The Importance of Understanding Individual Differences of Emotion Regulation Abilities in 22q11.2 Deletion Syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterised by a complex behavioural phenotype including anxiety, attention-deficit/hyperactivity disorder and psychosis. In the current study, we aimed at improving our understanding of the heterogeneity of behavioural characteristics in a group of 129 young people (aged 4-22) with a confirmed 22q11.2 microdeletion and 116 age and gender matched typically developing controls. Half the participants with 22q11DS had behaviour characterised by emotion dysregulation. A cluster analyses, of the participants with 22q11DS, revealed four groups characterised by intact emotion regulation; predominantly internalizing problems; both internalizing and externalizing problems; and predominantly externalizing difficulties. Importantly, it was found that young people with 22q11DS whose emotion dysregulation was characterised by externalizing problems had the poorest levels of functioning. As our understanding of 22q11DS improves, it is becoming increasingly clear that we need a better understanding of how individual differences and psychosocial factors contribute to, and interact with one another, to result in the observable individual differences in the 22q11DS behavioural phenotype.

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.

The effects of FK506 on retinal ganglion cells after optic nerve crush.

PURPOSE: The purpose of this study was twofold: to determine whether immunophilins were present in the rat retina and to determine the physiologic consequence of their presence. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed on rat retinal tissue, and the immunophilin FKBP12 was found to be present in retina. Immunohistochemical studies showed the presence of FKBP12 in retinal ganglion cells (RGCs). In rats, optic nerve crush was performed on one side and a sham operation on the other side. By gavage, animals were given 5 mg/kg per day of the FKBP12 ligand FK506 in sterile phosphate-buffered saline (PBS) or in PBS alone. Eight days after nerve crush, the total number of back-labeled RGCs was estimated from retinal wholemounts. RESULTS: In control eyes, the number of labeled ganglion cells was 74,104 +/- 4,166 (mean +/- SEM) in rats receiving vehicle and 74,993 +/- 3,098 in animals receiving FK506 daily. Eight days after optic nerve crush, 27,775 +/- 3,332 labeled ganglion cells were counted in retinas of animals receiving vehicle (n = 11), whereas 33% more ganglion cells (37,118 +/- 2,475) were counted in animals receiving FK506 daily (n = 11). This difference was statistically significant (P < 0.05). CONCLUSIONS: The data presented demonstrate that the immunophilin FKBP12 is present in retina and specifically in RGCs. In addition, the FKBP12 ligand FK506 confers neuroprotection on RGCs after optic nerve crush. This neuroprotection may occur as a result of FK506's ability to interfere with apoptotic mechanisms after optic nerve crush.

Hormone replacement therapy and lens opacities: the Salisbury Eye Evaluation project.

BACKGROUND: Data suggest a possible protective effect against lens opacity with use of hormone replacement therapy (HRT). However, no agreement exists on which opacity type is affected, and more exploration of the additional role of endogenous estrogen exposure is warranted. OBJECTIVE: To determine whether HRT and the prevalence of different lens opacity types are associated after controlling for endogenous estrogen exposure. DESIGN AND SETTING: Salisbury Eye Evaluation population-based prevalence survey of residents in an eastern US city. PARTICIPANTS: One thousand two hundred thirty-nine women aged 65 through 84 years. MAIN OUTCOME MEASURES: Nuclear, cortical, and posterior subcapsular opacity. RESULTS: We found a protective association between nuclear opacity and current (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.7) and recent (OR, 0.4; 95% CI, 0.3-0.7) HRT use. Increasing number of births in younger women was also protective (test of trend, P =.05). Past HRT use protected against nuclear opacity only in women who had never been pregnant (OR, 0.2; 95% CI, 0.1-0.7). Past (OR, 0.2; 95% CI, 0.1-0.7) and current (OR, 0.3; 95% CI, 0.1-0.9) HRT use were associated with a lower prevalence of posterior subcapsular opacity. CONCLUSION: A protective association between the use of HRT and nuclear and posterior subcapsular opacities is reported, which should be confirmed in prospective studies.

Lidocaine toxicity to rat retinal ganglion cells.

PURPOSE: To examine the effects of the local anesthetic, lidocaine, on rat retinal ganglion cells (RGC) in vitro and in a modified in vivo assay. METHODS: For in vitro experiments, RGC were dissociated from freshly harvested Long Evan's rat pup retinas. The RGC were incubated overnight with varying concentrations of lidocaine (0.5-12.0 mM). Surviving cells were assayed at 24 hours. In an in vivo assay, 7-day-old Long-Evans rat pups were anesthetized and 2 microl of lidocaine (final intraocular concentration: 0.03-15 mM) or vehicle was injected intravitreally. Intravitreal coinjection of nimodipine or MK801 (dizocilpine) were also performed in a subset of animals. A week after injection, rat pups were sacrificed and each retina removed, dissociated and plated separately. RGC survival was immediately assessed. Living RGC were identified on the basis of morphology and counted in a masked fashion. RESULTS: Lidocaine is toxic in a dose dependent fashion to RGC in vitro. Lower concentrations (0.5 mM and 1.0 mM) were non-toxic; 2.0, 6.0 and 12.0 mM lidocaine killed 25%, 88% and 99% of the RGC respectively. Intravitreal lidocaine was also toxic to RGC in a dose dependent fashion. Lidocaine concentrations of 3.0 mM, 7.5 mM and 15 mM killed 25%, 38% and 44% of the RGC. This effect was blocked by the simultaneous administration of either nimodipine or MK801. CONCLUSIONS: Lidocaine is toxic to RGC both in vitro and in vivo. This effect is blocked in vivo by the simultaneous administration of agents known to block glutamate mediated neuronal death, suggesting that excitotoxicity may be involved in this process.