Social and emotional processing in Prader-Willi syndrome: genetic subtype differences

Background

People with Prader-Willi syndrome (PWS) demonstrate social dysfunction and increased risk of autism spectrum disorder, especially those with the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype. This study compared the neural processing of social (faces) and nonsocial stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents and adults with PWS.

Methods

Upright and inverted faces, and nonsocial objects with positive and negative emotional valence were presented to participants with PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and event-related potential (ERP) data were recorded.

Results

There were no genetic subtype group differences in accuracy, and all participants performed above chance level. ERP responses revealed genetic subtype differences in face versus object processing. In those with deletions, the face-specific posterior N170 response varied in size for face stimuli versus inverted faces versus nonsocial objects. Persons with mUPD generated N170 of smaller amplitude and showed no stimulus differentiation. Brain responses to emotional content did not vary by subtype. All participants elicited larger posterior and anterior late positive potential responses to positive objects than to negative objects. Emotion-related differences in response to faces were limited to inverted faces only in the form of larger anterior late positive potential amplitudes to negative emotions over the right hemisphere. Detection of the target smiling faces was evident in the increased amplitude of the frontal and central P3 responses but only for inverted smiling faces.

Conclusion

Persons with the mUPD subtype of PWS may show atypical face versus object processes, yet both subtypes demonstrated potentially altered processing, attention to and/or recognition of faces and their expressions.     

Sex dependent influence of a functional polymorphism in steroid 5‐α‐reductase type 2 (SRD5A2) on post‐traumatic stress symptoms

A non‐synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5‐α‐reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post‐traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African‐American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post‐traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex‐dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex‐specific way, the severity of post‐traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.     

A premaxilla with a supernumerary tooth indicating a developmental region with a variety of dental abnormalities: a report of nine cases

The aim of this study was to elucidate whether a premaxilla with a supernumerary tooth has additional dental abnormalities. The study does not include premaxillas with a mesiodens, only premaxillas with parasagittally located supernumerary teeth. Radiographs from eight children, followed from 1 year and 5 months to 11 years and 5 months in the municipal dental health service in Denmark, were analyzed. One patient was seen only once. Dental abnormalities recorded included: invaginations on permanent incisors, resorption of roots of incisors, curved roots of incisors, delayed eruption, and delayed formation of roots. The study shows that there are dental abnormalities within the premaxillary region where the supernumerary tooth is located. This indicates that, apart from the supernumerary tooth, a more widespread deviation from normal conditions including tooth malformation, arrested eruption, and root resorption occur within the premaxillary region. The most important outcome of this study is that in the region with a supernumerary tooth the adjacent incisor shows delayed eruption after surgical removal of the supernumerary tooth. The deviations in root morphology, including root resorption, are not limited to patients who have had orthodontic treatment, but patients who did not receive orthodontic treatment also revealed deviations in root morphology. Therefore the treatment outcome can be different from the expected outcome.     

Complications and survival rates of teeth after dental trauma over a 5-year period

Objectives

The purpose of this study was to evaluate whether the current guidelines of the International Association of Dental Traumatology (IADT) for emergency care of traumatised teeth result in lower complication rates.

Materials and methods

Therapeutic strategies of 361 dental injuries in 291 patients treated at a university dental hospital over a 5-year period were investigated by evaluating the patients' records. Adherence to the guidelines of the IADT (Flores et al. Dent Traumatol 17:1–4, 2001; 49–52, 2001; 97–102, 2001; 145–148, 2001; and 193–196, 2001; Flores et al. Dent Traumatol 23:66–71, 2007; 130–136, 2007; and 196–202, 2007) was evaluated. Complications were also recorded according to the patients' records and analysed relative to the treatment and injury pattern. During follow-up visits, the teeth were inspected regarding pulp vitality and overall function of the injured tooth. The Kaplan–Meier survival analysis of pulps and teeth was performed for different injury categories.

Results

The majority of injuries (322/361; 89.2 %) were treated according to the guidelines. When IADT guidelines were followed, complication rates were significantly lower than for cases treated without adherence to the guidelines. The most frequent complication was the loss of restoration, followed by pulp necrosis, abnormal mobility, and tooth loss. The overall survival analysis showed that in the permanent dentition, the loss of pulp vitality and tooth occurs within the first 6 months but may also occur later.

Conclusions

The results of this study indicate that traumatised teeth that were treated according to the recommendations had a lower complication rate. In addition, the majority of pulp necrosis and tooth losses in the permanent dentition occurred within the first 6 months after trauma. These results indicate that early follow-up visits are essential to promptly treat complications.

Clinical relevance

Adherence to the IADT guidelines for treatment of dental trauma may lead to more favourable outcomes when compared to cases treated without compliance to the guidelines.     

Awake craniotomies without any sedation: the awake-awake-awake technique

Background

Temporary anaesthesia or analgosedation used for awake craniotomies carry substantial risks like hemodynamic instabilities, airway obstruction, hypoventilation, nausea and vomiting, agitation, and interference with test performances. We tested the actual need for sedatives and opioids in 50 patients undergoing awake craniotomy for brain tumour resection in eloquent or motoric brain areas when cranial nerve blocks, permanent presence of a contact person, and therapeutic communication are provided.

Methods

Therapeutic communication was based on the assumption that patients in such an extreme medical situation enter a natural trance-like state with elevated suggestibility. The anaesthesiologist acted as a continuous guide, using a strong rapport, nonverbal communication, hypnotic suggestions, such as dissociation to a “safe place”, and the reframing of disturbing noises, while simultaneously avoiding negative suggestions. Analgesics or sedatives were at hand according to the principle “as much as necessary, but not more than needed”.

Results

No sedation was necessary for any of the patients besides for the treatment of seizures. Only two-thirds of the patients requested remifentanil, with a mean dosage of 96 μg before the end of tumour resection and a total of 156 μg. Hemodynamic reactions indicative of stress were mainly seen during nerve blockades and neurological testing. Postoperative vigilance tests showed equal or higher scores than preoperative tests.

Conclusions

The main challenges for patients undergoing awake craniotomies include anxiety and fears, terrifying noises and surroundings, immobility, loss of control, and the feeling of helplessness and being left alone. In such situations, psychological support might be more helpful than the pharmacological approach. With adequate therapeutic communication, patients do not require any sedation and no or only low-dose opioid treatment during awake craniotomies, leaving patients fully awake and competent during the entire surgical procedure without stress. This approach can be termed “awake-awake-awake-technique”.     

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.     

Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.