Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking ...the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein diet, but not when mice are fed a HFD with low energy density (high fiber). Furthermore, mice with an activating mutation in NLRP1, and hence increased IL-18, have decreased adiposity and are resistant to diet-induced metabolic dysfunction. Feeding these mice a HFD further increased plasma IL-18 concentrations and strikingly resulted in loss of adipose tissue mass and fatal cachexia, which could be prevented by genetic deletion of IL-18. Thus, NLRP1 is an innate immune sensor that functions in the context of metabolic stress to produce IL-18, preventing obesity and metabolic syndrome.
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•Deletion of NLRP1 in mice leads to obesity and metabolic syndrome•NLRP1 obesity phenotype is related to the energy quotient of the diet•Loss of NLRP1 decreased IL-18 production and lipolysis•NLRP1 activation increased IL-18, prevented obesity, but was fatal on the high-fat diet
Murphy et al. link the NLRP1 inflammasome to IL-18 production and show that mice lacking NLRP1 have defective lipolysis and become obese, as seen with IL-18 deficiency. NLRP1 activation prevents obesity but results in fatal fat loss and cachexia on a high-fat diet, which is rescued by deletion of IL-18.
ENCODE data at the ENCODE portal Sloan, Cricket A; Chan, Esther T; Davidson, Jean M ...
Nucleic acids research,
01/2016, Letnik:
44, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion ...of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments.
The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding best practices for ...use of telemedicine in gastroenterology and hepatology.
This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important, as well as recently published, studies in this field, and it reflects the experiences of the authors who are active gastroenterologists and hepatologists with extensive experience using telemedicine in clinical practice.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults.
To update the 2008 US Preventive Services Task ...Force (USPSTF) recommendation on screening for lipid disorders in adults.
The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.
The USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).
A 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. ...We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE.
We recruited children (1-18 years old, diagnosed per consensus guidelines) from 4 medical centers. Study participants (n = 78) were given a proton pump inhibitor twice daily and underwent a baseline esophagogastroduodenoscopy. Subjects were instructed on dietary exclusion of cow's milk, wheat, egg, and soy. Clinical, endoscopic, and histologic assessments were made after 8 weeks. Responders had single foods reintroduced for 8 weeks, with repeat endoscopy to assess for recurrence of active disease. The primary endpoint was histologic remission (fewer than 15 eosinophils per high-powered field). Secondary endpoints included symptom and endoscopic improvements and identification of foods associated with active histologic disease.
After 8 weeks on 4-food elimination diet, 50 subjects were in histologic remission (64%). The subjects' mean baseline clinical symptoms score was 4.5, which decreased to 2.3 after 8 weeks of 4-food elimination diet (P < .001). The mean endoscopic baseline score was 2.1, which decreased to 1.3 (P < .001). After food reintroduction, the most common food triggers that induced histologic inflammation were cow's milk (85%), egg (35%), wheat (33%), and soy (19%). One food trigger that induced recurrence of esophageal inflammation was identified in 62% of patients and cow's milk-induced EoE was present in 88% of these patients.
In a prospective study of children with EoE, 8 weeks of 4-food elimination diet induced clinical, endoscopic, and histologic remission in more than 60% of children with EoE. Although less restrictive than 6-food elimination diet, 4-food elimination diet was nearly as effective, and can be recommended as a treatment for children with EoE.
Activation of the intrarenal renin-angiotensin system (RAS) can elicit hypertension independently from the systemic RAS. However, the precise mechanisms by which intrarenal Ang II increases blood ...pressure have never been identified. To this end, we studied the responses of mice specifically lacking kidney angiotensin-converting enzyme (ACE) to experimental hypertension. Here, we show that the absence of kidney ACE substantially blunts the hypertension induced by Ang II infusion (a model of high serum Ang II) or by nitric oxide synthesis inhibition (a model of low serum Ang II). Moreover, the renal responses to high serum Ang II observed in wild-type mice, including intrarenal Ang II accumulation, sodium and water retention, and activation of ion transporters in the loop of Henle (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases SPAK and OSR1, were effectively prevented in mice that lack kidney ACE. These findings demonstrate that ACE metabolism plays a fundamental role in the responses of the kidney to hypertensive stimuli. In particular, renal ACE activity is required to increase local Ang II, to stimulate sodium transport in loop of Henle and the distal nephron, and to induce hypertension.
