Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme ...complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599–627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 Å resolution. The Swr1-Z domain forms a 310 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the αC helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.
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•We determined the structure of the Swr1-Z domain-H2A.Z-H2B complex•The conserved Swr1-Z LxxLF motif recognizes the αC helix of H2A.Z•The Swr1-Z domain is a histone chaperone important for SWR1 function•Human p400 and SRCAP include domains similar to Swr1-Z
The conserved SWR1 complex catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. Structural and biochemical studies by Hong et al. show that the N-terminal region of the catalytic subunit Swr1 can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form a nucleosome by a histone chaperone mechanism.
Pituitary adenomas (PAs) are among the most common intracranial tumors. Understanding the clinical effects of various modifiable risk factors (MRFs) and nonmodifiable risk factors (NMRFs) is ...important in guiding proper treatment, yet there is limited evidence outlining the influence of MRFs and NMRFs on outcomes of PA resection. The aim of this study was to analyze MRFs and NMRFs in patients undergoing resection for PAs.
Using the 2016 and 2017 National Readmission Database, the authors identified a cohort of 9472 patients undergoing microscopic or endoscopic resection of a PA. Patients with nonoverlapping MRFs and NMRFs were analyzed for length of stay (LOS), hospital cost, readmission rates, and postoperative complications. From the original cohort, a subset of 373 frail patients (as defined by the Johns Hopkins Frailty Index) were identified and propensity matched to nonfrail patients. Statistical analysis included 1-way ANOVA, Tukey multiple comparisons of means, odds ratios, Wald testing, and unpaired Welch 2-sample t-tests to compare complications, outcomes, and costs between each cohort. Perioperative outcomes and hospital readmission rates were tracked, and predictive algorithms were developed to establish precise relationships between relevant risk factors and neurosurgical outcomes.
Malnourished patients had significantly longer LOSs when compared to nonmalnourished patients (p < 0.001). There was a significant positive correlation between the number of MRFs and readmission at 90 days (p = 0.012) and 180 days (p = 0.020). Obese patients had higher rates of postoperative neurological injury at the 30-day follow-up (p = 0.048) compared to patients with normal BMI. Within this NMRF cohort, frail patients were found to have significantly increased hospital LOS (p < 0.001) and total inpatient costs compared to nonfrail patients (p < 0.001). Predictive analytics showed that frail patients had significantly higher readmission rates at both 90-day (p < 0.001) and 180-day follow-ups (p < 0.001). Lastly, rates of acute postsurgical infection were higher in frail patients compared to nonfrail patients (p < 0.001).
These findings suggest that both MRFs and NMRFs negatively affect the perioperative outcomes following PA resection. Notable risk factors including malnutrition, obesity, elevated lipid panels, and frailty make patients more prone to prolonged LOS, higher inpatient costs, and readmission. Further prospective research with longitudinal data is required to precisely pinpoint the effects of various risk factors on the outcomes of pituitary surgery.
To date, projections of human migration induced by sea-level change (SLC) largely suggest large-scale displacement away from vulnerable coastlines. However, results from our model of Bangladesh ...suggest counterintuitively that people will continue to migrate toward the vulnerable coastline irrespective of the flooding amplified by future SLC under all emissions scenarios until the end of this century. We developed an empirically calibrated agent-based model of household migration decision-making that captures the multi-faceted push, pull and mooring influences on migration at a household scale. We then exposed ∼4800 000 simulated migrants to 871 scenarios of projected 21st-century coastal flooding under future emissions pathways. Our model does not predict flooding impacts great enough to drive populations away from coastlines in any of the scenarios. One reason is that while flooding does accelerate a transition from agricultural to non-agricultural income opportunities, livelihood alternatives are most abundant in coastal cities. At the same time, some coastal populations are unable to migrate, as flood losses accumulate and reduce the set of livelihood alternatives (so-called 'trapped' populations). However, even when we increased access to credit, a commonly-proposed policy lever for incentivizing migration in the face of climate risk, we found that the number of immobile agents actually rose. These findings imply that instead of a straightforward relationship between displacement and migration, projections need to consider the multiple constraints on, and preferences for, mobility. Our model demonstrates that decision-makers seeking to affect migration outcomes around SLC would do well to consider individual-level adaptive behaviors and motivations that evolve through time, as well as the potential for unintended behavioral responses.
