bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative Sedative-hypnotic Medication Use and Adverse Postoperative Outcomes
Authors: Gaulton Timothy G. , Wunsch Hannah , Gaskins Lakisha J. , Leonard Charles E. , Hennessy Sean , Ashburn Michael , Brensinger Colleen , Newcomb Craig , Wijeysundera Duminda , Bateman Brian T. , Bethell Jennifer , Neuman Mark D. 
Published: August 2019

Objective:
To determine the association between preoperative benzodiazepine and nonbenzodiazepine receptor agonist (“Z-drugs”) use and adverse outcomes after surgery.

Background:
Prescriptions for benzodiazepines and Z-drugs have increased over the past decade. Despite this, the association of preoperative benzodiazepines and Z-drug receipt with adverse outcomes after surgery is unknown.

Methods:
Using the Optum Clinformatics Datamart, we performed a retrospective cohort study of adults 18 years or older who underwent any of 10 common surgical procedures between 2010 and 2015. The principal exposure was one or more filled prescriptions for a benzodiazepine or Z-drug in the 90 days before surgery. The primary outcome was any emergency department visit or hospital admission for either (1) a drug related adverse medical event or overdose or (2) a traumatic injury in the 30 days after surgery.

Results:
Of 785,346 patients meeting inclusion criteria, 94,887 (12.1%) filled a preoperative prescription for a benzodiazepine or Z-drug. From multivariable logistic regression, benzodiazepine or Z-drug use was associated with an increased odds of an adverse postoperative event [odds ratio 1.13; 95% confidence interval: 1.08–1.18). In a separate regression, coprescription of benzodiazepines or Z-drugs with opioids was associated with a 1.45 odds of an adverse postoperative event (95% confidence interval: 1.37–1.53).

Conclusions:
Preoperative benzodiazepines and Z-drug use is common and associated with increased odds of adverse outcomes after surgery, particularly when coprescribed with opioids. Counseling on appropriate benzodiazepine and Z-drug use in advance of elective surgery may potentially increase the safety of surgical care.
Randomized Comparison of Gastric Tube Reconstruction With and Without Duodenal Diversion Plus Roux-en-Y Anastomosis After Esophagectomy
Authors: Yano Masahiko , Sugimura Keijiro , Miyata Hiroshi , Motoori Masaaki , Tanaka Koji , Omori Takeshi , Ohue Masayuki , Sakon Masato 
Published: August 2019

Objective:
This prospective randomized phase-II trial examined whether gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis(RY) minimized gastroduodenal reflux and delayed gastric emptying compared with standard gastric reconstruction.

Summary Background Data:
There is no established standard surgical procedure to prevent both gastroduodenal reflux and delayed gastric emptying simultaneously.

Methods:
Sixty patients with thoracic esophageal cancer scheduled to undergo esophagectomy with retrosternal gastric tube reconstruction were randomly allocated to standard gastric reconstruction (non-RY, n = 31) or gastric reconstruction with duodenal diversion plus RY (n = 29) groups. Primary endpoint was quality of life assessed by DAUGS-32 score 1 year after surgery. Secondary endpoints were the extent of postoperative duodenal juice reflux into the gastric tube, postoperative morbidity, endoscopic findings, body weight changes, and nutritional status.

Results:
Preoperative clinicopathological characteristics and postoperative morbidity did not differ significantly between groups. However, operation time and blood loss volume were significantly higher in the RY group. Pancreatic amylase concentrations in the gastric conduit on postoperative days 2, 3, and 7 were higher in the non-RY group. Postoperative endoscopic examination showed residual gastric content in 7 of 17 patients in the non-RY group but in none in the RY group (P = 0.012). Quality of life was significantly favorable in the RY group with regard to reflux symptoms and food passage dysfunction. Postoperative body weight changes, serum albumin levels, and peripheral blood lymphocyte counts were not significantly different between groups.

