1,909 research outputs found

    Increased Action Potential Firing Rates of Layer 2/3 Pyramidal Cells in the Prefrontal Cortex are Significantly Related to Cognitive Performance in Aged Monkeys

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    The neurobiological substrates of significant age-related deficits in higher cognitive abilities mediated by the prefrontal cortex (PFC) are unknown. To address this issue, whole-cell current-clamp recordings were used to compare the intrinsic membrane and action potential (AP) firing properties of layer 2/3 pyramidal cells in PFC slices from young and aged behaviorally characterized rhesus monkeys. Most aged subjects demonstrated impaired performance in Delayed Non-Match to Sample (DNMS) task acquisition, DNMS 2 min delay and the Delayed Recognition Span task. Resting membrane potential and membrane time constant did not differ in aged relative to young cells, but input resistance was significantly greater in aged cells. Single APs did not differ in terms of threshold, duration or rise time, but their amplitude and fall time were significantly decreased in aged cells. Repetitive AP firing rates were significantly increased in aged cells. Within the aged group, there was a U-shaped quadratic relationship between firing rate and performance on each behavioral task. Subjects who displayed either low or very high firing rates exhibited poor performance, while those who displayed intermediate firing rates exhibited relatively good performance. These data indicate that an increase in AP firing rate may be responsible, in part, for age-related PFC dysfunction

    Guanabenz repurposed as an antiparasitic with activity against acute and latent toxoplasmosis

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    Toxoplasma gondii is a protozoan parasite that persists as a chronic infection. Toxoplasma evades immunity by forming tissue cysts, which reactivate to cause life-threatening disease during immune suppression. There is an urgent need to identify drugs capable of targeting these latent tissue cysts, which tend to form in the brain. We previously showed that translational control is critical during infections with both replicative and latent forms of Toxoplasma. Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages of Toxoplasma and the related apicomplexan parasite Plasmodium falciparum (a malaria agent). We also found that inhibition of translational control interfered with tissue cyst biology in vitro. Toxoplasma bradyzoites present in these abnormal cysts were diminished and misconfigured, surrounded by empty space not seen in normal cysts. These findings prompted analysis of the efficacy of guanabenz in vivo by using established mouse models of acute and chronic toxoplasmosis. In addition to protecting mice from lethal doses of Toxoplasma, guanabenz has a remarkable ability to reduce the number of brain cysts in chronically infected mice. Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain

    Hyperspectral Imaging for Burn Depth Assessment in an Animal Model

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    Differentiating between superficial and deep-dermal (DD) burns remains challenging. Superficial-dermal burns heal with conservative treatment; DD burns often require excision and skin grafting. Decision of surgical treatment is often delayed until burn depth is definitively identified. This study\u27s aim is to assess the ability of hyperspectral imaging (HSI) to differentiate burn depth. METHODS: Thermal injury of graded severity was generated on the dorsum of hairless mice with a heated brass rod. Perfusion and oxygenation parameters of injured skin were measured with HSI, a noninvasive method of diffuse reflectance spectroscopy, at 2 minutes, 1, 24, 48 and 72 hours after wounding. Burn depth was measured histologically in 12 mice from each burn group (n = 72) at 72 hours. RESULTS: Three levels of burn depth were verified histologically: intermediate-dermal (ID), DD, and full-thickness. At 24 hours post injury, total hemoglobin (tHb) increased by 67% and 16% in ID and DD burns, respectively. In contrast, tHb decreased to 36% of its original levels in full-thickness burns. Differences in deoxygenated and tHb among all groups were significant (P \u3c 0.001) at 24 hours post injury. CONCLUSIONS: HSI was able to differentiate among 3 discrete levels of burn injury. This is likely because of its correlation with skin perfusion: superficial burn injury causes an inflammatory response and increased perfusion to the burn site, whereas deeper burns destroy the dermal microvasculature and a decrease in perfusion follows. This study supports further investigation of HSI in early burn depth assessment

    Malaria and anaemia among children in two communities of Kumasi, Ghana: a cross-sectional survey

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    BACKGROUND: A survey in Kumasi, Ghana found a marked Plasmodium falciparum prevalence difference between two neighbouring communities (Moshie Zongo and Manhyia). The primary objective of this follow-up study was to determine whether this parasite rate difference was consistent over time. Secondary objectives were to compare prevalences of clinical malaria, anaemia, intestinal parasite infections, and malnutrition between these communities; and to identify potential risk factors for P. falciparum infection and anaemia. METHODS: A cross-sectional house-to-house survey of P. falciparum parasitaemia, clinical malaria, anaemia, anthropometric indices, and intestinal helminths was conducted in April-May 2005. Data collection included child and household demographics, mosquito avoidance practices, distance to nearest health facility, child's travel history, symptoms, and anti-malarial use. Risk factors for P. falciparum and anaemia (Hb < 11 g/dl) were identified using generalized linear mixed models. RESULTS: In total, 296 children were tested from 184 households. Prevalences of P. falciparum, clinical malaria, anaemia, and stunting were significantly higher in Moshie Zongo (37.8%, 16.9%, 66.2% and 21.1%, respectively) compared to Manhyia (12.8%, 3.4%, 34.5% and 7.4%). Of 197 children tested for helminths, four were positive for Dicrocoelium dendriticum. Population attributable risks (PAR%) of anaemia were 16.5% (P. falciparum) and 7.6% (malnutrition). Risk factors for P. falciparum infection were older age, rural travel, and lower socioeconomic status. Risk factors for anaemia were P. falciparum infection, Moshie Zongo residence, male sex, and younger age. CONCLUSION: Heterogeneities in malariometric indices between neighbouring Kumasi communities are consistent over time. The low helminth prevalence, and the twofold higher PAR% of anaemia attributable to P. falciparum infection compared to malnutrition, indicate the importance of malaria as a cause of anaemia in this urban population

    Engaging Low-Income Parents in Childhood Obesity Prevention from Start to Finish: A Case Study

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    Prevention of childhood obesity is a national priority. Parents influence young children’s healthy lifestyles, so it is paradoxical that obesity interventions focus primarily on children. Evidence and theory suggest that including parents in interventions offers promise for effective childhood obesity prevention. This case study engaged parents’ as co-researchers in the design, implementation and evaluation of an intervention for low-income families with a child enrolled in Head Start. Parent engagement mechanisms include: (1) targeted partnership development (2) operationalizing a Community Advisory Board (CAB) that was the key decision making body; (3) a majority of CAB members were parents who were positioned as experts, and (4) addressing structural barriers to parent participation. Lessons learned are provided for future research, and practice
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