Posterior Decompression and Fusion: Whole-Spine Functional and Clinical Outcomes

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group

All-cause and liver-related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Background: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. Methods: We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. Results: Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment. Conclusions: People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality

Parenting Styles: A Closer Look at a Well-Known Concept

Although parenting styles constitute a well-known concept in parenting research, two issues have largely been overlooked in existing studies. In particular, the psychological control dimension has rarely been explicitly modelled and there is limited insight into joint parenting styles that simultaneously characterize maternal and paternal practices and their impact on child development. Using data from a sample of 600 Flemish families raising an 8-to-10 year old child, we identified naturally occurring joint parenting styles. A cluster analysis based on two parenting dimensions (parental support and behavioral control) revealed four congruent parenting styles: an authoritative, positive authoritative, authoritarian and uninvolved parenting style. A subsequent cluster analysis comprising three parenting dimensions (parental support, behavioral and psychological control) yielded similar cluster profiles for the congruent (positive) authoritative and authoritarian parenting styles, while the fourth parenting style was relabeled as a congruent intrusive parenting style. ANOVAs demonstrated that having (positive) authoritative parents associated with the most favorable outcomes, while having authoritarian parents coincided with the least favorable outcomes. Although less pronounced than for the authoritarian style, having intrusive parents also associated with poorer child outcomes. Results demonstrated that accounting for parental psychological control did not yield additional parenting styles, but enhanced our understanding of the pattern among the three parenting dimensions within each parenting style and their association with child outcomes. More similarities than dissimilarities in the parenting of both parents emerged, although adding psychological control slightly enlarged the differences between the scores of mothers and fathers

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

DOP29 Elevation of a novel blood-based gene signature in a severe Crohn’s disease (CD) subtype preceding surgery defines and predicts a post-surgical decrease in pro-inflammatory pathway activation

Abstract Background CD is defined by transmural inflammation leading to inflammatory, stricturing and/or penetrating phenotypes. Identifying underlying molecular pathways and distinct disease subsets is critical for improved prognostics, therapeutics and biomarker discovery. Methods CD3+ T cells were purified from paired blood and mucosal tissue from 101 CD and 17 non-IBD subjects requiring surgery. Longitudinal samples (n = 30) were collected 4–13 mo. post-surgery. Expression profiles were generated by RNAseq, T-cell subset deconvolution by xCell and transcriptome-wide associations (TWAS) using TWAS-hub. Results Unsupervised clustering of peripheral T-cell gene expression at surgery revealed 2 CD profiles: Expression from cluster1, labelled CD-PBT (63%), clustered tightly with the non-IBD group. In cluster2, expression shifted from a peripheral toward a mucosal profile, labelled CD-PBmu(cosal) (37%). CD-PBmu was defined by differentially expressed genes (DEG) (1944 DEG, p &amp;lt; 0.001) regulating cell migration and adhesion pathways and a distinct T-cell subset composition associated with stricturing disease (p = 0.03), increased resected bowel length (p = 0.036) and post-op recurrence (p = 0.01). There were no significant differences in disease location/behaviour. Independent validation (5 public datasets) confirmed the CD-PBmu signature in data from whole blood (CD patients failing anti-TNF therapy, n = 204) and the mucosal-like expression profile in data from ileal tissue (paediatric CD patients, studies n = 751). A defining feature of CD-PBmu, validated in a separate CD cohort (n = 19), was decreased pro-inflammatory cytokine/chemokine and adhesion molecule expression following surgery (900 DEG, p &amp;lt; 0.001). No post-surgery change in expression was detected in CD-PBT. A 44-gene classifier was identified to enable clinical application. The classifier accurately detected the CD-PBmu patient subtype, correlated with the altered composition of peripheral T-cell subsets and overlapped with IBD associated TWAS signals (&amp;gt;60%). Recently, another group posed a blood-based 17 gene panel as predictive for aggressive IBD. These genes were not predictive for either the CD-PBmu or CD-PBT subtype (&amp;lt;50% DEG). Conclusion Severe CD can be stratified into 2 subtypes based on peripheral T-cell gene expression. Circulating T cells from CD-PBmu exhibit a mucosal-like gene signature, altered T-cell subset composition, clinical features of severity and decreased pro-inflammatory gene expression post-surgery. These findings hold potential to identify targets for CD subtype-specific therapeutic development. The 44-gene classifier overlapped with multiple paediatric CD datasets, suggesting the potential application of these findings for treatment stratification early in the disease process. </jats:sec

Fusion-power demonstration. [Next step beyond MFTF-B]

As a satellite to the MARS (Mirror Advanced Reactor Study) a smaller, near-term device has been scoped, called the FPD (Fusion Power Demonstration). Envisioned as the next logical step toward a power reactor, it would advance the mirror fusion program beyond MFTF-B and provide an intermediate step toward commercial fusion power. Breakeven net electric power capability would be the goal such that no net utility power would be required to sustain the operation. A phased implementation is envisioned, with a deuterium checkout first to verify the plasma systems before significant neutron activation has occurred. Major tritium-related facilities would be installed with the second phase to produce sufficient fusion power to supply the recirculating power to maintain the neutral beams, ECRH, magnets and other auxiliary equipment