Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study

The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder

Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

OBJECTIVE: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. METHODS: Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. RESULTS: 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = -0.91; p<0.001). CONCLUSION: During 2004-2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes

The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3)

ObjectiveTo determine if the need for mechanical ventilation alters the association between prolonged patent ductus arteriosus (PDA) exposure and bronchopulmonary dysplasia (grades 2 and 3) (BPD).Study designObservational study of 407 infants (&lt;28 weeks' gestation) with echocardiograms performed at planned intervals.ResultsTwelve percent (48/407) of study infants had BPD (grades 2 and 3). In a multivariable regression model, exposure to a moderate-to-large PDA shunt for ≥7 days was associated with an increased risk of BPD (grades 2 and 3) (from 16 to 35%: aRD = 19% (6, 32%), p &lt; 0.005) when infants required ≥10 days of intubation (n = 170). In contrast, there was no significant association between prolonged PDA exposure and BPD when infants required ≤9 days of intubation (aRD = 4%) (-1, 10%) (n = 237).ConclusionsModerate-to-large PDAs are associated with an increased risk of BPD-but only when infants require intubation ≥10 days

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis.

ObjectiveTo examine the relationship between intestinal perforations (caused by either spontaneous perforation (SIP) or necrotizing enterocolitis (NEC)) and the outcome "death due to intestinal perforation".MethodsMultivariable logistic regression analyses were used to compare infants &lt;28 weeks' gestation with SIP (n = 32) and perforated-NEC (n = 45) for the outcome perforation-related death.ResultsIn univariate analyses the incidence of death due to perforation was higher among infants with perforated-NEC (36%) than infants with SIP (13%). However, infants with perforated-NEC were more likely to be older than 10 days and have bacteremia/fungemia with non-coagulase-negative staphylococci (non-CONS) organisms than infants with SIP. After adjusting for confounding the only variable that was significantly associated with mortality due to perforation was the presence of non-CONS bacteremia/fungemia at the onset of perforation.ConclusionsThe apparent association between death and perforated-NEC could be explained by the higher incidence of non-CONS bacteremia/fungemia among infants with perforated-NEC