Conscious and subliminal conflicts in normal subjects and patients with schizophrenia: the role of the anterior cingulate

The human anterior cingulate cortex (ACC), which is active during conflict-monitoring tasks, is thought to participate with prefrontal cortices in a distributed network for conscious self-regulation. This hypothesis predicts that conflict-related ACC activation should occur only when the conflicting stimuli are consciously perceived. To dissociate conflict from consciousness, we measured the behavioral and brain imaging correlates of a motor conflict induced by task-irrelevant subliminal or conscious primes. The same task was studied in normal subjects and in patients with schizophrenia in whom the ACC and prefrontal cortex are thought to be dysfunctional. Conscious, but not subliminal, conflict affected anterior cingulate activity in normal subjects. Furthermore, patients with schizophrenia, who exhibited a hypoactivation of the ACC and other frontal, temporal, hippocampal, and striatal sites, showed impaired conscious priming but normal subliminal priming. Those findings suggest that subliminal conflicts are resolved without ACC contribution and that the ACC participates in a distributed conscious control network that is altered in schizophrenia.     

Genetic specificity of a plant–insect food web: Implications for linking genetic variation to network complexity

Theory predicts that intraspecific genetic variation can increase the complexity of an ecological network. To date, however, we are lacking empirical knowledge of the extent to which genetic variation determines the assembly of ecological networks, as well as how the gain or loss of genetic variation will affect network structure. To address this knowledge gap, we used a common garden experiment to quantify the extent to which heritable trait variation in a host plant determines the assembly of its associated insect food web (network of trophic interactions). We then used a resampling procedure to simulate the additive effects of genetic variation on overall food-web complexity. We found that trait variation among host-plant genotypes was associated with resistance to insect herbivores, which indirectly affected interactions between herbivores and their insect parasitoids. Direct and indirect genetic effects resulted in distinct compositions of trophic interactions associated with each host-plant genotype. Moreover, our simulations suggest that food-web complexity would increase by 20% over the range of genetic variation in the experimental population of host plants. Taken together, our results indicate that intraspecific genetic variation can play a key role in structuring ecological networks, which may in turn affect network persistence.Network theory has provided both a conceptual and a quantitative approach for mapping interactions between species and making predictions about how the gain or loss of species will affect the structure and dynamics of ecological networks (1–3). Representing a network at the species level, however, makes the implicit assumption that each species consists of a homogenous population of individuals, all of which interact equally with individuals of different species. However, most populations are heterogeneous mixtures of individuals that vary in their phenotypes, and there is growing evidence that this intraspecific variation is an important factor governing the assembly of ecological communities (4–6). Consequently, there is a clear need to account for the role of intraspecific variation in structuring ecological networks (7).Genetic variation is a key driver of intraspecific variation and many studies have now demonstrated direct and indirect genetic effects on species interactions (8–10) and the composition of communities across multiple trophic levels (11–14). This prior work forms a clear expectation that intraspecific genetic variation is capable of scaling up to affect the structure of an ecological network. In particular, we expect that network structure will be affected by genetic variation through at least two different mechanisms. For a food web (network of trophic interactions), genetic variation in the quality of a basal resource may alter the (i) abundances or (ii) phenotypes of consumer species or both (15). These direct genetic effects on consumers may then have cascading effects on the strength of trophic interactions between consumers and their predators (15), resulting in distinct compositions of trophic interactions associated with different genotypes of the basal resource (Fig. 1). If such genetic specificity in the composition of trophic interactions occurs, then theory predicts that increasing genetic variation will result in more interactions per species (6, 16) and therefore greater food-web complexity (Fig. 2). Moreover, greater complexity may in turn affect food-web dynamics, as more complex food webs are predicted to be more robust to species extinctions (3, 17). However, whether genetic variation is capable of scaling up to affect food-web complexity is currently unclear.Open in a separate windowFig. 1.Genetic specificity of trophic interactions in a plant–insect food web. The species comprising the food web in this study include a host plant (coastal willow, S. hookeriana), four herbivorous galling insects, and six insect parasitoids (species details in Materials and Methods). The plant–insect food web consists of 16 trophic interactions (4 willow–gall and 12 gall–parasitoid) aggregated from all plant individuals sampled in this common garden experiment, whereas each genotype subweb represents the trophic interactions aggregated from all plant individuals of the corresponding genotype. We depicted three genotype subwebs (of 26) to illustrate the differences in trophic interactions associated with each willow genotype. The width of each gray segment is proportional to the number of individuals associated with each trophic interaction. Note that we scaled the width of trophic interactions to be comparable among genotype subwebs, but not between subwebs and the aggregated food web, to emphasize the differences among subwebs.Open in a separate windowFig. 2.Conceptual model of how increasing genetic variation (number of shades of green circles) results in greater food-web complexity (number of interactions per species). If different genotypes of a basal resource are associated with distinct compositions of trophic interactions (i.e., genetic specificity of trophic interactions), then increasing genetic variation in the resource will result in a more complex food web because of the increase in the number of interactions per species at all three trophic levels. Colors correspond to different trophic levels (green, basal resource; blue, primary consumer; orange, secondary consumer), whereas different shapes within each trophic level correspond to different species.In this study, we quantify the genetic specificity of trophic interactions and use these data to simulate the additive effects of genetic variation on food-web complexity. To do this, we used a common garden experiment of a host plant (26 genotypes of coastal willow, Salix hookeriana) and its associated food web of insect galls and parasitoids (Fig. 1). We focused on this plant–insect food web for three reasons. First, we have demonstrated in previous work that S. hookeriana (hereafter, willow) displays heritable variation in traits associated with leaf quality (36 traits, mean H² = 0.72) and plant architecture (4 traits, mean H² = 0.27), some of which are also associated with resistance to its community of galling herbivores (18). Second, the unique biology of galling insects makes them ideal for building quantitative food webs. In particular, galls provide a refuge for larva from attack by most generalist predators (19); therefore, galls and their natural enemies often form a distinct subset of the larger food web associated with host plants. In our system, all of the natural enemies are insect parasitoids that complete their development within the gall after parasitizing larva, making it easy to identify and quantify all of the trophic interactions within this food web. Third, the biology of galls is also ideal for identifying the mechanisms mediating trophic interactions. In particular, gall size is a key trait that affects the ability of parasitoids to successfully oviposit through the gall wall and into the larva within the gall (i.e., larger galls provide a refuge from parasitism) (20). Moreover, gall size is determined, in part, by the genotype of the plant (20), so we have a clear mechanism by which genetic variation can affect the strength of trophic interactions. Taken together, our study seeks to examine how intraspecific genetic variation influences the structure of ecological networks. In doing so, our study takes a crucial step toward a more predictive understanding of how the gain or loss of genetic variation will affect the dynamics of ecological networks.     

