of these forms of synaptic plasticity are dependent on calcium to some extent. In the current review we discuss various types of synaptic plasticity in the cerebellar cortex and the role of calcium in these forms of plasticity.