Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor ...cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual's unique physiology.
High systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic ...estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation.
Fifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, β-glucuronidase and β-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created zero, low (below median of detected sequences), high and compared to loge estrogens, β-glucuronidase and β-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with α=0.05.
In men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R≥0.50, P≤0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57-0.70, P=0.03-0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal β-glucuronidase (R=0.36, P=0.04). In contrast, fecal β-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R≤-0.47, P≤0.01). Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P≥0.6).
Intestinal microbial richness and functions, including but not limited to β-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions.
Retinol Saturase: More than the Name Suggests Weber, Pamela; Flores, Roberto E.; Kiefer, Marie F. ...
Trends in pharmacological sciences (Regular ed.),
June 2020, 2020-06-00, 20200601, Volume:
41, Issue:
6
Journal Article
Peer reviewed
Retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. Thus far, ...RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS). Although initially described to transform retinol to 13,14-dihydroretinol, a function it was named after, alternative enzymatic reactions may underlie some of these biological effects. We summarize recent findings and identify major obstacles standing in the way of its pharmacological exploitation, how we might overcome these, and discuss the therapeutic potential of modulating the activity of RetSat in alleviating human pathologies.
RetSat generates dihydroretinol and shows at least one more enzymatic activity.RetSat enhances adipocyte differentiation, but is downregulated in white adipose tissue of obese mice and humans.RetSat is involved in hepatic glucose and fatty acid metabolism, and regulates de novo lipogenesis and fatty acid desaturation.RetSat controls sensitivity to peroxide-induced toxicity and cellular ROS production.
•Prediction and analysis of Microcystis occurrences in Hitotsuse Dam, Japan.•Feature Engineering and Feature Selection Algorithms applied to water quality data.•There are five water quality factors ...implicated in Microcystis occurrences.•Basic statistics of water quality over a year are related to Microcystis occurrences.•Presents a suitable method for High-Dimension, Low-Sample-Size, and imbalanced data.
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Machine learning, Deep learning, and water quality data have been used in recent years to predict the outbreak of harmful algae, especially Microcystis, and analyze outbreak causes. However, for various reasons, water quality data are often High-Dimension, Low-Sample- Size (HDLSS), meaning the sample size is lower than the number of dimensions. Moreover, imbalance problems may arise due to bias in the occurrence frequency of Microcystis. These problems make predicting the occurrence of Microcystis and analyzing its causes with machine learning difficult. In this study, a machine learning model that applies Feature Engineering (FE) and Feature Selection (FS) algorithms are used to predict outbreaks of Microcystis and analyze the outbreak factors from imbalanced HDLSS water quality data. The prediction performance was verified with binary classification to determine whether Microcystis would occur in the future by applying three machine learning models to four data patterns. The cause analysis of Microcystis occurrence was performed by visualizing the results of applying FE and FS. For the test data, the predictive performance of FE and FS methods was significantly better than that of the conventional method, with an accuracy of .108 points and an F-value of .691 points higher than the conventional method. A prediction performance increase was observed with a smaller model capacity. Data-driven analysis suggested that total nitrogen, chemical oxygen demand, chlorophyll-a, dissolved oxygen saturation, and water temperature are associated with Microcystis occurrences. The results also indicated that basic statistics of the water quality distribution (especially mean, standard deviation, and skewness) over a year, not the concentrations of water components, are related to the occurrence of Microcystis. These are new findings not found in previous studies and are expected to contribute significantly to future studies of algae. This study provides a method for analyzing water quality data with high-dimensionality and small samples, imbalance problems, or both.
Relative value units (RVUs) are broadly used for billing and physician compensation; however, the accuracy of RVU assignments has not been scientifically evaluated for craniofacial surgery. The ...authors hypothesize that unbalanced RVU allocation creates inappropriate disparities in value among procedures performed by cleft and craniofacial surgeons.
