Characterization of lipid-modified immunogenic proteins of Treponema pallidum expressed in Escherichia coli

This study describes the sequence of the immunodominant Treponema pallidum surface protein TpD and its expression in Escherichia coli. The translated TpD DNA sequence revealed the presence of a putative site for lipid-modification downstream from the signal sequence of this membrane protein. Growth of TpD-expressing E. coli in the presence of radioactive palmitic acid revealed that TpD was lipid-modified. Three other, previously characterized cloned proteins of T. pallidum were also lipid-modified. The N-termini of two of three sequenced T. pallidum proteins contain a tetrapeptide sequence characteristic for lipoproteins in Gram-negative bacteria: Leu-X-Y-Cys. Only TpD differed from this consensus sequence in the substitution of the first residue by Phe. The apparent high incidence of lipoproteins among E. coli recombinants expressing T. pallidum antigens suggest an important role of lipoproteins in the induction of humoral immunity during syphilitic infection.     

Somatic symptoms,pain, catastrophizing and the association with disability among children with heritable connective tissue disorders

The aim of the present study was to investigate the nature and prevalence of nonspecific somatic symptoms, pain and catastrophizing in children with Heritable Connective Tissue Disorders (HCTD), and to determine their association with disability. This observational, multicenter study included 127 children, aged 4–18 years, with Marfan syndrome (MFS) (59%), Loeys-Dietz syndrome (LDS) (8%), Ehlers-Danlos syndromes (EDS) (12%) and hypermobile Ehlers-Danlos syndrome (hEDS) (23%). The assessments included the Children's Somatization Inventory or parent proxy (CSI, PCSI), pain visual-analogue scale (VAS), SUPERKIDZ body diagram, Pain Catastrophizing Scale Child or parent proxy (PCS-C, PCS-P) and Childhood Health Assessment Questionnaire (CHAQ-30). Data from children aged ≥8 years were compared to normative data. In children ≥ 8 years (n = 90), pain was present in 59%, with a median of 4 (IQR = 3–9) pain areas. Compared to normative data, the HCTD group reported significantly higher on the CSI (p ≤ 0.001, d = 0.85), VAS pain intensity (p ≤ 0.001, d = 1.22) and CHAQ-30 (p ≤ 0.001, d = 1.16) and lower on the PCS-C (p = 0.017, d = −0.82) and PCS-P (p ≤ 0.001, d = −0.49). The intensity of nonspecific somatic symptoms and pain explained 45% of the variance in disability (r² = 0.45 F(2,48) = 19.70, p ≤ 0.001). In children ≤ 7 years (n = 37), pain was present in 35% with a median of 5(IQR = 1–13) pain areas. The mean(SD) VAS scores for pain intensity was 1.5(2.9). Functional disability was moderately correlated to the number of pain areas (r = 0.56, p ≤ 0.001), intensity of nonspecific somatic symptoms (r = 0.63, p ≤ 0.001) and pain (r = 0.83, p ≤ 0.001). In conclusion, this study supports the need for comprehensive assessment of nonspecific somatic symptoms, pain, and disability in children with HCTD to allow tailored treatment.     

Appropriateness,diagnostic value,and outcomes of repeat testing following index echocardiography

Aims

Emergency admission to hospital is associated with an economic burden and mortality. Echocardiography is often the first‐line cardiovascular imaging investigation. Repeat testing is common; however, there are sparse data on the prevalence, appropriateness, or outcome of repeat testing.

Methods

We performed an electronic database search for patients with emergency admissions to our institution in February 2015. An electronic patient record review of inpatient echocardiograms was undertaken. Indications for echocardiography were classified as appropriate, may be appropriate, or rarely appropriate. One‐year follow‐up for repeat testing and mortality was investigated.

Results

A total of 409 of 2306 (17.7%) unplanned/emergency admissions underwent inpatient echocardiography. Abnormalities were identified in 165/409 (40.3%) of these patients; 154 of 409 (37.7%) had a repeat echocardiogram within the next year. Rarely appropriate indications for echocardiography occurred in 51 (33%) of repeat vs 53 (16%) of index echocardiograms, P < .0001. Repeat testing was associated with a change in findings in 17/154 (11%) patients overall. All of whom had an abnormal index echocardiogram and had an appropriate indication. There was no difference in mean survival time between patients who underwent repeat and those who only underwent a single index echocardiogram (310 days vs 327 days), P = .34.

