Purpose
High complication rates following colorectal surgery render many patients unable to fully regain functional capacity, thus seriously compromising quality of life. The aim of this study was to ...assess whether a 4-week trimodal prehabilitation program (exercise, nutritional supplementation, and counseling on relaxation techniques), implemented during the preoperative period, is sufficient to modify exercise behaviors and improve functional capacity of elderly patients scheduled for colorectal cancer surgery.
Methods
Patients were assigned to either a prehabilitation (PREHAB;
n
= 57) or matched time control group (CTRL;
n
= 59). Over the 4-week period prior to surgery, patients in PREHAB participated in a trimodal prehabilitation program. Patients in CTRL received the same program but only postoperatively. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to measure physical activity levels, while the 6-min walk test (6MWT) was used for assessment of functional walking capacity. Measurements were collected at baseline and at the time of surgery.
Results
Over the preoperative period, patients in PREHAB significantly increased the amount of moderate- and vigorous-intensity physical activities that they performed. PREHAB patients also demonstrated a greater improvement in 6MWT compared to CTRL. At the time of surgery, a greater proportion of patients in PREHAB met current physical activity guidelines, as compared to CTRL.
Conclusions
These findings highlight the positive effects of a trimodal prehabilitation program on patients’ physical activity levels and functional walking capacity and demonstrate that modifying exercise behaviors and improving physical function within the 4-week preoperative period are an achievable goal.
Lighting is an important component of consistent, high-quality dermatologic photography. There are different types of lighting solutions available.
To evaluate currently available lighting equipment ...and methods suitable for procedural dermatology.
Overhead lighting, built-in camera flashes, external flash units, studio strobes, and light-emitting diode (LED) light panels were evaluated with regard to their utility for dermatologic surgeons. A set of ideal lighting characteristics was used to examine the capabilities and limitations of each type of lighting solution. Recommendations regarding lighting solutions and optimal usage configurations were made in terms of the context of the clinical environment and the purpose of the image.
Overhead lighting may be a convenient option for general documentation. An on-camera lighting solution using a built-in camera flash or a camera-mounted external flash unit provides portability and consistent lighting with minimal training. An off-camera lighting solution with studio strobes, external flash units, or LED light panels provides versatility and even lighting with minimal shadows and glare.
The selection of an optimal lighting solution is contingent on practical considerations and the purpose of the image.
Accurate measurement of the amount of specific protein a cell produces is important for investigating basic molecular processes. We have developed a technique that allows for quantitation of protein ...levels in single cells in vivo. This protein quantitation ratioing (PQR) technique uses a genetic tag that produces a stoichiometric ratio of a fluorescent protein reporter and the protein of interest during protein translation. The fluorescence intensity is proportional to the number of molecules produced of the protein of interest and is used to determine the relative amount of protein within the cell. We use PQR to quantify protein expression of different genes using quantitative imaging, electrophysiology, and phenotype. We use genome editing to insert Protein Quantitation Reporters into endogenous genomic loci in three different genomes for quantitation of endogenous protein levels. The PQR technique will allow for a wide range of quantitative experiments examining gene-to-phenotype relationships with greater accuracy.
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•Protein levels can be quantified using a fluorescent reporter•Relative protein levels can be quantified in single living cells•Genome editing allows for quantification of endogenous protein levels•The PQR technique has broad possible applications
Lo et al. describe a technique called protein quantitation ratioing that allows for quantification of protein amounts in single cells in the living animal. The technique uses the fluorescence intensity of a reporter as a readout for the concentration of a protein within a cell.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fragile X syndrome is caused by the loss of Fragile X mental retardation protein (FMRP), an RNA-binding protein that suppresses protein translation. We found that FMRP binds to Down syndrome cell ...adhesion molecule (Dscam) RNA, a molecule that is involved in neural development and has been implicated in Down syndrome. Elevated Dscam protein levels in FMRP null Drosophila and in flies with three copies of the Dscam gene both produced specific and similar synaptic targeting errors in a hard-wired neural circuit, which impaired the flies' sensory perception. Reducing Dscam levels in FMRP null flies reduced synaptic targeting errors and rescued behavioral responses. Our results indicate that excess Dscam protein may be a common molecular mechanism underlying altered neural wiring in intellectual disabilities such as Fragile X and Down syndromes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Summary
Identifying genomic features responsible for genome-wide association study (GWAS) signals has proven to be a difficult challenge; many researchers have turned to colocalization ...analysis of GWAS signals with expression quantitative trait loci (eQTL) and splicing quantitative trait loci (sQTL) to connect GWAS signals to candidate causal genes. The ColocQuiaL pipeline provides a framework to perform these colocalization analyses at scale across the genome and returns summary files and locus visualization plots to allow for detailed review of the results. As an example, we used ColocQuiaL to perform colocalization between a recent type 2 diabetes GWAS and Genotype-Tissue Expression (GTEx) v8 single-tissue eQTL and sQTL data.
Availability and implementation
ColocQuiaL is primarily written in R and is freely available on GitHub: https://github.com/bvoightlab/ColocQuiaL.
CenteringPregnancy emphasizes nutrition, learning, and peer support through a group meeting format in contrast to the standard of prenatal care that maximizes a pregnant patient's time with their ...provider. It was hypothesized that the program may yield a reduced risk of pregnancy-induced hypertension. In this observational study, authors examined the impacts of the CenteringPregnancy program versus those of standard of prenatal care on pregnancy-induced hypertension.
In 2021, birth certificate data were linked to hospital discharge records of women who delivered in obstetric clinics in the Midlands of South Carolina between 2015 and 2019. Logistic regression models were used to estimate the association between CenteringPregnancy participation (n=547) and any pregnancy-induced hypertension and specific pregnancy-induced hypertension diagnoses (gestational hypertension/unspecified hypertension, mild pre-eclampsia, and severe pre-eclampsia/eclampsia). Propensity score techniques (e.g., inverse probability of treatment weighting) were used to adjust for self-selection into the program versus into standard of prenatal care.