Conclusion:
Gastric reconstruction with duodenal diversion plus RY is effective in improving both gastroduodenal reflux and delayed gastric emptying.
Donor-recipient Sex Differences Do Not Affect Survival Outcomes After Kidney Transplantation: A Population Cohort Study
Authors: Morgan Georgia , Goolam-Mahomed Zahrah , Hodson James , Nath Jay , Sharif Adnan 
Published: August 2019

Background.Donor factors can influence decision making for organ utilization for potential kidney transplant candidates. Prior studies exploring the effect of donor-recipient sex matching on kidney transplant outcomes have reported heterogenous and conflicting results. The aim of this contemporary population-cohort analysis was to explore the effect of donor-recipient sex matching on kidney transplant outcomes in the United Kingdom.Methods.In this retrospective, observational study, we analyzed all patients receiving kidney-alone transplants between 2003 and 2018 using UK Transplant Registry data. Stratified by recipient sex, outcomes were compared between male and female donors with univariable/multivariable analyses.Results.Data were analyzed for 25 140 recipients. Of these, 13 414 (53.4%) of kidneys were from male donors and 15 690 (62.4%) of recipients were male. The odds of initial graft dysfunction (delayed graft function/primary nonfunction) were significantly lower for female donor kidneys transplanted into both male (adjusted odds ratio = 0.89, 95% confidence interval [CI] = 0.80-0.98,P = 0.019) and female (adjusted odds ratio = 0.81, 95% CI = 0.71-0.93,P = 0.003) recipients. Male recipients of female donor kidneys had creatinine levels at 1 year that were 6.3% higher (95% CI = 4.8%-7.7%,P < 0.001) than male recipients of male donor kidneys, with a similar sex difference of 4.1% (95% CI = 2.1%-6.1%,P < 0.001) observed within female recipients. However, neither patient nor graft survival was found to differ significantly by donor sex on either univariable or multivariable analysis.Conclusions.Our data provide contemporary data on sex mismatch for recipient counseling and reassurance with regards to equivalent long-term clinical outcomes based upon donor sex.
Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis
Authors: Saeed Naba , Glass Lisa , Sharma Pratima , Shannon Carol , Sonnenday Christopher J. , Tincopa Monica A. 
Published: August 2019

Background.
The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT.

Methods.
MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale.

Results.
Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes.

Conclusions.
There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.
Continent-wide effects of urbanization on bird and mammal genetic diversity
Authors: Schmidt C. , Domaratzki M. , Kinnunen R.P. , Bowman J. , Garroway C.J. 
Published: August 2019

AbstractUrbanization and associated environmental changes are causing global declines in vertebrate populations. In general, population declines of the magnitudes now detected should lead to reduced effective population sizes for animals living in proximity to humans and disturbed lands. This is cause for concern because effective population sizes set the rate of genetic diversity loss due to genetic drift, the rate of increase in inbreeding, and the efficiency with which selection can act on beneficial alleles. We predicted that the effects of urbanization should decrease effective population size and genetic diversity, and increase population-level genetic differentiation. To test for such patterns, we repurposed and reanalyzed publicly archived genetic data sets for North American birds and mammals. After filtering, we had usable raw genotype data from 85 studies and 41,023 individuals, sampled from 1,008 locations spanning 41 mammal and 25 bird species. We used census-based urban-rural designations, human population density, and the Human Footprint Index as measures of urbanization and habitat disturbance. As predicted, mammals sampled in more disturbed environments had lower effective population sizes and genetic diversity, and were more genetically differentiated from those in more natural environments. There were no consistent relationships detectable for birds. This suggests that, in general, mammal populations living near humans may have less capacity to respond adaptively to further environmental changes, and be more likely to suffer from effects of inbreeding.
Effect of systemic treatment with N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3- carboxamide (HIOC) or tauroursodeoxycholic Acid (TUDCA) on retinal ganglion cell death following optic nerve crush
Authors: Li Ying , Zhang Xian , Wang Jiaxing , Sellers Jana T. , Boyd Amber P. , Nickerson John M. , Boatright Jeffrey H. 
Published: August 2019