Summary
Microalgae as a biofuel source are of great interest. Bacterial phycosphere inhabitants of algal cultures are hypothesized to contribute to productivity. In this study, the bacterial ...composition of the Chlorella sorokiniana phycosphere was determined over several production cycles in different growing seasons by 16S rRNA gene sequencing and identification. The diversity of the phycosphere increased with time during each individual reactor run, based on Faith’s phylogenetic diversity metric versus days post‐inoculation (R = 0.66, P < 0.001). During summer months, Vampirovibrio chlorellavorus, an obligate predatory bacterium, was prevalent. Bacterial sequences assigned to the Rhizobiales, Betaproteobacteriales and Chitinophagales were positively associated with algal biomass productivity. Applications of the general biocide, benzalkonium chloride, to a subset of experiments intended to abate V. chlorellavorus appeared to temporarily suppress phycosphere bacterial growth, however, there was no relationship between those bacterial taxa suppressed by benzalkonium chloride and their association with algal productivity, based on multinomial model correlations. Algal health was approximated using a model‐based metric, or the ‘Health Index’ that indicated a robust, positive relationship between C. sorokiniana fitness and presence of members belonging to the Burholderiaceae and Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium clade. Bacterial community composition was linked to the efficiency of microalgal biomass production and algal health.
Microalgae can be efficiently cultivated to produce biomass suitable for conversion to liquid biofuels. Long term experiments conducted over multiple growing seasons in the arid Southwest region of the United States revealed significant associations between algal productivity and the bacterial members of the culture phycospheres. These species offer targets for improving algal biomass yields in mass cultivation.
We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett’s esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel ...using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers.
Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis.
The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy.
A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT 02560623.)
Templating for Total Hip Arthroplasty in the Modern Age Vigdorchik, Jonathan M; Sharma, Abhinav K; Jerabek, Seth A ...
Journal of the American Academy of Orthopaedic Surgeons,
2021-Mar-01, Letnik:
29, Številka:
5
Journal Article
Recenzirano
Preoperative templating provides several benefits to the patient, surgeon, and hospital. Appropriate implant selection and sizing optimizes surgical workflow and leads to efficient care-delivery ...systems. Accurate templating establishes intraoperative targets for component position and reduces complications such as leg length inequality, impingement, wear, dislocation, and fracture, all of which lead to decreased patient satisfaction. Recent technological advances in preoperative imaging include a better understanding of patient-specific pelvic motion allowing the surgeon to preoperatively address the risk of lumbar pathology with adjustments in component placement and bearing choice. The introduction of two-dimensional to three-dimensional (3D) radiographs, biplanar low-dose radiographs, and computed tomography scans with 3D reconstructions have all allowed for a more comprehensive preoperative planning in 3D. This article will review the fundamentals of templating before total hip arthroplasty with an emphasis on how to incorporate and implement patient-specific pelvic motion and 3D templating into practice.
Empirical evidence suggests that synesthesia is associated with enhanced sensory processing. A separate body of empirical literature suggests that synesthesia is linked to a specific profile of ...enhanced episodic and working memory performance. However, whether sensory (iconic) memory performance is also affected by synesthesia remains unknown. Therefore, we tested 22 grapheme-color synesthetes and compared their performance in a partial-report paradigm with 22 individually matched non-synesthete controls. Participants were briefly presented with a circular-letter array and required to report the identity of the letter at a probed target location after various delays. Furthermore, they were required to indicate the subjective clarity of the target letter after every trial. The results suggest that sensory memory performance is enhanced in synesthesia, but only when subjective clarity of the target letter is high. Additional exploratory analyses revealed that synesthetic consistency, which is widely used to confirm the genuineness of synesthesia, correlated significantly with performance in the partial report paradigm. We conclude that synesthesia does not generally enhance sensory memory performance, but that synesthetic experiences may enhance sensory memory performance when perceptual awareness of the target is high. Furthermore, the stability of synesthetic associations may be linked to sensory memory performance.
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