Purpose
This study evaluates the influence of patient frailty status on postoperative complications in those receiving single-level lumbar fusion surgery.
Methods
The nationwide readmission database ...was retrospectively queried between 2016 and 2017 for all patients receiving single-level lumbar fusion surgery. Readmissions were analyzed at 30, 90, and 180 days from primary discharge. Demographics, frailty status, and relevant complications were queried at index admission and all readmission intervals. Complications of interest included infection, urinary tract infection (UTI), posthemorrhagic anemia, inpatient length of stay (LOS), and adjusted all-payer costs. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail control patients with similar diagnoses and procedures. The analysis used nonparametric Mann–Whitney
U
testing and odds ratios.
Results
Comparing propensity-matched cohorts revealed significantly greater LOS and total all-payer inpatient costs in frail patients than non-frail patients with comparable demographics and comorbidities (
p
< 0.0001 for both). Furthermore, frail patients encountered higher rates of UTI (OR: 3.97, 95%CI: 3.21–4.95,
p
< 0.0001), infection (OR: 6.87, 95%CI: 4.55–10.86,
p
< 0.0001), and posthemorrhagic anemia (OR: 1.94, 95%CI: 1.71–2.19,
p
< 0.0001) immediately following surgery. Frail patients had significantly higher rates of 30-day (OR: 1.24, 95%CI: 1.02–1.51,
p
= 0.035), 90-day (OR: 1.38, 95%CI: 1.17–1.63,
p
< 0.001), and 180-day (OR: 1.55, 95%CI: 1.30–1.85,
p
< 0.0001) readmissions. Lastly, frail patients had higher rates of infection at 30-day (OR: 1.61, 95%CI: 1.05–2.46,
p
= 0.027) and 90-day (OR: 1.51, 95%CI: 1.07–2.16,
p
= 0.020) readmission intervals.
Conclusions
Patient frailty status may serve as an important predictor of postoperative outcomes in patients receiving single-level lumbar fusion surgery.
Study design
Retrospective Cohort Study.
Purpose
This study evaluates the impact of patient frailty status on postoperative complications in those undergoing multi-level lumbar fusion surgery.
...Methods
The Nationwide Readmission Database (NRD) was retrospectively queried between 2016 and 2017 for patients receiving multi-level lumbar fusion surgery. Demographics, frailty status, and relevant complications were queried at index admission and readmission intervals. Primary outcome measures included perioperative complications and 30-, 90-, and 180-day complication and readmission rates. Perioperative complications of interest were infection, urinary tract infection (UTI), and posthemorrhagic anemia. Secondary outcome measures included inpatient length of stay (LOS), adjusted all-payer costs, and discharge disposition. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail patients with similar diagnoses and procedures. Subgroup analysis of minimally invasive surgery (MIS) versus open surgery within frail and non-frail cohorts was conducted to evaluate differences in surgical and medical complication rates. The analysis used nonparametric Mann–Whitney
U
testing and odds ratios.
Results
Frail patients encountered higher rates perioperative complications including posthemorrhagic anemia (OR: 1.73, 95%CI 1.50–2.00,
p
< 0.0001), infection (OR: 2.94, 95%CI 2.04–4.36,
p
< 0.0001), UTI (OR: 2.57, 95%CI 2.04–3.26,
p
< 0.0001), and higher rates of non-routine discharge (OR: 2.07, 95%CI 1.80–2.38,
p
< 0.0001). Frail patients had significantly greater LOS and total all-payer inpatient costs compared to non-frail patients (
p
< 0.0001). Frailty was associated with significantly higher rates of 90- (OR: 1.43, 95%CI 1.18–1.74,
p
= 0.0003) and 180-day (OR: 1.28, 95%CI 1.03–1.60,
p
= 0.02) readmissions along with higher rates of wound dehiscence (OR: 2.21, 95%CI 1.17–4.44,
p
= 0.02) at 90 days. Subgroup analysis revealed that frail patients were at significantly higher risk for surgical complications with open surgery (16%) compared to MIS (0%,
p
< 0.0001). No significant differences were found between surgical approaches with respect to medical complications in both cohorts, nor surgical complications in non-frail patients.