AbstractThe aim of this study was to investigate the protective effects of systemically administered N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) or tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model. HIOC (50 mg/kg) or TUDCA (500mg/kg) were intraperitoneally (i.p.) injected into adult C57BL/6 mice three times per week. Two weeks after treatment (6 injections), unilateral optic nerve crush was conducted followed by treatment at the same day. The treatment was continued until 1 week or 2 weeks after ONC. A control cohort was identically treated with drug vehicle (phosphate-buffered saline; PBS). Retinas were harvested for whole mount immunofluorescence staining with RGC markers and imaged by fluorescent confocal microscopy at 40x magnification. Fluorescing cells were counted by computer-assisted automated identification and counting software (CellProfiler). Cohort sampling sizes were N=4 and statistical tesing was by the Wilcoxon-Mann-Whitney Test. Significant loss (80%’85%) occurred in the PBS-injected group 1 and 2 weeks after ONC. This loss was partially but significantly prevented in drug-treated cohorts (P < 0.05). Delivery of HIOC or TUDCA by i.p. injection increased survival of RGCs after ONC. Protection was similar between treatment with either drug. These data suggest that it is worthwhile to further explore possible protective effects of HIOC or TUDCA on RGC subtypes with regards to structure and function and in additional disease models that involve RGC loss.
Related enteric viruses have different requirements for host microbiota in mice
Authors: Robinson Christopher M. , Acevedo Mikal A. Woods , McCune Broc T. , Pfeiffer Julie K. 
Published: August 2019

AbstractAccumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, like poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. Quantity and composition of bacterial communities were altered by treatment with the five antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis, while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 is more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ in their reliance on microbiota.ImportanceRecent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that microbiota can influence enteric virus infection through distinct mechanisms, even for closely related viruses.
Physical limit to concentration sensing in a changing environment
Authors: Mora Thierry , Nemenman Ilya 
Published: August 2019

AbstractCells adapt to changing environments by sensing ligand concentrations using specific receptors. The accuracy of sensing is ultimately limited by the finite number of ligand molecules bound by receptors. Previously derived physical limits to sensing accuracy have assumed that the concentration was constant and ignored its temporal fluctuations. We formulate the problem of concentration sensing in a strongly fluctuating environment as a non-linear field-theoretic problem, for which we find an excellent approximate Gaussian solution. We derive a new physical bound on the relative error in concentration c which scales as δc/c ~ (Dacτ)−1/4 with ligand diffusivity D, receptor cross-section a, and characteristic fluctuation time scale τ, in stark contrast with the usual Berg and Purcell bound δc/c ~ (DacT)−1/2 for a perfect receptor sensing concentration during time T. We show how the bound can be achieved by a simple biochemical network downstream the receptor that adapts the kinetics of signaling as a function of the square root of the sensed concentration.
Culture of salivary methanogens assisted by chemically produced hydrogen
Authors: Guindo CO , Terrer E , Chabrière E , Aboudharam G , Drancourt M , Grine G 
Published: August 2019

ABSTRACTMethanogen cultures require hydrogen produced by fermentative bacteria such asBacteroides thetaiotaomicron(biological method). We developed an alternative method for hydrogen production using iron filings and acetic acid with the aim of cultivating methanogens more efficiently and more quickly (chemical method). We developed this new method with a reference strain ofMethanobrevibacter oralis, compared the method to the biological reference method with a reference strain ofMethanobrevibacter smithiiand finally applied the method to 50 saliva samples. Methanogen colonies counted using ImageJ software were identified using epifluorescence optical microscopy, real-time PCR and PCR sequencing. For cultures containing the pure strains ofM. oralisandM. smithii, colonies appeared three days postinoculation with the chemical method versus nine days with the biological method. The average number ofM. smithiicolonies was significantly higher with the chemical method than with the biological method. There was no difference in the delay of observation of the first colonies in the saliva samples between the two methods. However, the average number of colonies was significantly higher when using the biological method than when using the chemical method at six days and nine days postinoculation (Student’s test, p = 0.005 and p = 0.04, respectively). The chemical method made it possible to isolate four strains ofM. oralisand three strains ofM. smithiifrom the 50 saliva samples. Establishing the chemical method will ease the routine isolation and culture of methanogens.
Kcnn3 as a target for treating aberrant behaviors in stressed, ethanol-dependent mice
Authors: Padula Audrey E. , Rinker Jennifer A. , Khan Fauzan , Lopez Marcelo F. , Mulligan Megan K. , Williams Robert W. , Becker Howard C. , Mulholland Patrick J. 
Published: August 2019

