Minor physical anomalies and family adversity as risk factors for violent delinquency in adolescence

OBJECTIVE: Minor physical anomalies are considered indicators of disruption in fetal development. They have been found to predict behavioral problems and psychiatric disorders. This study examined the extent to which minor physical anomalies, family adversity, and their interaction predict violent and nonviolent delinquency in adolescence. METHOD: Minor physical anomalies were assessed in a group of 170 adolescent boys from low socioeconomic status neighborhoods of Montréal. The boys had been enrolled in a longitudinal study since their kindergarten year, when an assessment of family adversity had been made on the basis of familial status and the parents' occupational prestige, age at the birth of the first child, and educational level. Adolescent delinquency was measured by using self-reported questionnaires and a search of official crime records. RESULTS: Results from logistic regression analyses indicated that both the total count of minor physical anomalies and the total count of minor physical anomalies of the mouth were significantly associated with an increased risk of violent delinquency in adolescence, beyond the effects of childhood physical aggression and family adversity. Similar findings were not found for nonviolent delinquency. CONCLUSIONS: Children with a higher count of minor physical anomalies, and especially a higher count of anomalies of the mouth, could be more difficult to socialize for different and additive reasons: they may have neurological deficits, and they may have feeding problems in the first months after birth. Longitudinal studies of infants with minor physical anomalies of the mouth are needed to understand the process by which they fail to learn to inhibit physical aggression.     

Behavioural Development in Children of Divorce and Remarriage

We employed an autoregressive modelling technique with data from the Quebec Longitudinal Study to prospectively examine the developmental impact of family transition on behaviour while controlling for predivorce and preremarriage effects. Teachers rated children's anxious, hyperactive, physically aggressive, oppositional, and prosocial behaviour every 2 years from kindergarten through to the end of elementary school.Once individual and parental characteristics and antecedent family events were controlled, children who experienced parental divorce before age 6 exhibited comparatively more behavioural disturbance than their peers whose parents divorced later. With the exception of a protective effect on hyperactive behaviour, remarriage did not have a significant impact on children's behaviour when the legacy of divorce was controlled.Although the results suggest that children of divorced parents show difficulty in many areas of functioning, the effects of family transition on behavioural development were dependent on the child's age and the specific behavioural dimension assessed.Compared to other points in development, early childhood divorce was associated with long-term increases in anxious, hyperactive, and oppositional behaviour during later childhood.The effects of divorce on children's fighting were short-lived.Unlike previous prospective studies that suggest predivorce effects, we did not observe behavioural disturbance prior to divorce or remarriage.     

Problem-based learning in occupational therapy: why do health professionals choose to tutor?

For over 20 years the occupational therapy programmes offered by McMaster University and Mohawk College, Hamilton, Ontario have used small-group, problem-based learning tutorials as a major component of their curriculum. These programmes were among the first occupational therapy programmes in the world to use a problem-based tutorial format. The inclusion as tutors of both full-time faculty and clinicians, from all clinical practice areas, was central to the design of the problem-based learning courses. A survey of all tutors from the last 20 years collected information about why health professionals are motivated to tutor and what they see as challenges to maintaining this educational role. Three primary themes emerged from the data: being an educator; being a learner and present and future challenges to continuing with the tutoring role. Within the educator theme there was a secondary theme of professional duty or obligation. In addition, the participants identified suggestions for enhanced support and continuing education for tutors. This article summarizes the findings of the survey.     

Feasibility of a randomized controlled trial testing nifedipine vs. placebo for the treatment of preterm labor

AIMS: Nifedipine is believed to be a superior tocolytic agent on the basis of efficacy and side-effect profile, but was never prospectively evaluated in a placebo-controlled randomized clinical trial (RCT). In our study, we sought to identify limitations in participation for a would-be RCT comparing nifedipine to placebo. METHODS: A prospective feasibility study was conducted at Ste-Justine Hospital, a tertiary care center, on women between 24 and 34 weeks' gestation, presenting to the labor and delivery room with obstetrical complaints. Patient information was collected and would-be participants were identified on the basis of pre-established clinical and ultrasound criteria as well as on willingness to participate, as determined by the study research nurse. RESULTS: During a 6-month period, 483 women presenting with signs and symptoms of preterm labor (PTL) were eligible for further evaluation. A total of 321 (66.5%) women were excluded for obstetrical and medical reasons whereas 125 (25.9%) did not meet strict inclusion criteria (cervical length <25 mm or positive fetal fibronectin). When using strict criteria, only 37 women (7.6%) were found to be eligible for study participation. Subject willingness to participate as assessed by the research nurse was 50%. CONCLUSIONS: If adhering to strict inclusion/exclusion criteria, the feasibility of an appropriately sampled RCT testing tocolytic therapy against a placebo would require a large concerted multicenter effort to meet sample size demands.     

Heparin-induced thrombocytopenia syndrome as a cause of flap failure: a report of two cases.

BACKGROUND: Flap failure is a major complication in reconstructive plastic surgery. One of the most frequent etiologies of flap failure is venous thrombosis. However, infrequent causes also need to be explored, especially when faced with recurrent thrombosis. Heparin is frequently used in the prevention of venous thrombosis; however, the use of the medication itself may cause a serious thromboembolic state via an immune-related pathophysiological process. This adverse reaction to heparin may be life threatening. CASE PRESENTATION: We present two cases, one pedicled and one free flap, with venous congestion concomitant to heparin-induced thrombocytopenia syndrome, in conjunction with severe life-threatening sequelae. CONCLUSIONS: Heparin-induced thrombocytopenia syndrome can be the cause of postoperative venous congestion. It is necessary to be alert for this syndrome in the presence of recurrent unexplained venous thrombosis or thrombocytopenia in patients receiving anticoagulation therapy.     

