CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy.

We demonstrate autosomal-recessive Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in a patient with relapsing C. albicans meningoencephalitis. We identified a novel, hypomorphic mutation with intact Th17 responses, but impaired GM-CSF responses. We report complete clinical remission with adjunctive GM-CSF therapy, suggesting that a CARD9/GM-CSF axis contributes to susceptibility to candidiasis.

Establishment of motor neuron-V3 interneuron progenitor domain boundary in ventral spinal cord requires Groucho-mediated transcriptional corepression.

BACKGROUND: Dorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types. This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of split (TLE) proteins are transcriptional corepressors suggested to be recruited by at least certain Sonic hedgehog-controlled transcription factors to mediate the formation of spatially distinct progenitor domains within the ventral spinal cord. The aim of this study was to characterize the involvement of TLE in mechanisms regulating the establishment of the boundary between the most ventral spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we also examined the involvement of TLE in the acquisition of these neuronal fates. METHODOLOGY AND PRINCIPAL FINDINGS: A combination of in vivo loss- and gain-of-function studies in the developing chick spinal cord was performed to characterize the role of TLE in ventral progenitor domain formation. It is shown here that TLE overexpression causes increased numbers of p3 progenitors and promotes the V3 interneuron fate while suppressing the motor neuron fate. Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors and postmitotic motor neurons. CONCLUSION: Based on these results, we propose that TLE is important to promote the formation of the p3 domain and subsequent generation of V3 interneurons.

A controlled evaluation of a prison-based sexual offender intervention program.

The effectiveness of a prison-based cognitive behavioral program designed to modify psychological risk factors associated with sexual offending was evaluated. The Irish Prison Service Sexual Offender Intervention Programme, is a manualized 10-month Cognitive Behaviour Therapy [CBT] program involving three 2-hour group sessions per week, which are facilitated by a team of clinical psychologists and probation officers. Improvements in 38 consecutive referrals to the program were compared with the status of 38 untreated offenders who were similar in marital status, age when they left school, occupational status prior to imprisonment, offence type, presence of previous convictions, and current sentence length. All research participants completed the same assessment protocol, which evaluated psychological factors associated with sexual offending at times equivalent to pre- and postintervention. Compared with the untreated control group, program participants showed statistically significant improvement on some but not all self-report measures of cognitive distortions, empathy, interpersonal skills, self-regulation, and relapse prevention. Motivation to change among the untreated control group was not associated with change in psychological functioning in the absence of the assistance of the treatment program. Implications for sexual offender intervention delivery are considered.

Attachment styles and psychological profiles of child sex offenders in Ireland.

When 29 child sex offenders, 30 violent offenders, 30 nonviolent offenders, and 30 community controls were compared, a secure adult attachment style was 4 times less common in the child sex offender group than in any of the other three groups. Ninety-three percent of sex offenders had an insecure adult attachment style. Compared with community controls, the child sex offender group reported significantly lower levels of maternal and paternal care and significantly higher levels of maternal and paternal overprotection during their childhood. Compared with all three comparison groups, the child sexual offenders reported significantly more emotional loneliness and a more external locus of control. With respect to anger management, the child sexual offenders' profile more closely approximated those of nonviolent offenders and community controls than that of violent offenders.