AbstractAnxiety and mood disorders are often comorbid with alcohol use disorder (AUD) and are considered critical in the development, maintenance, and reinstatement of alcohol dependence and harmful alcohol-seeking behaviors. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy ethanol drinking and anxiety-related behaviors. We used a model of stress-induced escalation of drinking in ethanol dependent C57BL/6J mice to measure anxiety-like behaviors on the marble burying and novelty-suppressed feeding task (NSFT) during abstinence. In order to identify novel pharmacogenetic targets that may lead to more effective treatment, a targeted bioinformatics analysis was used to quantify the expression of K+ channel genes in the amygdala that covary with anxiety-related phenotypes in the well phenotyped and fully sequenced family of BXD strains. A pharmacological approach was used to validate the key bioinformatics finding in ethanol-dependent, stressed C57BL/6J mice during the NSFT. Amygdalar expression of Kcnn3 correlated significantly with just over 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for anxiety-like behaviors in this family. Kcnn3 expression in the amygdala correlated negatively with binge-like and voluntary ethanol drinking. C57BL/6J mice treated with chronic intermittent ethanol exposure and repeated swim stress consumed more ethanol in their home cages and showed hypophagia on the NSFT during prolonged abstinence. Pharmacologically targeting KCNN3 protein with the KCa2 channel positive modulator 1-EBIO decreased ethanol drinking and reduced latency to approach food during the NSFT in ethanol-dependent, stressed mice. Collectively these validation studies provide central nervous system mechanistic links into to the covariance of stress, anxiety, and AUD in the BXD strains. Further this analytical approach is effective in defining targets for treating alcohol dependence and comorbid mood and anxiety disorders.
Molecular Mechanism of Action of Mitochondrial Therapeutic SS-31 (Elamipretide): Membrane Interactions and Effects on Surface Electrostatics
Authors: Mitchell Wayne , Ng Emily A. , Tamucci Jeffrey D. , Boyd Kevin , Sathappa Murugappan , Coscia Adrian , Pan Meixia , Han Xianlin , Eddy Nicholas A. , May Eric R. , Szeto Hazel H. , Alder Nathan N. 
Published: August 2019

AbstractMitochondrial dysfunction includes heritable diseases, acquired pathologies, and age-related declines in health. Szeto-Schiller (SS) peptides comprise a class of amphipathic tetrapeptides that have demonstrated efficacy in treating a wide array of mitochondrial disorders, and are believed to target mitochondrial membranes due to their enrichment in the anionic phospholipid cardiolipin (CL). However, little is known regarding how SS peptides interact with or alter the physical properties of lipid bilayers. In this study, we have analyzed the interactions of the lead compound SS-31 (Elamipretide) with model and mitochondrial membranes using biophysical and computational approaches. Our results show that this polybasic peptide partitions into the membrane interfacial region with affinity and binding density that are directly related to surface charge. SS-31 binding does not destabilize lamellar bilayers even at the highest binding concentrations; however, it does cause saturable alterations in lipid packing. Most notably, SS-31 modulates the surface electrostatic properties of model and mitochondrial membranes, which could play a significant role in the mitoprotective properties of this compound. As a proof of concept, we show that SS-31 alters ion distribution at the membrane interface with implications for maintaining mitochondrial membranes subject to divalent cation (calcium) stress. Taken together, these results support a mechanism of action in which SS peptides interact with lipid bilayers and alter the biophysical (primarily electrostatic) properties of mitochondrial membranes as their primary mechanism of action. Understanding this molecular mechanism is key to the development of future compound variants with enhanced efficacy.SignificanceSzeto-Schiller (SS) peptides are among the most promising therapeutic compounds for mitochondrial dysfunction. However, the molecular target(s) and the mechanism of action of SS peptides are poorly understood. In this study, we evaluate the interaction of the lead compound SS-31 (Elamipretide) with mitochondrial and synthetic model membranes using a host of biophysical techniques. Our results show that SS-31 membrane interaction is driven largely by the negative surface charge of mitochondrial membranes and that SS-31 alters lipid bilayer properties, most notably electrostatics at the membrane interface. This work supports a mechanism in which SS peptides act on a key physical property of mitochondrial membranes rather than with a specific protein complex, consistent with the exceptionally broad therapeutic efficacy of these compounds.