Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

Being in charge: Older women and their younger female kin

Our cross-cultural study of the relationship between older women and their younger female kin examines women's hierarchies based on age and focuses on the exercise of authority by women, when such authority is traditional and accepted. Data were collected for two world-wide samples each consisting of 30 societies, varying in complexity, subsistence base, geographic location, and in customs related to women's lives. Three hypotheses were tested. The findings, which are statistically significant, suggest that the relationships between older women and their younger female kin are patterned and predictable, determined by the role of women in subsistence activities, by rules for post-marital residence, and by descent.When domination can only be exercised... directly, between one person and another, it can not take place overtly and must be disguised under the veil of enchanted relationships, the official model of which is presented by the relations between kinsmen.The gentle, invisible form of violence, which is never recognized as such... can not fail to be seen as the most economical mode of domination...The system is such that the dominant agents have a vested interest in virtue. (Bourdieu 1991191, 192, 194)     

Serotonergic mechanisms of cocaine effects in humans

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine high were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.     

Potential of Gene Therapy in Bone Marrow Transplantation

Gene therapy, initiated as a treatment for inherited disorders such as adenosine deaminase deficiency, is now a promising therapeutic strategy for malignancies and other acquired diseases. In particular, in the field of bone marrow transplantation (BMT) for haematological malignancies, the gene transfer of the suicide gene HSV-TK into donor lymphocytes allows control of the severe complication graft-versus-host disease (GvHD). The transfer of the HSV-TK suicide gene confers selective sensitivity to the drug ganciclovir, allowing in vivo elimination of the donor T-cells if severe GvHD occurs. In Italy, the first pilot study on delayed infusion of genetically engineered donor lymphocytes after T-depleted allogeneic BMT documented efficacy of engineered donor lymphocytes in terms of anti-tumour activity and efficiency of the suicide system. GvHD developed in 3 out of 8 patients and was successfully treated by ganciclovir administration.     

Spontaneous and induced recovery of visual hemineglect during cooling inactivation of middle suprasylvian cortex in the cat

The purpose of the present study was to observe recovery of orienting deficits during unilateral and bilateral cooling inactivation of the middle suprasylvian (MS) cortex. Unilateral MS cooling resulted in a contralateral hemineglect (no orienting responses towards stimuli in the contracooled hemifield) that spontaneously recovered within less than 40 min of continued cooling. Moreover, the brain changes responsible for this recovery were partially retained and cumulated over successive cooling days. Bilateral MS cooling indicated that recovery of neglect can be induced by a restoration of the imbalance between activity levels of structures in both hemispheres and revealed an interaction between spontaneous and induced recovery of neglect. These results show that considerable changes may occur in the brain during cooling for rather short periods. Possible explanations for these changes are discussed.     

Age but not sex affects motor recovery after unilateral sensorimotor cortex suction-ablation in the rat

Both age and sex can influence recovery after brain injury. To determine the impact of these variables on motor recovery, young (2 month old) and older (5-6 months old) male and female rats were first trained to traverse a narrow elevated beam. Rats then underwent suction-ablation of right sensorimotor cortex or sham operation. Motor recovery was measured by repeated testing on the beam over 3 weeks. Shamoperated rats performed perfectly regardless of age or sex throughout testing. There was no difference in beam-walking scores among the groups of lesioned rats on the first trial 24 hrs. after injury (Kruskal-Wallis H = 0.18, p = 0.98). There was a significant effect of age (two-way ANOVA F1,32 = 29.58, p < 0.0001) but not sex (ANOVA F1,32 = 0.78, p = 0.38) on subsequent recovery. These data show that motor recovery after unilateral injury to the sensorimotor cortex varies with age, but not sex.     

Prospective study design for the Heidelberg retina tomograph: the effect of change in focus setting

Background: Image scaling on the Heidelberg Retina Tomograph (HRT) is based on an axial model of ametropia. In the longitudinal follow-up of patients, refractive changes in ametropia may occur; the HRT interprets such change as being axial in origin. This results in an apparent alteration in the size of fundus features with time and in reduced sensitivity of the instrument to subtle changes relating to disease progression. The aim of this study was to determine the effect of changing HRT focus settings on the absolute scaling of topography images. Methods: Seven image series were acquired of the optic nerve head of a single emmetropic eye at each of a range of panel focus settings under three conditions: (A) emmetropia, (B) trial lens-induced ametropia, (C) contact lens-induced ametropia. A masked observer measured the separation between two defined retinal vascular bifurcations for each topography image. bb Results: The measured distance decreased with a positive shift in focus. There was a significant difference in distance with change in focus setting for all conditions (A P<0.008, B and C P<0.0001). Over equivalent focus ranges, data from the three groups were not significantly different, lying within the 95% confidence limits at each setting. The mean standard deviation for the distance measure was 10 m. Conclusion: Adjustment in focus settings to compensate for refractive change in eyes of stable axial length and keratometry induces a change in the topography measures using the HRT. It is recommended that, for the detection of subtle change over time, refractive changes are corrected without a change in the panel focus setting.     

Testing the reliability of a new measure of life events and experiences in childhood: The Psychosocial Assessment of Childhood Experiences (PACE)

There are few well validated instruments for measuring the impact of life events and experiences in childhood and adolescence. This study examines the reliability of a new instrument, the Psychosocial Assessment of Childhood Experiences of PACE. Fifteen children and parents were interviewed on two cassions ten days apart for the main test-retest reliability study. About half of the events recorded were reported on both occasions (0.45% and 0.55% concordance). When the impact of specific events was examined much higher levels of agreement were found. Inter-rater reliability tests also yielded higher rate (Kappa 0.74 and above). Possible reasons for these important differences are discussed and the inherent methodological difficulties considered.

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Zusammenfassung Es existieren nur wenige gut validierte Meßinstrumente zur Erfassung von Lebensereignissen und Erfahrungen im Kindes- und Jugendalter. Diese Studie untersucht die Reliabilität eines neuen Verfahrens, des Psychosocial Assessment of Childhood Experiences oder PACE. 15 Kinder und Elternteile wurden zweimal im Abstand von 10 Tagen für die Überprüfung der Haupttest-Retest-Reliabilität interviewt. Ca. die Hälfte aller Ereignisse, die beim Interview berichtet wurden, wurdem beim Zweitinterview ebenfalls angegeben (Konkordanzen 0,45 und 0.55). Deutlich höhere Übereinstimmungen fanden sich bei Untersuchung der Auswirkungen spezifischer Ereignisse. Die Inter-Rater-Reliabilitätstests ergaben ebenfalls höhere Werte (Kappa 0.74). Mögliche Ursachen dieser wichtigen Unterschiede werden unter Berücksichtigung der inhärenten methodischen Schwierigkeiten diskutiert.

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Résumé II y a peu d'instruments correctement validés de mesures de l'impact des événements de vie des expériences dans l'enfance et l'adolescence. Cette étude examine la fiabilité d'un nouvel instrument, l'évaluation psycho-sociale des expériences infantiles (Psychosocial Assessment of Childhood Experiences ou PACE). 15 enfants et parents furent interrogés à deux reprises à 10 jours d'intervalle pour evaluer la fiabilité test-retest. Environ la moitié des événements rapportés le furent dans les deux occasions (0.45% et 0.55% de concordance). Quand l'impact des événements déviés spécifiques fut étudié un niveau plus élevé de concordance fut trouvé. La fidélité inter-cotateurs des tests obtinet également des taux plus élevés (kappa 0.74 et audessus). Les raisons possibles de ces différences sont discutées et les difficultés méthodologiques inhérentes prises en compte.