Background
Previous work from our group demonstrated improved memory function in bariatric surgery patients at 12 weeks postoperatively relative to controls. However, no study has examined ...longer-term changes in cognitive functioning following bariatric surgery.
Methods
A total of 137 individuals (95 bariatric surgery patients and 42 obese controls) were followed prospectively to determine whether postsurgery cognitive improvements persist. Potential mechanisms of change were also examined. Bariatric surgery participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 12-month follow-up; obese controls completed measures at equivalent time points.
Results
Bariatric surgery patients exhibited cognitive deficits relative to well-established standardized normative data prior to surgery, and obese controls demonstrated similar deficits. Analyses of longitudinal change indicated an interactive effect on memory indices, with bariatric surgery patients demonstrating better performance postoperatively than obese controls.
Conclusions
While memory performance was improved 12 months postbariatric surgery, the mechanisms underlying these improvements were unclear and did not appear attributable to obvious postsurgical changes, such as reductions in body mass index or comorbid medical conditions. Future studies employing neuroimaging, metabolic biomarkers, and more precise physiological measurements are needed to determine the mechanisms underlying memory improvements following bariatric surgery.
Primary myelofibrosis (PMF) is a BCR-ABL1 negative myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells. This leads to reactive bone marrow fibrosis, ultimately ...resulting in progressive marrow failure, hepatosplenomegaly, and extramedullary hematopoiesis. PMF is considered the most aggressive of the BCR-ABL1 negative myeloproliferative neoplasms with the least favorable prognosis. Constitutional symptoms are common, which can impact an individual's quality of life and leukemic transformation remains an important cause of death in PMF patients. The development of the Janus kinase 2 (JAK2) inhibitors have provided a good option for management of PMF-related symptoms. Unfortunately, these agents have not been shown to improve overall survival or significantly alter the course of disease. Allogenic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment option in PMF. However, allo-HSCT is associated with significant treatment-related morbidity and mortality and has historically been reserved for younger, high-risk patients. This review examines patient, disease, and transplant-specific factors which may impact transplant-related outcomes in PMF. Through the vast improvements in donor selection, conditioning regimens, and post-transplant care, allo-HSCT may provide a safe and effective curative option for a broader range of PMF patients in the future.
Tradescantia fluminensis Vell. is an invasive species in Australia, New Zealand and South Africa. To assist biocontrol initiatives and management of the species we examine genetic variation in these ...countries and compare this to samples collected from its natural range in Brazil. Tradescantia fluminensis comprises two genetic groupings in New Zealand, both of which are shared with Australia and South Africa. One of these genotypes is relatively common in New Zealand and this is also shared with a Brazilian population. Populations of T. fluminensis in Australia and South Africa are genetically more variable than in New Zealand. Two other entities, T. mundula Kunth (syn. T. albiflora hort.) and T. umbraculifera Hand-Mazz. (syn. T. aff. fluminensis "Big"), new names for naturalised species in New Zealand, also comprise distinct genetic groups. These genetic data emphasise the importance of correct taxonomic identification of weed species being considered for biological control programmes. Tradescantia mundula and T. umbraculifera share a similar genome size and chromosome numbers (2n = 66, 68, 70 and 2C = 14.9 picograms), whereas T. fluminensis had lower values (2n = 56, 58; 2C = 11.7 picograms). Self-pollinations of T. fluminensis and T. umbraculifera failed to produce seed, confirming that these two taxa are self-incompatible. Tradescantia mundula is self-compatible as the majority (93%) of self-pollinations produced fruit. Tradescantia umbraculifera produced a low number of fruit and seeds per fruit when pollinated by T. mundula, but no fruit or seeds were formed when it was pollinated by T. fluminensis. Tradescantia fluminensis pollinated with T. mundula or T. umbraculifera failed to produce fruit or seeds. Self-incompatibility and failure to set seed when cross-pollinated with other species suggests the invasive T. fluminensis does not pose a threat of seedling establishment in indigenous ecosystems and vegetative spread remains the main method of reproduction and invasion.
After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end ...to end, and hundreds of unresolved gaps persist
. Here we present a human genome assembly that surpasses the continuity of GRCh38
, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome
, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.
We have developed a computational method based on polyploid phasing of long sequence reads to resolve collapsed regions of segmental duplications within genome assemblies. Segmental Duplication ...Assembler (SDA; https://github.com/mvollger/SDA ) constructs graphs in which paralogous sequence variants define the nodes and long-read sequences provide attraction and repulsion edges, enabling the partition and assembly of long reads corresponding to distinct paralogs. We apply it to single-molecule, real-time sequence data from three human genomes and recover 33-79 megabase pairs (Mb) of duplications in which approximately half of the loci are diverged (<99.8%) compared to the reference genome. We show that the corresponding sequence is highly accurate (>99.9%) and that the diverged sequence corresponds to copy-number-variable paralogs that are absent from the human reference genome. Our method can be applied to other complex genomes to resolve the last gene-rich gaps, improve duplicate gene annotation, and better understand copy-number-variant genetic diversity at the base-pair level.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains ...unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.
To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.
A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.
