Coping and family functions after closed head injury

Cognitive deficits associated with closed head injury (CHI) have been well studied. Less attention has been directed to the emotional consequences of CHI and subsequent attempts to cope with major life events. CHI typically constitutes a catastrophic injury, yet few studies have examined coping strategies used by individuals after CHI or the effects of CHI on family functioning that may mediate coping. Previous workers have speculated that time since injury is a crucial determinant of coping; however, this has not been investigated with regard to CHI. In this preliminary investigation, 40 patients with CHI were compared with 17 neurologically intact controls. The CHI group was divided into two groups according to time since injury. It was found that patients with CHI used information seeking as their most dominant coping strategy regardless of their time since injury. Patients with CHI had higher family cohesion scores than control subjects. Implications of these findings for psychological response to CHI are discussed.     

Levetiracetam Inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture

Epilepsy affects approximately 1% of the population worldwide, and there is a pressing need to develop new anti-epileptic drugs (AEDs) and understand their mechanisms of action. Levetiracetam (LEV) is a novel AED and despite its increasingly widespread clinical use, its mechanism of action is as yet undetermined. Intracellular calcium ([Ca²⁺]_i) regulation by both inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR) has been implicated in epileptogenesis and the maintenance of epilepsy. To this end, we investigated the effect of LEV on RyR and IP3R activated calcium-induced calcium release (CICR) in hippocampal neuronal cultures. RyR-mediated CICR was stimulated using the well-characterized RyR activator, caffeine. Caffeine (10 mM) caused a significant increase in [Ca²⁺]_i in hippocampal neurons. Treatment with LEV (33 μM) prior to stimulation of RyR-mediated CICR by caffeine led to a 61% decrease in the caffeine induced peak height of [Ca²⁺]_i when compared to the control. Bradykinin stimulates IP3R-activated CICR—to test the effect of LEV on IP3R-mediated CICR, bradykinin (1 μM) was used to stimulate cells pre-treated with LEV (100 μM). The data showed that LEV caused a 74% decrease in IP3R-mediated CICR compared to the control. In previous studies we have shown that altered Ca²⁺ homeostatic mechanisms play a role in seizure activity and the development of spontaneous recurrent epileptiform discharges (SREDs). Elevations in [Ca²⁺]_i mediated by CICR systems have been associated with neurotoxicity, changes in neuronal plasticity, and the development of AE. Thus, the ability of LEV to modulate the two major CICR systems demonstrates an important molecular effect of this agent on a major second messenger system in neurons.     

Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH(3). TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance.     

“I’ve Had an Alarm Set for 3:00 a.m. for Decades”: The Impact of Type 1 Diabetes on Sleep

There is a dearth of research characterizing the impact on a caregiver’s sleep when caring for a minor with type 1 diabetes. This study used focus groups of people with type 1 diabetes and caregivers of minors with type 1 diabetes to explore the experience of how diabetes affects sleep. The occurrence of both unanticipated and planned sleep disruptions led to the majority of participants reporting that their sleep was considerably affected by diabetes. Despite the improvement in blood glucose management that diabetes technology devices can provide, people with type 1 diabetes and their caregivers still report sleep disruption and sleep loss resulting from overnight diabetes management.

The daily self-management behaviors involved in living with type 1 diabetes can be more difficult overnight for people with type 1 diabetes, caregivers, and other household members and can lead to sleep disruptions and emotional experiences such as worrying about severe hypoglycemia occurring during sleep. On average, people with type 1 diabetes experience nocturnal hypoglycemia 25% of the time (1). Emotional experiences can also include fear of hypoglycemia, which refers to extreme worry and anxiety-like symptoms experienced by people living with type 1 diabetes and their caregivers regarding hypoglycemia. Such feelings can result in negative diabetes management behaviors and negatively affect quality of life (2,3). Disturbances caused by diabetes device alarms and fear of hypoglycemia are common barriers to sleep for people with diabetes (4). Research suggests that interventions should be developed to target overnight glycemic management and fear of hypoglycemia to improve sleep quality (5).     

Quantitative differences in lipid raft components between murine CD4<Superscript>+</Superscript> and CD8<Superscript>+</Superscript> T cells

Background  

Lipid rafts have been shown to play a role in T cell maturation, activation as well as in the formation of immunological synapses in CD4⁺ helper and CD8⁺ cytotoxic T cells. However, the differential expression of lipid raft components between CD4⁺ and CD8⁺ T cells is still poorly defined. To examine this question, we analyzed the expression of GM1 in T cells from young and aged mice as well as the expression of the glycosylphosphatidylinositol (GPI)-linked protein Thy-1 and cholesterol in murine CD4⁺ and CD8⁺ T cell subpopulations.     

Epilepsy and seizure occurrence in a population-based sample of Virginian twins and their families

Epilepsy and seizure occurrence was assessed in a large, population-based sample of Virginian twins and their families. Medical history information on twins and their relatives was collected by questionnaire and used to estimate prevalence of seizures and epilepsy for this sample. Health history information was available on 16,634 twins and their families. Lifetime prevalence of a history of seizures ranged from < 1 to 5%. Concordance rates were larger in monozygotic (MZ) than dizygotic (DZ) pairs overall, however, significant differences between the zygosities were only noted for Caucasian twins. To facilitate interpretation of results, the sample was partitioned into two age groups: 16-35 years and > 35 years of age. In the first age category of twins, significant differences were observed for the following seizure types; epilepsy (0.30 and 0.13, p <0.03), febrile seizures (0.39 and 0.12, p <0.001), and other convulsions/seizures (0.28 and 0.01, p < 0.001). While for twins in the second age category, only the comparison for febrile seizures (0.42 and 0.14, p < 0.001) resulted in a significant difference between zygosities. A family history of seizures was reported in 215 (35.1%) of the 613 seizure positive probands. Increased risk of seizures (1.88-4.64) among relatives of affected versus unaffected individuals was also observed.     

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.     

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.