Are 1 or 2 dangerous? Clozapine and olanzapine exposure in toddlers

Clozapine (Clozaril) and olanzapine (Zyprexa) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.     

ProDisc–C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study

European Spine Journal - Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment...     

Hemispheric roles in the perception of speech prosody

Speech prosody is processed in neither a single region nor a specific hemisphere, but engages multiple areas comprising a large-scale spatially distributed network in both hemispheres. It remains to be elucidated whether hemispheric lateralization is based on higher-level prosodic representations or lower-level encoding of acoustic cues, or both. A cross-language (Chinese; English) fMRI study was conducted to examine brain activity elicited by selective attention to Chinese intonation (I) and tone (T) presented in three-syllable (I3, T3) and one-syllable (I1, T1) utterance pairs in a speeded response, discrimination paradigm. The Chinese group exhibited greater activity than the English in a left inferior parietal region across tasks (I1, I3, T1, T3). Only the Chinese group exhibited a leftward asymmetry in inferior parietal and posterior superior temporal (I1, I3, T1, T3), anterior temporal (I1, I3, T1, T3), and frontopolar (I1, I3) regions. Both language groups shared a rightward asymmetry in the mid portions of the superior temporal sulcus and middle frontal gyrus irrespective of prosodic unit or temporal interval. Hemispheric laterality effects enable us to distinguish brain activity associated with higher-order prosodic representations in the Chinese group from that associated with lower-level acoustic/auditory processes that are shared among listeners regardless of language experience. Lateralization is influenced by language experience that shapes the internal prosodic representation of an external auditory signal. We propose that speech prosody perception is mediated primarily by the RH, but is left-lateralized to task-dependent regions when language processing is required beyond the auditory analysis of the complex sound.     

Coordination exercise and postural stability in elderly people: Effect of Tai Chi Chuan

OBJECTIVE: To evaluate the effects of coordination exercise on postural stability in older individuals by Chinese shadow boxing, Tai Chi Chuan (TCC). DESIGN: Cross-sectional study. SETTING: Research project in a hospital-based biomechanical laboratory. PARTICIPANTS: The TCC group (n = 25) had been practicing TCC regularly for 2 to 35 years. The control group (n = 14) included healthy and active older subjects. INTERVENTION: Static postural stability test: progressively harder sequential tests with 6 combinations of vision (eyes open, eyes closed, sway-referenced) and support (fixed, sway-referenced); and dynamic balance test: 3 tests of weight shifting (left to right, forward-backward, multidirectional) at 3 speeds. MAIN OUTCOME MEASURES: Static and dynamic balance of Sensory Organization Testing (SOT) of the Smart Balance Master System. RESULTS: In static postural control, the results showed no differences between the TCC or control group in the more simple conditions, but in the more complicated SOT (eyes closed with sway surface, sway vision with sway surface), the TCC group had significantly better results than the control group. The TCC group also had significantly better results in the rhythmic forward-backward weight-shifting test. Duration of practice did not seem to affect the stability of elder people. CONCLUSION: The elderly people who regularly practiced TCC showed better postural stability in the more challenged conditions than those who do not (eg, the condition with simultaneous disturbance of vision and proprioception). TCC as a coordination exercise may reduce the risk of a fall through maintaining the ability of posture control.     

Recombinant human ADAMTS13 treatment and anti‐NET strategies enhance skin allograft survival in mice

Enhancing skin allograft longevity lessens the need for new allografts before optimal intervention is available. Reduced activity of ADAMTS13 (an enzyme that cleaves the pro‐thrombotic and proinflammatory von Willebrand factor) and presence of neutrophil extracellular traps (NETs) have been implicated in liver and lung allograft failures. The effect of ADAMTS13 treatment and the impact of NETs on skin allografts, however, remain unexplored. Here, we adopted a murine model of complete mismatch full‐thickness skin transplant by grafting dorsal skin from BALB/c mice to C57BL/6J background mice. Recombinant human ADAMTS13 (rhADAMTS13) treatment of graft recipients increased allograft survival. Western blot and immunofluorescence microscopy revealed the presence of NETs in allografts of vehicle, but surprisingly, not in rhADAMTS13‐treated mice, 3 days after surgery. Recapitulating the observations in mice, NETs were also observed in all the examined allografts from burn patients. Intriguingly, knocking out peptidylarginine deiminase 4 (PAD4, a key enzyme for NET formation) or DNase 1 treatment (which cleaves NETs) also prolonged allograft survival. In summary, rhADAMTS13 lessens inflammation in allografts by reducing NET burden, resulting in enhanced allograft survival. RhADAMTS13 and anti‐NET treatments could be new therapeutic strategies to promote skin allograft longevity and, hence, the survival of patients with severe burns.     

Donor‐specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Cell therapy with autologous donor‐specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor‐specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR‐Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor‐specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts. Tregs expressing an irrelevant or anti‐HLA‐A2‐specific CAR were administered to Bl/6 mice at the time of transplanting an HLA‐A2⁺ Bl/6 skin graft. Donor‐specific CAR‐Tregs, but not irrelevant‐CAR Tregs, significantly delayed skin rejection and diminished donor‐specific antibodies (DSAs) and frequencies of DSA‐secreting B cells. Donor‐specific CAR‐Treg–treated mice also had a weaker recall DSA response, but normal responses to an irrelevant antigen, demonstrating antigen‐specific suppression. When donor‐specific CAR Tregs were tested in HLA‐A2‐sensitized mice, they were unable to delay allograft rejection or diminish DSAs. The finding that donor‐specific CAR‐Tregs restrain de novo but not memory alloreactivity has important implications for their use as an adoptive cell therapy in transplantation.