A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (
= 0.05), patients on Ursodiol (
< 0.001), and patients on dual therapy (
= 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (
< 0.001) or patients on Ursodiol and CFTR modulators (
= 0.01).
CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.
Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a ...possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population.
Fifty (29 ± 7 yr) men (n = 19) and women (n = 31) classified as overweight (26.4 ± 1.8 kg/m2) participated in this observational study. Blood pressure and blood metabolites were measured after an overnight fast. Lactate was also measured before and after a three-day eucaloric high-fat (70 %) diet. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Visceral adipose tissue mass was determined via dual X-ray absorptiometry.
Triglycerides (r = 0.55, p=<0.0001), HOMA-IR (r = 0.53, p=<0.0001), and systolic and diastolic (both, r = 0.36, p = 0.01) blood pressures associated with fasting plasma lactate. No differences in visceral adipose tissue existed between the sexes (p = 0.41); however, the relationship between visceral adipose tissue and lactate existed only in females (r = 0.59, p = 0.02) but not in males (p = 0.53). Fasting lactate and HOMA-IR increased in males (p = 0.01 and p = 0.02, respectively), but not females, following a three-day high-fat diet.
Indices of the metabolic syndrome associated with fasting plasma lactates in young relatively healthy individuals. Fasting lactate also increased in a sex-specific manner after a three-day high fat diet. Thus, lactate could become a clinical marker for metabolic disease risk.
•Individuals with metabolic disease have elevated fasting plasma lactate.•In healthy subjects, factors of the metabolic syndrome associated with lactate.•Fasting lactate is stable over three separate visits but increased after a three-day high-fat diet.•Fasting lactate may be used as an early biomarker to identify individuals at risk for metabolic disease.
Sulfur is an essential nutrient that contributes to cellular redox homeostasis, transcriptional regulation, and translation initiation when incorporated into different biomolecules. Transport and ...reduction of extracellular sulfate followed by cysteine biosynthesis is a major pathway of bacterial sulfur assimilation. For the opportunistic pathogen
, function of the cysteine biosynthesis pathway is required for extracellular phospholipase activity and flagellum-mediated surface motility, but little else is known about the influence of sulfur assimilation on the physiology of this organism. In this work, it was determined that an
cysteine auxotroph fails to differentiate into hyperflagellated and elongated swarmer cells and that cysteine, but not other organic sulfur molecules, restores swarming motility to these bacteria. The
cysteine auxotroph further exhibits reduced transcription of phospholipase, hemolysin, and flagellin genes, each of which is subject to transcriptional control by the flagellar regulatory system. Based on these data and the central role of cysteine in sulfur assimilation, it was reasoned that environmental sulfur availability may contribute to the regulation of these functions in
Indeed, bacteria that are starved for sulfate exhibit substantially reduced transcription of the genes for hemolysin, phospholipase, and the FlhD flagellar master regulator. A global transcriptomic analysis further defined a large set of
genes that are responsive to extracellular sulfate availability, including genes that encode membrane transport, nutrient utilization, and metabolism functions. Finally, sulfate availability was demonstrated to alter
cytolytic activity, suggesting that sulfate assimilation may impact the virulence of this organism.
is a versatile bacterial species that inhabits diverse environmental niches and is capable of pathogenic interactions with host organisms ranging from insects to humans. This report demonstrates for the first time the extensive impacts that environmental sulfate availability and cysteine biosynthesis have on the transcriptome of
The finding that greater than 1,000
genes are differentially expressed depending on sulfate availability suggests that sulfur abundance is a crucial factor that controls the physiology of this organism. Furthermore, the high relative expression levels for the putative virulence factors flagella, phospholipase, and hemolysin in the presence of sulfate suggests that a sulfur-rich host environment could contribute to the transcription of these genes during infection.
Esophageal varices are a result of progressive liver disease and portal hypertension. Treatment can be performed with band ligation versus non-selective beta blockers depending on the size of ...varices, ability to tolerate medications and history of variceal bleeding. Band ligation is an effective intervention with rare but serious complications including bleeding, ulcers and rarely obstruction. Few cases of esophageal obstruction and necrosis caused by banding have been reported, each with varied management from conservative treatment to band removal.
An 89 years old woman with a past medical history of nonalcoholic steatohepatitis cirrhosis presented to the hospital with an inability to swallow one day after screening esophagogastroduodenoscopy where band ligation of esophageal varices was performed for primary prophylaxis. The patient was not able to tolerate her oral secretions. Initial blood work revealed a Model of End Organ Liver Disease score of 7. She was treated with sublingual nitroglycerin for esophageal spasm, a known complication after esophageal banding. When she failed to improve, esophagogastroduodenoscopy was performed and revealed the mucosa surrounding the banded varix was necrosed and blocking the lumen of the esophagus. The band was purposefully dislodged, revealing distal ulceration and stricturing. Within 72 h after band removal, she was tolerating an oral diet. Endoscopy performed 2 wk later revealed an intrinsic stenosis, measuring 8 mm in diameter by 1 cm in length, which was dilated.
Esophageal obstruction is a complication of variceal banding that should be considered in patients with inability to tolerate oral diet after banding.
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