CenteringPregnancy participants had higher odds of developing any pregnancy-induced hypertension under all specifications (OR=1.48, 95% CI=1.15, 1.92) and specifically gestational hypertension/unspecified hypertension (OR=1.76, 95% CI=1.28, 2.42) than those in standard of prenatal care. However, CenteringPregnancy participants did not experience significantly higher odds of mild pre-eclampsia (OR=1.06, 95% CI=0.65, 1.78) and severe pre-eclampsia/eclampsia (OR=1.21, 95% CI=0.78, 1.89) compared with standard of prenatal care participants.
Participation in CenteringPregnancy was associated with higher odds of pregnancy-induced hypertension, particularly gestational hypertension, than participation in standard of prenatal care. Additional research is warranted to definitely rule out selection bias and identify contributing factor(s) that increased pregnancy-induced hypertension despite efforts to improve pregnancy-related health outcomes among CenteringPregnancy participants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
There is significant interest and controversy surrounding the effect of restrictive fluid management on outcomes in major gastrointestinal surgery. This has been most studied in colorectal ...surgery, although the literature relating to pancreaticoduodenectomy (PD) patients is growing. The aim of this paper was to generate a comprehensive review of the available evidence for restrictive perioperative fluid management strategies and outcomes in PD.
Methods
MEDLINE/PubMed, Embase, and the Cochrane Library were searched from inception to April 2017. A review protocol was utilized and registered with PROSPERO. Primary citations that evaluated perioperative fluid management in PD, including those as part of a clinical pathway, were considered. The primary outcome was postoperative pancreatic fistula (POPF). Secondary outcomes included delayed gastric emptying (DGE), complication rate, length of stay (LOS), mortality, and readmission.
Results
A total of six studies involving 846 patients were included (2009–2015), of which four were RCTs. Pooled analysis of RCTs and high-quality observational studies found no effect of restrictive intraoperative fluid management on POPF, DGE, complication rate, LOS, mortality, and readmission. Only one study assessed postoperative fluid management exclusively and found prolonged LOS in patients in the restricted fluid group.
Conclusion
Based on results of RCTs and high-quality observational studies, intraoperative fluid restriction in PD has not been shown to significantly affect postoperative outcomes. There are too few studies assessing postoperative fluid management to draw conclusions at this time.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Allelic expression from each parent-of-origin is important as a backup and to ensure that enough protein products of a gene are produced. Thus far, it is not known how each cell throughout a tissue ...differs in parental allele expression at the level of protein synthesis. Here, we measure the expression of the Ribosomal protein L13a (Rpl13a) from both parental alleles simultaneously in single cells in the living animal. We use genome-edited Drosophila that have a quantitative reporter of protein synthesis inserted into the endogenous Rpl13a locus. We find that individual cells can have large (>10-fold) differences in protein expression between the two parental alleles. Cells can produce protein from only one allele oftentimes, and time-lapse imaging of protein production from each parental allele in each cell showed that the imbalance in expression from one parental allele over the other can invert over time. We also identify the histone methyltransferase EHMT to be involved in the protein synthesis dynamics within cells.
•We quantified protein expression of both parental alleles simultaneously over time in single cells in the awake animal.•Cells can have a large difference in protein expression for one allele over the other, and this can invert over time.•We demonstrate the highly variable nature of heterozygous and homozygous definitions across single cells, and over time.•The histone methyltransferase EHMT regulates protein synthesis dynamics within cells and between parental alleles.•.This approach can be used to examine epigenetic regulation of allelic expression inherited from progenitor cells
Quantifying parental allele-specific protein expression over time in single cells in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.
We conducted an association study of body mass index (BMI) and differential ...methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 SREBF1), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination.
We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Total joint arthroplasty (TJA) with multi-layer, watertight closure (MLWC) using knotless barbed suture and 2-octyl cyanoacrylate plus polymer mesh tape was compared with conventional closure (CC) ...using Vicryl™ sutures and staples.
Electronic medical records of patients undergoing TJA (1574: total knee arthroplasty; 580: total hip arthroplasty; 13: unknown) from a single surgeon at a US hospital (CC 2011 to 2013; MLWC 2015 to 2020) were reviewed. Outcomes were length of stay (LOS), discharge to skilled nursing facility (SNF), 90-day surgical site infection (SSI) and 90-day readmission. Logistic regression controlled for baseline characteristics. Adjusted interrupted time series (ITS) analyses accounted for decreasing trends in LOS and SNF discharge over time.
Among 2167 TJA cases (mean standard deviation age 66.0 9.7 years, 53.3% female), 906 received CC and 1261 received MLWC. Bivariate analysis showed no statistically significant differences in 90-day SSI rates; however, MLWC patients had 60% lower 90-day readmission rates (1.5 vs 3.8%, p < 0.05), 44% lower LOS (1.4 vs 2.5 days, p < 0.05) and 40% lower discharge rates to a skilled care facility (8.5 vs 14.1%, p < 0.05). Multivariable analyses showed CC patients were 2.45-times more likely to be readmitted within 90 days, 1.88-times more likely to be discharged to SNF and had 1.67-times longer LOS compared with MLWC. ITS analyses showed a sharp decline in LOS (0.9 days) and discharge to SNF (5.6% incidence) after implementation of MLWC, followed by no further changes for the remainder of the study period.
MLWC was associated with ≥40% reduction in 90-day readmission, LOS and SNF discharge compared with TJA CC. LOS and discharge rate to SNF declined sharply after the implementation of MLWC.
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