The National Surgical Quality Improvement Program Pediatric database was queried to identify all cleft and craniofacial surgery cases performed by plastic surgeons from 2012 to 2019 based on CPT code. Microsurgical cases and CPT codes with a case count of fewer than 10 were excluded. Efficiency was defined as total RVUs divided by total operative time (ie, RVUs/hour). Mean efficiency per CPT code was ranked and compared by quartile using t tests.
The sample consisted of 69 CPT codes with 50,450 cases. In the top quartile, most CPT codes were craniofacial procedures including frontofacial procedures (23.53%) and craniectomies for craniosynostosis or bony lesions (35.29%) (mean, 15.65 ± 4.22 RVUs/hour). The lowest quartile was composed mainly of CPT codes for cleft procedures including operations for velopharyngeal insufficiency (17.65%), cleft palate repair (23.53%), and cleft septoplasty (5.88%) (mean, 7.39 ± 0.98 RVUs/hour; P < 0.001). It was 2.5 times more efficient for a cleft and craniofacial surgeon to perform a local skin flap (15.18 RVUs/hour) than a secondary palatal lengthening for cleft palate (6.09 RVUs/hour).
The current RVU allocation to cleft and craniofacial procedures creates arbitrary disparities in physician efficiency, with cleft procedures disproportionately negatively affected. RVU assignments should be reevaluated to avoid disincentivizing cleft surgical care.
BACKGROUND:The authors present an outcomes analysis of mandibular distraction osteogenesis versus tongue-lip adhesion in the surgical treatment of Pierre Robin sequence.
METHODS:A retrospective, ...15-year, single-surgeon review was undertaken of all nonsyndromic neonates with Pierre Robin sequence treated with mandibular distraction osteogenesis (2004 to 2009; n = 24) or tongue-lip adhesion (1994 to 2004; n = 15). Outcomes included time of extubation, length of intensive care unit stay, incidence of tracheostomy, and surgical complications. Polysomnography data were collected 1 month and 1 year postoperatively. Sleep study data included changes in oxygen saturation and apnea-hypopnea index.
RESULTS:There were no postprocedure tracheostomies in the mandibular distraction osteogenesis group and four tracheostomies in the tongue-lip adhesion group. The preoperative oxygen saturations were significantly lower in the mandibular distraction osteogenesis group compared with tongue-lip adhesion (76.5 percent versus 82 percent; p < 0.05). Preoperative apnea-hypopnea index was significantly higher in the mandibular distraction osteogenesis group compared with the tongue-lip adhesion group (47 versus 37.6; p < 0.05). Despite these preoperative differences, patients undergoing mandibular distraction osteogenesis demonstrated significantly higher oxygen saturation levels at 1 month (98.3 percent versus 87.5 percent; p < 0.05) and 1 year postoperatively (98.5 percent versus 89.2 percent; p < 0.05) and lower apnea-hypopnea index at 1 month (10.9 versus 21.6; p < 0.05) and 1 year postoperatively (2.5 versus 22.1; p < 0.05) compared with tongue-lip adhesion. Surgical complications were comparable between the two groups.
CONCLUSIONS:In nonsyndromic patients with Pierre Robin sequence, mandibular distraction osteogenesis demonstrates superior outcome measures regarding oxygen saturation, apnea-hypopnea index, and incidence of tracheostomy compared with tongue-lip adhesion.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.
Commercial payer-negotiated rates for cleft lip and palate surgery have not been evaluated on a national scale. The aim of this study was to characterize commercial rates for cleft care, both in ...terms of nationwide variation and in relation to Medicaid rates.
A cross-sectional analysis was performed of 2021 hospital pricing data from Turquoise Health, a data service platform that aggregates hospital price disclosures. The data were queried by CPT code to identify 20 cleft surgical services. Within- and across-hospital ratios were calculated per CPT code to quantify commercial rate variation. Generalized linear models were utilized to assess the relationship between median commercial rate and facility-level variables, and between commercial and Medicaid rates.
