Citations

The ability to regulate behavior in service of long-term goals is a widely studied psychological construct known as self-regulation. This wide interest is in part due to the putative relations between self-regulation and a range of real-world behaviors. Self-regulation is generally viewed as a trait, and individual differences are quantified using a diverse set of measures, including self-report surveys and behavioral tasks. Accurate characterization of individual differences requires measurement reliability, a property frequently characterized in self-report surveys, but rarely assessed in behavioral tasks. We remedy this gap by ( i ) providing a comprehensive literature review on an extensive set of self-regulation measures and ( ii ) empirically evaluating test–retest reliability of this battery in a new sample. We find that dependent variables (DVs) from self-report surveys of self-regulation have high test–retest reliability, while DVs derived from behavioral tasks do not. This holds both in the literature and in our sample, although the test–retest reliability estimates in the literature are highly variable. We confirm that this is due to differences in between-subject variability. We also compare different types of task DVs (e.g., model parameters vs. raw response times) in their suitability as individual difference DVs, finding that certain model parameters are as stable as raw DVs. Our results provide greater psychometric footing for the study of self-regulation and provide guidance for future studies of individual differences in this domain.

Background. Active antibody-mediated rejection (AMR) that occurs during the amnestic response within the first month posttransplant is a rare but devastating cause of early allograft loss after kidney transplant. Prior reports of eculizumab treatment for AMR have been in heterogeneous patient groups needing salvage therapy or presenting at varied time points. We investigated the role of eculizumab as primary therapy for active AMR early posttransplant. Methods. We performed a retrospective observational study of a consecutive cohort of solitary kidney transplant recipients who were transplanted between January 1, 2014, and January 31, 2018, and had AMR within the first 30 days posttransplant and treated with eculizumab ± plasmapheresis. Results. Fifteen patients had early active AMR at a median (interquartile range [IQR]) of 10 (7–11) days posttransplant and were treated with eculizumab ± plasmapheresis. Thirteen cases were biopsy proven, and 2 cases were presumed on the basis of donor-specific antibody trends and allograft function. Within 1 week of treatment, the median estimated glomerular filtration rate increased from 21 to 34 mL/min (P = 0.001); and persistent active AMR was only found in 16.7% (2/12) of biopsied patients within 4–6 months. No graft losses occurred, and at last follow-up (median [IQR] of 13 [12–19] mo), the median IQR estimated glomerular filtration rate increased to 52 (46–60) mL/min. Conclusions. Prompt eculizumab treatment as primary therapy is safe and effective for early active AMR after kidney transplant or abrupt increases in donor-specific antibodies when biopsy cannot be performed for diagnosis confirmation.

Background: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. Objective: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. Methods: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. Results: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission ( P = .98), mechanical ventilation ( P = .92), or 30-day mortality ( P = .11). Conclusions: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.

Abstract Background and Aims Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn’s disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. Methods This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. Results Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7–2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. Conclusions Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.

Little data is available regarding the energy and nutritional status of female collegiate team sport athletes. Twenty female NCAA Division II lacrosse athletes (mean ± SD: 20.4 ± 1.8 years; 68.8 ± 8.9 kg; 168.4 ± 6.6 cm; 27.9 ± 3% body fat) recorded dietary intake and wore a physical activity monitor over four consecutive days at five different time points (20 days total) during one academic year. Body composition, bone health, and resting metabolic rate were assessed in conjunction with wearing the monitor during off-season, pre-season, and season-play. Body fat percentage decreased slightly during the course of this study (p = 0.037). Total daily energy expenditure (TDEE) (p < 0.001) and activity energy expenditure (AEE) (p = 0.001) energy were found to change significantly over the course of the year, with pre-season training resulting in the highest energy expenditures (TDEE: 2789 ± 391 kcal/day; AEE: 1001 ± 267 kcal/day). Caloric (2124 ± 448 kcal/day), carbohydrate (3.6 ± 1.1 g/kg), and protein (1.2 ± 0.3 g/kg) intake did not change over the course of the year (p > 0.05). Athletes self-reported a moderate negative energy balance (366–719 kcal/day) and low energy availability (22.9–30.4 kcal/kg FFM) at each measurement period throughout the study. Reported caloric and macronutrient intake was low given the recorded energy expenditure and macronutrient intake recommendations for athletes. Athletic support staff should provide athletes with appropriate fueling strategies, particularly during pre-season training, to adequately meet energy demands.

AbstractPrimary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full‐length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell‐rich primary bone tumors. In this report, we present a case of a 16‐year‐old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X‐USP6 promoter swap fusion. This result was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin‐specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate‐specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.

How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang et al. engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression. Science , this issue p. eaav2606

AbstractBackgroundWe reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients.MethodsA total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow‐up of 7 ± 4 years. Eighty‐nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy.ResultsThe 10‐year disease‐free and disease‐specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59‐2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45‐1.91; P = 0.85) or disease‐specific survival (HR, 0.96; 95% CI, 0.46‐2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20‐1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64‐4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88‐14.38; P < 0.001).ConclusionsIn this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en‐bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.

DDX3X (Xp11.4) encodes a DEAD‐box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X‐linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with DDX3X variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and/or spasticity. The majority of DDX3X variants described are de novo mutations in females with ID. In contrast, most male DDX3X variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant. It has been suggested, therefore, that DDX3X exerts its effects through haploinsufficiency in females, and that affected males carry hypomorphic alleles that retain partial function. Given the lack of male de novo DDX3X variants, loss‐of‐function variants in this gene are suspected to be male lethal. Through whole‐exome sequencing, we identified three unrelated males with hemizygous missense DDX3X variants and ID. All three variants were confirmed by Sanger sequencing, with two established as de novo. In silico analyses were supportive of pathogenicity. We report the male phenotypes and compare them to phenotypes observed in previously reported male and female patients. In conclusion, we propose that de novo DDX3X variants are not necessarily male lethal and should be considered as a cause of syndromic ID in both males and females.