Conclusions
Frailty was associated with higher odds of all perioperative complications, LOS, and all-payer costs following multi-level lumbar fusion. Frail patients had significantly higher rates of 90 and 180-day readmission and higher rates of wound disruption at 90-days. On subgroup analysis, MIS was associated with significantly reduced rates of surgical complications specifically in frail patients. Our results suggest frailty status to be an important predictor of perioperative complications and long-term readmissions in geriatric patients receiving multi-level lumbar fusions. Frail patients should undergo surgery utilizing minimally invasive techniques to minimize risk of surgical complications. Future studies should explore the utility of implementing frailty in risk stratification assessments for patients undergoing spine surgery.
Leaf protein can be obtained cost-efficiently by alkaline extraction, but overuse of chemicals and low quality of (denatured) protein limits its application. The research objective was to investigate ...how alkali aids protein extraction of green tea leaf residue, and use these results for further improvements in alkaline protein biorefinery. Protein extraction yield was studied for correlation to morphology of leaf tissue structure, protein solubility and hydrolysis degree, and yields of non-protein components obtained at various conditions. Alkaline protein extraction was not facilitated by increased solubility or hydrolysis of protein, but positively correlated to leaf tissue disruption. HG pectin, RGII pectin, and organic acids were extracted before protein extraction, which was followed by the extraction of cellulose and hemi-cellulose. RGI pectin and lignin were both linear to protein yield. The yields of these two components were 80% and 25% respectively when 95% protein was extracted, which indicated that RGI pectin is more likely to be the key limitation to leaf protein extraction. An integrated biorefinery was designed based on these results.
Active patients with displaced femoral neck fractures are often treated with total hip arthroplasty (THA). However, optimal femoral fixation in these patients is controversial. The purpose of this ...study was to compare early complication and readmission rates in patients with hip fracture treated with THA receiving cemented vs cementless femoral fixation.
The National Readmissions Database was queried to identify patients undergoing primary THA for femoral neck fracture from 2016 to 2017. Postoperative complications and unplanned readmissions at 30, 90, and 180 days were compared between patients treated with cemented and cementless THA. Univariate and multivariate analyses were performed to compare differences between groups and account for confounding variables.
Of 17,491 patients identified, 4427 (25.3%) received cemented femoral fixation and 13,064 (74.7%) cementless. The cemented group was significantly older (77.2 vs 71.1, P < .001), had more comorbidities (Charlson comorbidity index: 4.44 vs 3.92, P < .001), and had a greater proportion of women (70.5% vs 65.2%, P < .001) compared with the cementless group. On multivariate analysis, cemented fixation was associated with reduced rates of periprosthetic fracture (odds ratio: 0.052, 95% confidence interval: 0.003-0.247, P = .004) at 30 days but similar readmission rates at 30, 90, and 180 days (odds ratio range: 1.012-1.114, P > .05) postoperatively compared with cementless fixation. Cemented fixation was associated with greater odds of medical complications at 180 days postoperatively (odds ratio:: 1.393, 95% confidence interval: 1.042-1.862, P = .025).
Cemented femoral fixation was associated with a lower short-term incidence of periprosthetic fractures, higher incidence of medical complications, and equivalent unplanned readmission rates within 180 days postoperatively compared with cementless fixation in patients undergoing THA for femoral neck fracture.
Level III.
Humans routinely deal with both traditional and novel risks. Different kinds of risks have been a driving force for both evolutionary adaptations and personal development. This study explored the ...genetic and environmental influences on human risk taking in different task domains. Our approach was threefold. First, we integrated several scales of domain-specific risk-taking propensity and developed a synthetic scale, including both evolutionarily typical and modern risks in the following 7 domains: cooperation/competition, safety, reproduction, natural/physical risk, moral risk, financial risk, and gambling. Second, we conducted a twin study using the scale to estimate the contributions of genes and environment to risk taking in each of these 7 domains. Third, we conducted a series of meta-analyses of extant twin studies across the 7 risk domains. The results showed that individual differences in risk-taking propensity and its consistency across domains were mainly regulated by additive genetic influences and individually unique environmental experiences. The heritability estimates from the meta-analyses ranged from 29% in financial risk taking to 55% in safety. Supporting the notion of risk-domain specificity, both the behavioral and genetic correlations among the 7 domains were generally low. Among the relatively few correlations between pairs of risk domains, our analysis revealed a common genetic factor that regulates moral, financial, and natural/physical risk taking. This is the first effort to separate genetic and environmental influences on risk taking across multiple domains in a single study and integrate the findings of extant twin studies via a series of meta-analyses conducted in different task domains.
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