Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model

Recent studies using a mouse model of weight-drop-induced "diffuse" traumatic brain injury (TBI) have demonstrated a substantial gender difference in the time course and magnitude of post-traumatic neurodegeneration following a severe level of injury. The time of maximal damage, as assessed by the de Olmos aminocupric silver staining method, occurred at 72 h in male mice, whereas the peak of neurodegeneration was not observed until 14 days in females and was less in magnitude compared to males. This difference, favoring females, has been postulated to relate to the neuroprotective actions of estrogen and progesterone. In the presently reported experiments, we compared the time course and peak of neurodegeneration in male and female mice after a severe level of "focal" controlled cortical impact (CCI; 1 mm, 3.5 m/sec) TBI using the same strain (CF-1) and weight (29-31 g) as employed in the "diffuse" TBI study. The volume of silver staining was measured using image analysis methods at 24, 48, and 72 h, and 1, 2 and 4 weeks. In male and female mice, a significant increase in neurodegeneration was observed at 24 h, and the volume was not significantly different between the two genders. In both gender groups, the maximal neurodegeneration was seen at 48 h after injury. Although the female mice exhibited a trend toward higher mean volumes of silver staining, this difference was not significantly different compared to males. Furthermore, the rate of resolution of staining between 48 h and 4 weeks was similar. However, injured females still exhibited a significantly higher volume of staining compared to sham, non-injured females at 4 weeks, whereas the difference in staining volume between sham and injured males was no longer significant at that time point. These results show that, following a "focal" CCI, there is no gender difference that favors females, in contrast to that seen with the "diffuse" injury paradigm. The disparity between the effects of gender in the two models may be due to the fact that, in the "focal" CCI model, the timing of post-traumatic neurodegeneration is significantly more rapid than that seen in the "diffuse" model, which may overwhelm the neuroprotective effects of estrogen and progesterone and obscure the appearance of a gender difference.     

Headache symptoms in pediatric sickle cell patients

The purposes of this study were to determine the characteristics of headaches in children with sickle cell disease (SCD) and to assess the relationship between headache symptoms and children's physical and emotional status. A detailed headache questionnaire using International Classification of Headache Disorders (ICHD-2) criteria was mailed to a cohort (n = 50) of children with SCD, ages 9 to 17 years. Respondents also completed measures of functional disability and psychological distress. Headaches had occurred over the previous 3-month period in 76.2% of the patients. Frequent headaches were common, occurring greater than once a week in 31.2% of children. Average pain severity was reported as moderate on a 0-to-10 scale (mean = 5.8). Duration of headaches ranged from 30 minutes to several days, with a mean of 5 hours. Based on ICHD-2 criteria, 43.8% of children had headache symptoms consistent with migraines, 6.2% with migraine with aura, and 50.0% with tension-type headaches. Children with symptoms of migraine had significantly greater functional disability compared with children with symptoms of tension-type headaches (P < 0.01). Further studies to determine the characteristics and determinants of headaches experienced in SCD patients will help maximize treatment of headaches and enhance daily functioning in these patients.     

Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.     

Cross-national consistency in the relationship between bullying behaviors and psychosocial adjustment

OBJECTIVE: To determine whether the relationship between bullying and psychosocial adjustment is consistent across countries by standard measures and methods. DESIGN: Cross-sectional self-report surveys were obtained from nationally representative samples of students in 25 countries. Involvement in bullying, as bully, victim, or both bully and victim, was assessed. SETTING: Surveys were conducted at public and private schools throughout the participating countries. PARTICIPANTS: Participants included all consenting students in sampled classrooms, for a total of 113 200 students at average ages of 11.5, 13.5, and 15.5 years. MAIN OUTCOME MEASURES: Psychosocial adjustment dimensions assessed included health problems, emotional adjustment, school adjustment, relationships with classmates, alcohol use, and weapon carrying. RESULTS: Involvement in bullying varied dramatically across countries, ranging from 9% to 54% of youth. However, across all countries, involvement in bullying was associated with poorer psychosocial adjustment (P<.05). In all or nearly all countries, bullies, victims, and bully-victims reported greater health problems and poorer emotional and social adjustment. Victims and bully-victims consistently reported poorer relationships with classmates, whereas bullies and bully-victims reported greater alcohol use and weapon carrying. CONCLUSIONS: The association of bullying with poorer psychosocial adjustment is remarkably similar across countries. Bullying is a critical issue for the health of youth internationally.     