Conclusion

Inpatient echocardiography in emergency hospital admissions identifies clinically important pathology. Repeated testing is common within 1 year of hospital admission. New diagnostic findings occurred in 11% of patients and only in patients with appropriate studies and an abnormal index echocardiogram. Identification of methods to reduce repeat testing and implement appropriateness criteria is warranted.     

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications

Background

Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy.

0.5 Mb Array as a First‐Line Prenatal Cytogenetic Test in Cases without Ultrasound Abnormalities and Its Implementation in Clinical Practice

Using whole‐genome array testing instead of karyotyping in prenatal diagnosis for all indications may be desirable because of the higher diagnostic yield and shorter reporting time. The goal of this research was finding the optimal array resolution that could replace routine prenatal karyotyping in cases without ultrasound abnormalities, for example, referred for advanced maternal age or abnormal first trimester screening. As variants of unknown clinical significance (VOUS), if reported, might complicate decision‐making about continuation of pregnancy, such an optimal array resolution should have a high abnormality detection rate and reveal a minimal amount of VOUS. The array data of 465 fetuses were retrospectively evaluated with several resolution levels, and the Decipher microdeletion/microduplication syndrome list was reviewed to assess what could be theoretically missed with a lower resolution. A 0.5‐Mb resolution showed a high diagnostic yield potential and significantly minimized the number of VOUS. Based on our experience, we recommend genomic SNP array as a first‐tier test in prenatal diagnosis. The resolution should be chosen based on the indication. In cases of fetal ultrasound abnormalities or intrauterine fetal death (IUFD), high‐resolution analysis should be done. In other cases, we advise replacing karyotyping by SNP array analysis with 0.5 Mb resolution.     

Behavioral activation treatments of depression: a meta-analysis

Activity scheduling is a behavioral treatment of depression in which patients learn to monitor their mood and daily activities, and how to increase the number of pleasant activities and to increase positive interactions with their environment. We conducted a meta-analysis of randomized effect studies of activity scheduling. Sixteen studies with 780 subjects were included. The pooled effect size indicating the difference between intervention and control conditions at post-test was 0.87 (95% CI: 0.60 - 1.15). This is a large effect. Heterogeneity was low in all analyses. The comparisons with other psychological treatments at post-test resulted in a non-significant pooled effect size of 0.13 in favor of activity scheduling. In ten studies activity scheduling was compared to cognitive therapy, and the pooled effect size indicating the difference between these two types of treatment was 0.02. The changes from post-test to follow-up for activity scheduling were non-significant, indicating that the benefits of the treatments were retained at follow-up. The differences between activity scheduling and cognitive therapy at follow-up were also non-significant. Activity scheduling is an attractive treatment for depression, not only because it is relatively uncomplicated, time-efficient and does not require complex skills from patients or therapist, but also because this meta-analysis found clear indications that it is effective.     

Disruption of structural and functional networks in long‐standing multiple sclerosis

Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter morphology and functional coactivation. We investigated, how gray matter and functional networks were affected within the same MS sample and examined their interrelationship. Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102 MS patients and 42 healthy controls. Gray matter networks were computed at the group‐level based on cortical thickness correlations between 78 regions across subjects. MEG functional networks were computed at the subject level based on the phase‐lag index between time‐series of regions in source‐space. In MS patients, we found a more regular network organization for structural covariance networks and for functional networks in the theta band, whereas we found a more random network organization for functional networks in the alpha2 band. Correlation analysis revealed a positive association between covariation in thickness and functional connectivity in especially the theta band in MS patients, and these results could not be explained by simple regional gray matter thickness measurements. This study is a first multimodal graph analysis in a sample of MS patients, and our results suggest that a disruption of gray matter network topology is important to understand alterations in functional connectivity in MS as regional gray matter fails to take into account the inherent connectivity structure of the brain. Hum Brain Mapp 35:5946–5961, 2014. © 2014 Wiley Periodicals, Inc.