Combined immunosuppression of mycophenolate mofetil and FK506 for myoblast transplantation in mdx mice

BACKGROUND: Overcoming adverse effects of immunosuppressors can be achieved by combining different drugs, thus allowing a dosage reduction. Myoblast transplantation is a potential therapy for Duchenne muscular dystrophy. Our research group previously established that FK506 (tacrolimus) is an effective immunosuppressive drug for myoblast transplantation in mice and monkeys. METHODS: In the present study, a reduced dose of FK506 at 1.0 mg/kg/day was used in combination with mycophenolate mofetil (MMF; 80 mg/kg/day) as an immunosuppressive protocol for myoblast transplantation. Graft success was evaluated by quantifying the number of dystrophin-positive fibers per muscle section that were injected with normal cells. RESULTS: MMF used alone could not prevent immune rejection of the transplanted myoblasts. MMF given in combination with FK506 immediately after transplantation reduced the success of myoblast transplantation by about 50%. A low dose of FK506 combined with MMF after the establishment of the graft (3 weeks) maintained graft success and controlled immune infiltration compared with a low dose of FK506 alone. However, lymphocyte infiltration was observed at longer term using a low dose of FK506 combined with MMF. CONCLUSIONS: The diminution of graft success when combining FK506 and MMF by the time of myoblast transplantation could be attributed to the inhibition of myoblast fusion by MMF. The use of MMF and FK506 after the establishment of the graft did not reduce graft success, however, this combination was not effective at controlling long-term immune rejection in comparison with the optimal dose of FK506 alone.     

Waist Circumference is Useless to Assess the Prevalence of Metabolic Abnormalities in Severely Obese Women

BACKGROUND: The present retrospective study aims to provide additional evidence supporting the fact that waist circumference, in severe obesity, is not a good clinical marker to identify individuals with the metabolic syndrome or an altered metabolic profile. METHODS: Relationships between waist circumference and metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women were compared to associations observed in pre- (n=52) and postmenopausal (n=35) moderately obese women. RESULTS: Results showed that abdominal obesity assessed by waist circumference was more highly correlated with fasting glycemia, HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in severely obese women, before menopause. After menopause, waist circumference was not a valuable predictor of metabolic abnormalities in both groups. Moreover, when waist circumference was included as a criterion of the metabolic syndrome (as defined by the NCEP ATP III guidelines) in severely obese women, the prevalence of this metabolic condition was over-estimated by 72%. CONCLUSION: These results emphasize the uselessness of waist circumference to assess the prevalence of the metabolic syndrome or an altered metabolic profile in severely obese women.     

Novel Duchenne Muscular Dystrophy Treatment Through Myoblast Transplantation Tolerance with Anti-CD45RB, Anti-CD154 and Mixed Chimerism

Duchenne muscular dystrophy (DMD) is a fatal disease caused by a defect in the skeletal muscle protein, dystrophin. One potential therapy for DMD involves transplantation of myoblasts from normal individuals. Unfortunately, myoblast allografts are particularly immunogenic and transplant tolerance in dystrophic (mdx/mdx) mice has not yet been achieved despite using strategies successful in other allograft models. Here, we attempted to induce 'central tolerance' using either haplo- or fully allogeneic bone marrow after conditioning with low-dose (3 Gy) whole body irradiation and anti-CD154 or anti-CD45RB mAbs. With one exception, these mice lacked persistent chimerism, long-term survival of myoblast allografts, or tolerance. In contrast, the addition of anti-CD45RB to anti-CD154 uniformly resulted in long-lived high-level mixed chimerism, long-term (>100 days) engraftment of allogeneic myoblasts and deletion of donor-reactive cells. Moreover, all recipients exhibited tolerance to second myoblast allografts or donor-specific tolerance to skin transplants performed >80 days after the initial graft. Thus, we now report that anti-CD45RB synergizes with anti-CD40L to promote stable mixed chimerism and robust tolerance to myoblast allografts for the first time. This novel protocol may be applicable to future clinical trials in myoblast transplantation for treatment of DMD and for transplantation of other immunogenic allografts.     

Myoblast survival enhancement and transplantation success improvement by heat-shock treatment in mdx mice

BACKGROUND: Duchenne muscular dystrophy is a disease caused by the incapacity to synthesize dystrophin, which is implicated in the maintenance of the sarcolemma integrity. Myoblast transplantation is a potential treatment of this disease. However, most of the transplanted cells die very rapidly after their injection. Heat-shock proteins (HSPs) are over-expressed when cells undergo various types of stresses. Our goal was thus to investigate whether the expression of HSPs (HSP70 in particular) could protect myoblasts from death after intramuscular injection. METHODS: HSP70 expression was induced by warming the cells at 42 degrees C for 60 minutes. HSP70 over-expression was quantified by Western blot analysis. The in vitro effect of HSPs on cell survival was evaluated by fluorescence-activated cell sorter analysis using the Hoescht/propidium iodide-labeling technique, and their in vivo effects were investigated by transplanting TnI-LacZ myoblasts labeled with [methyl-14C] thymidine. RESULTS: Western blots indicated a sevenfold over-expression of the HSP70 after the heat-shock treatment. In vitro, the heat-shock treatment protected 18% of the cells from staurosporine- (1 microM) induced apoptosis. HSPs also protected 10% of the cells from death induced by either tumor necrosis factor-alpha (30 ng/mL) or glucose oxydase (0.1 U/mL). In vivo, the treatment improved the cell survival by twofold 5 days after the graft and increased by fourfold the long-term graft success. CONCLUSIONS: The heat-shock treatment is a practical approach for improving the success of myoblast transplantation; in fact, using this kind of treatment, there is no need to genetically modify the cells before their transplantation.     

Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes

Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.