Assessment of risk factors for emergence distress and postoperative behavioural changes in children following general anaesthesia

BACKGROUND: Emergence distress commonly occurs in children recovering from the immediate effects of general anaesthesia. This study was performed to (1) examine whether parental presence in the operating room during emergence from anaesthesia reduces the incidence or severity of emergence distress behaviour, and (2) assess psychosocial risk factors, including child temperament and sleep behaviour, for development of emergence distress. METHODS: A randomized and controlled trial of parental presence at emergence was conducted in 100 ASA class I and II children having general anaesthesia for inguinal or penile surgery. Children in the study group had a parent present at induction and emergence of anaesthesia, while children in the control group had a parent present only at induction. Emergence and postanaesthesia care unit (PACU) behaviour was monitored using both the Operating Room Behaviour Rating Scale (ORBRS) and a 7-point Likert type cooperation scale. RESULTS: One-way anovas showed no significant differences between the control group and the study group on emergence distress behaviour. The frequency of negative postoperative behavioural changes at 1 and 4 weeks postsurgery was low in both groups. Children described as clingy/dependent (chi2 = 5.57, P < 0.06) and children with frequent temper tantrums (chi2 = 7.44, P < 0.02) were more likely to have emergence distress behaviour. CONCLUSIONS: Parental presence during emergence from anesthesia did not decrease the incidence or severity of emergence distress behaviour in children. Young children and children with a history of temper tantrums or separation anxiety may be more likely to develop such behaviour.     

Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase

Long chain acyl-CoA dehydrogenase (LCAD) has recently been shown to be the mitochondrial enzyme responsible for the beta-oxidation of branched chain and unsaturated fatty acids [Biochim. Biophys. Acta 1393 (1998) 35; Biochim. Biophys. Acta 1485 (2000) 121]. Whilst disorders of short, medium and very long chain acyl dehydrogenases are known, there is no known disorder of LCAD deficiency in humans. Experimental LCAD deficiency in mice shows an acyl-carnitine profile with prominent elevations of unsaturated fatty acid metabolites C14:1 and C14:2 [Hum. Mol. Genet. 10 (2001) 2069]. A child with autism whose acyl-carnitine profile also shows these abnormalities is presented, and it is hypothesized that the child may have LCAD deficiency. Additional metabolic abnormalities seen in this patient include alterations of TCA energy production, ammonia detoxification, reduced synthesis of omega-3 DHA, and abnormal cholesterol metabolism. These metabolic changes are also seen as secondary abnormalities in dysfunction of fatty acid beta-oxidation, and have also been reported in autism. It is hypothesized that LCAD deficiency may be a cause of autism. Similarities between metabolic disturbances in autism, and those of disorders of fatty acid beta-oxidation are discussed.     

Concurrent sexual partnerships among African Americans in the rural south

PURPOSE: To investigate concurrent sexual partnerships among heterosexual African Americans, 18 to 59 years old, in rural North Carolina. METHODS: Household interviews with persons randomly selected from the NC driver's license file were conducted to identify overlap among the 3 most recent sexual partnerships. RESULTS: Concurrency prevalence in the past 5 years was 53% (men) and 31% (women). Most (61%) respondents believed that a recent partner had had a concurrent partnership. Multivariate analysis revealed strong associations between concurrency and male gender, being unmarried, age of sexual debut, and incarceration of a sex partner. CONCLUSIONS: Concurrent partnerships may increase rates of heterosexual HIV among blacks in the rural Southeastern United States. Future research should examine the context that supports this network pattern.     

Coagulation in sepsis

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.     

Actin-binding proteins in a postsynaptic preparation: Lasp-1 is a component of central nervous system synapses and dendritic spines

CNS synapses are complex sites of cell-cell communication. Identification and characterization of the protein components of synapses will lead to a better understanding of the mechanisms of neurotransmission and plasticity. We applied multidimensional protein identification technology (MudPIT) to purified, guanidine-solubilized postsynaptic fractions to identify novel synaptically localized molecules. We identified several actin-associated proteins known to regulate actin polymerization and control cell motility in nonneural cells that have not previously been associated with CNS synaptic function. One of these is lasp-1, an actin-associated LIM and SH3 domain-containing protein. We show that lasp-1 is strongly expressed by CNS neurons and is concentrated at synaptic sites. Overall, the preponderance of actin-associated proteins in postsynaptic density fractions, and specifically those involved in actin reorganization, suggests that there are many modes by which the state of synaptic F-actin polymerization and, hence, synaptic physiology are affected.