There were 80,710 unique commercial rates from 792 hospitals. Within-hospital ratios for commercial rates ranged from 2.0-2.9, while across-hospital ratios ranged from 5.4-13.7. Median commercial rates per facility were higher than Medicaid rates for primary cleft lip and palate repair ($5,492.2 vs. $1,739.0), secondary cleft lip and palate repair ($5,429.1 vs. $1,917.0), and cleft rhinoplasty ($6,001.0 vs. $1,917.0) (p<0.001). Lower commercial rates were associated with hospitals that were smaller (p<0.001), safety-net (p<0.001), and non-profit (p<0.001). Medicaid rate was positively associated with commercial rate (p<0.001).
Commercial rates for cleft surgical care demonstrated marked variation within and across hospitals, and were lower for small, safety-net, and/or non-profit hospitals. Lower Medicaid rates were not associated with higher commercial rates, suggesting that hospitals did not utilize cost-shifting to compensate for budget shortfalls resulting from poor Medicaid reimbursement.
Background
This study characterizes the potential loss of velar length in patients with a wide cleft and rescue of this loss of domain by local flap reconstruction, providing anatomic evidence in ...support of primary lengthening of the soft palate during palatoplasty.
Methods
A retrospective review was conducted of all patients with a cleft palate at least 10mm in width, who underwent primary palatoplasty with a buccal flap prior to 18 months of age over a 2-year period. All patients underwent primary palatoplasty with horizontal transection of the nasal mucosa, which was performed after nasal mucosa repair, but prior to muscular reconstruction. The resulting palatal lengthening was measured and the mucosal defect was reconstructed with a buccal flap.
Results
Of the 22 patients included, 3 (13.6%) had a history of Pierre Robin sequence, and 5 (22.7%) had an associated syndrome. No patients had a Veau I cleft, 7 (31.8%) had a Veau II, 12 (54.5%) had a Veau III, and 3 had (13.6%) a Veau IV cleft. All patients had a right buccal flap during primary palatoplasty. The mean cleft width at the posterior nasal spine was 10.6 ± 2.82mm, and mean lengthening of the velum after horizontal transection of the nasal mucosa closure was 10.5 ± 2.23mm. There were 2 (9.1%) fistulas, 1 (4.5%) wound dehiscence, 1 (4.5%) 30-day readmission, and no bleeding complications.
Conclusions
Patients with a wide cleft palate have a potential loss of 1cm velar length. The buccal flap can rescue the loss of domain in palatal length, and potentially improve palatal excursion.
Infectious myonecrosis virus (IMNV) has impacted the sustainable growth of shrimp aquaculture in Brazil and other shrimp farming nations around the globe. This virus contains a non-segmented dsRNA of ...~8.2 kbp and has been tentatively assigned to the family Totiviridae. In recent years in Brazil (2016 to 2021), unusual mortalities that do not follow the normal course of infection described for IMNV have been observed in several states (Pará, Maranhão, Piaui, Ceará, Rio Grande do Norte, Alagoas, Sergipe and Bahia). Moribund animals are tested PCR positive and histological examination reveals the characteristic lesions caused by IMNV. In this study, we used Next Generation Sequencing to determine the complete genome of a novel IMNV strain (Br-1) from the state of Ceara from the 2018 culture cycle associated with unusually high mortalities. The full-length genome of Br-1 is 8185 bp and shows 97.94% identity to the reference strain. Sequence comparison using the RdRp region and phylogenetic analysis using the full-length genome of Br-1 revealed that this strain is more closely related with IMNV strains from Indonesia rather than strains from Brazil. These findings suggest a potential movement of animals between shrimp farming regions and underscores the importance to enforce stricter testing measures to reduce the risk of spreading lethal pathogens that could compromise the sustainability of shrimp aquaculture worldwide.
•The full-length genome of a novel variant of infectious myonecrosis virus (IMNV) associated with increased mortality in shrimp aquaculture in Brazil was characterized•The IMNV variant appears to be more closely related to strains from Indonesia•These finding suggest potential movement of animals between shrimp farming countries
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