Diastolic asynchrony is more frequent than systolic asynchrony in dilated cardiomyopathy and is less improved by cardiac resynchronization therapy.

OBJECTIVES: To compare the incidence of diastolic and systolic asynchrony, assessed by tissue Doppler imaging (TDI), in patients with congestive heart failure (CHF) and severe left ventricular (LV) dysfunction, and to assess TDI changes induced by cardiac resynchronization therapy (CRT). BACKGROUND: Thirty percent of CRT candidates are nonresponders. Besides QRS width, the presence of echographic systolic asynchrony has been used to identify future responders. Little is known about diastolic asynchrony and its change after CRT. METHODS: Tissue Doppler imaging was performed in 116 CHF patients (LV ejection fraction 26 +/- 8%). Systolic and diastolic asynchrony was calculated using TDI recordings of right ventricular and LV walls. RESULTS: The CHF group consisted of 116 patients. Diastolic asynchrony was more frequent than systolic, concerning both intraventricular (58% vs. 47%; p = 0.0004) and interventricular (72 vs. 45%; p < 0.0001) asynchrony. Systolic and diastolic asynchrony were both present in 41% patients, but one-third had isolated diastolic asynchrony. Although diastolic delays increased with QRS duration, 42% patients with narrow QRS presented with diastolic asynchrony. Conversely, 27% patients with large QRS had no diastolic asynchrony. Forty-two patients underwent CRT. Incidence of systolic intraventricular asynchrony decreased from 71% to 33% after CRT (p < 0.0001), but diastolic asynchrony decreased only from 81% to 55% (p < 0.0002). Cardiac resynchronization therapy induced new diastolic asynchrony in eight patients. CONCLUSIONS: Diastolic asynchrony is weakly correlated with QRS duration, is more frequent than systolic asynchrony, and may be observed alone. Diastolic asynchrony is less improved by CRT than systolic. Persistent diastolic asynchrony may explain some cases of lack of improvement after CRT despite good systolic resynchronization.     

Colonoscopy of acute colitis

Complications that might lead to surgery in severe attacks of ulcerative colitis have been found to be correlated with the depth of colonic ulcerations as measured by pathological examination of colectomy specimens. In order to evaluate the value of colonoscopy for the assessment of colonic ulcerations, we have reviewed the clinical, biological, colonoscopic, and anatomical findings in 85 consecutive patients with attacks of ulcerative colitis involving at least the rectosigmoid and part of the descending colon, seen in our center between 1981 and 1989. All had colonoscopy performed by a senior endoscopist at entry. Extensive deep colonic ulcerations were diagnosed in 46 of them, and moderate endoscopic colitis in 39. No complication related to colonoscopy occurred except for one colonic dilatation. Forty-three of the 46 patients with severe endoscopic colitis were operated upon: 38 of them failed to improve with high-dose corticosteroids and five had a toxic megacolon. Extensive ulcerations reaching at least the circular muscle layer were found at pathological examination of colectomy specimen in 42 of the 43 patients. Conversely, 30 of 39 patients with moderate endoscopic colitis went into clinical remission with medical treatment, and only nine patients needed further surgery because of medical treatment failure. Six of these nine patients underwent another colonoscopy prior to colectomy, and all six showed features of severe endoscopic colitis. Deep ulcerations reaching the circular muscle layer were found at pathological examination in five of these six patients and in one additional patient whose colonoscopy had been performed 21 days before colectomy. We conclude that, in expert hands, colonoscopy is safe and accurately selects patients with high risk of surgical complications who need early surgery in case of failure of medical treatment.     

Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.     

Practices and opinions regarding HPV vaccination among French general practitioners: evaluation through two cross-sectional studies in 2007 and 2010

Objectives

To use both quantitative and qualitative methods to investigate the evolution of practices and opinions regarding human papillomavirus (HPV) vaccination among French general practitioners.

Methods

A cross-sectional study (self-questionnaires) was performed in 2007 and repeated in 2010 among 271 general practitioners. Semi-structured interviews were conducted on 27 voluntary participants by a sociologist and analyzed according to content analysis.

Results

Acceptability of HPV vaccination had increased from 2007 to 2010 (79.9 vs. 87.1 %, respectively), just as the practice of HPV vaccination among 14-year-old girls (19.0 vs. 49.1 %, respectively). Though about 60 % reported complications associated with HPV vaccination, irrespective of year, the types of difficulties have varied: difficulties related to “questions asked by patients” had decreased, though concerns about side effects had remained stable. During interviews, difficulties related to “the reason for medical consultation” and “the target age” were often associated with addressing the issue of sexuality, especially when the parents were present.

Conclusions

Although the high level of acceptability of HPV vaccination among general practitioners, which increased from 2007 to 2010, there remain difficulties in addressing this practice.     

Intravenous Immunoglobulin and Rituximab for Cerebellar Ataxia with Glutamic Acid Decarboxylase Autoantibodies

Cerebellar ataxia associated with glutamic acid decarboxylase autoantibodies (GAD-ab) is a rare and usually slow progressive disease with moderate to severe gait and limb ataxia, dysarthria, and nystagmus. The treatment for this condition is still being discussed. We report the cases of three patients with GAD-ab cerebellar ataxia treated successively with intravenous immunoglobulin (IVIg) and rituximab. Symptoms improved in one case after rituximab therapy and were stabilized in another after a combined therapy of IVIg and rituximab. The third patient continued to worsen despite these treatments. We conclude that IVIg and rituximab therapy could improve or stabilize GAD-ab cerebellar ataxia. Early treatment, the lack of cerebellar atrophy on magnetic resonance imaging, and a subacute onset of the symptoms could be decisive prognostic factors.     

Get Screened: A Randomized Trial of the Incremental Benefits of Reminders, Recall, and Outreach on Cancer Screening

BACKGROUND

Rates of breast cancer (BC) and colorectal cancer (CRC) screening are particularly low among poor and minority patients. Multifaceted interventions have been shown to improve cancer-screening rates, yet the relative impact of the specific components of these interventions has not been assessed. Identifying the specific components necessary to improve cancer-screening rates is critical to tailor interventions in resource limited environments.

OBJECTIVE

To assess the relative impact of various components of the reminder, recall, and outreach (RRO) model on BC and CRC screening rates within a safety net practice.

DESIGN

Pragmatic randomized trial.

PARTICIPANTS

Men and women aged 50–74 years past due for CRC screen and women aged 40–74 years past due for BC screening.

INTERVENTIONS

We randomized 1,008 patients to one of four groups: (1) reminder letter; (2) letter and automated telephone message (Letter + Autodial); (3) letter, automated telephone message, and point of service prompt (Letter + Autodial + Prompt); or (4) letter and personal telephone call (Letter + Personal Call).

MAIN MEASURES

Documentation of mammography or colorectal cancer screening at 52 weeks following randomization.

KEY RESULTS

Compared to a reminder letter alone, Letter + Personal Call was more effective at improving screening rates for BC (17.8 % vs. 27.5 %; AOR 2.2, 95 % CI 1.2–4.0) and CRC screening (12.2 % vs. 21.5 %; AOR 2.0, 95 % CI 1.1–3.9). Compared to letter alone, a Letter + Autodial + Prompt was also more effective at improving rates of BC screening (17.8 % vs. 28.2 %; AOR 2.1, 95 % CI 1.1–3.7) and CRC screening (12.2 % vs. 19.6 %; AOR 1.9, 95 % CI 1.0–3.7). Letter + Autodial was not more effective than a letter alone at improving screening rates.

CONCLUSIONS

The addition of a personal telephone call or a patient-specific provider prompt were both more effective at improving mammogram and CRC screening rates compared to a reminder letter alone. The use of automated telephone calls, however, did not provide any incremental benefit to a reminder letter alone.