bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined General and Epidural Anesthesia is Associated With Decreased Opioid Consumption and Enhanced Pain Control After Penile Inversion Vaginoplasty in Transwomen
Authors: Salgado Christopher J. , Gonzalez Daisy I. , Wolfe Erin M. , Balise Raymond R. , Gebhard Ralf E. , Kamisetti Seema , Ovadia Steven 
Published: August 2019

Background
Penile skin inversion vaginoplasty is a gender-affirming surgical procedure for transwomen with limited surgical analgesic protocol. This study compares the postoperative pain and opioid use in patients managed for surgery with general anesthesia (GA) with patients who were given combined epidural and general anesthesia (E/GA) with continuing postoperative epidural analgesia.

Methods
All patients who underwent penile inversion vaginoplasty between May of 2016 and May of 2018 under the care of single surgeon were identified retrospectively, 18 patients of which met the inclusion criteria. A retrospective chart review was conducted. Outcome measures were postoperative pain using visual analog scale, type and dosage of postoperatively administered intravenous or oral opioids (converted to morphine milligram equivalents, duration of inpatient admission, and time to ambulation.

Results
Patients who received combined E/GA reported significantly less pain and used less opioids during the first 4 postoperative days in comparison with patients who received GA alone. The reduction in mean pain associated with the use of an epidural was found to be statistically significant (P < 0.0005) as was the difference in opioid used in the 2 groups (P < 0.005) over the first 4 days postoperatively. Differences in day 5 pain suggest that postoperative pain is significantly lower even after the epidural has been removed (P < 0.005). There was no significant difference in length of hospital stay and time to ambulation (P > 0.05).

Conclusions
Combined E/GA was associated with decreased inpatient opioid consumption after surgery and provided superior pain control than administration of GA alone. Based on these findings, combined E/GA should be strongly considered for patients undergoing penile inversion vaginoplasty.
SIRT1 Mediates Septic Cardiomyopathy in a Murine Model of Polymicrobial Sepsis
Authors: Smith Lane M. , Yoza Barbara K. , Hoth J. Jason , McCall Charles E. , Vachharajani Vidula 
Published: August 2019

ABSTRACT

Background:
Cardiac dysfunction, a common complication from severe sepsis, is associated with increased morbidity and mortality. However, the molecular mechanisms of septic cardiac dysfunction are poorly understood. SIRT1, a member of the sirtuin family of NAD+-dependent protein deacetylases, is an important immunometabolic regulator of sepsis, and sustained SIRT1 elevation is associated with worse outcomes and organ dysfunction in severe sepsis. Herein, we explore the role of SIRT1 in septic cardiac dysfunction using a murine model of sepsis.

Methods:
An in vitro model of inflammation in isolated H9c2 cardiomyocytes was used to confirm SIRT1 response to stimulation with lipopolysaccharide (LPS), followed by a murine model of cecal ligation and puncture (CLP) to investigate the molecular and echocardiographic response to sepsis. A selective SIRT1 inhibitor, EX-527, was employed to test for SIRT1 participation in septic cardiac dysfunction.

Results:
SIRT1 mRNA and protein levels in cultured H9c2 cardiomyocytes were significantly elevated at later time points after stimulation with LPS. Similarly, cardiac tissue harvested from C57BL/6 mice 36 h after CLP demonstrated increased expression of SIRT1 mRNA and protein compared with sham controls. Administration of EX-527 18 h after CLP reduced SIRT1 protein expression in cardiac tissue at 36 h. Moreover, treatment with EX-527 improved cardiac performance with increased global longitudinal strain and longitudinal strain rate.

Conclusions:
Our findings reveal that SIRT1 expression increases in isolated cardiomyocytes and cardiac tissue after sepsis inflammation. Moreover, rebalancing SIRT1 excess in late sepsis improves cardiac performance, suggesting that SIRT1 may serve as a therapeutic target for septic cardiomyopathy.
From cachexia to obesity: the role of host metabolism in cancer immunotherapy
Authors: Brocco Davide , Di Marino Pietro , Grassandonia Antonino 
Published: August 2019

Purpose of review
Currently, several clinical trials in cancer therapy have demonstrated the success of immunomodulatory therapies. However, only a variable fraction of patients actually benefit from these treatments. The understanding of key mechanisms behind this response heterogeneity is one of the major unmet need and intense research field in immuno-oncology. This review will discuss the host metabolic dysfunctions derived from cachexia or obesity that can affect the response to cancer immunotherapy.

Recent findings
Preclinical studies demonstrated that chronic inflammation, nutritional intake impairment and endocrine dysfunction may affect anticancer innate and adaptive immunity, both in cachexia and obesity. New emerging clinical findings have highlighted the impact of metabolic biomarkers in predicting response to immune checkpoint inhibitors in cancer patients.

Summary
Patient's weight and inflammatory status could be relevant in the clinical decision-making process before starting cancer immunotherapy and for an effective patient selection and stratification in future clinical trials employing this class of anticancer agents.
It's About Time: Transfusion effects on postinjury platelet aggregation over time
Authors: Kornblith Lucy Z. , Decker Anna , Conroy Amanda S. , Hendrickson Carolyn M. , Fields Alexander T. , Robles Anamaria J. , Callcut Rachael A. , Cohen Mitchell J. 
Published: August 2019

BACKGROUND
Impaired postinjury platelet aggregation is common, but the effect of transfusion on this remains unclear. Data suggest that following injury platelet transfusion may not correct impaired platelet aggregation, and impaired platelet aggregation may not predict the need for platelet transfusion. We sought to further investigate platelet aggregation responses to transfusions, using regression statistics to isolate the independent effects of transfusions given in discrete time intervals from injury on both immediate and longitudinal platelet aggregation. We hypothesized that platelet aggregation response to platelet transfusion increases over time from injury.

METHODS
Serial (0–96 hours) blood samples were collected from 248 trauma patients. Platelet aggregation was assessed in vitro with impedance aggregometry stimulated by adenosine diphosphate, collagen, and thrombin receptor-activating peptide-6. Using regression, transfusion exposure was modeled against platelet aggregation at each subsequent timepoint and adjusted for confounders (Injury Severity Score, international normalized ratio (INR), base deficit, platelet count, and interval transfusions). The expected change in platelet aggregation at each timepoint under the intervention of transfusion exposure was calculated and compared with the observed platelet aggregation.

RESULTS
The 248 patients analyzed were severely injured (Injury Severity Score, 21 ± 19), with normal platelet counts (mean, 268 × 109/L ± 90), and 62% were transfused in 24 hours. The independent effect of transfusions on subsequent platelet aggregation over time was modeled with observed platelet aggregation under hypothetical treatment of one unit transfusion of blood, plasma, or platelets. Platelet transfusions had increasing expected effects on subsequent platelet aggregation over time, with the maximal expected effect occurring late (4–5 days from injury).

CONCLUSION
Controversy exists on whether transfusions improve impaired postinjury platelet aggregation. Using regression modeling, we identified that expected transfusion effects on subsequent platelet aggregation are maximal with platelet transfusion given late after injury. This is critical for tailored resuscitation, identifying a potential early period of resistance to platelet transfusion that resolves by 96 hours.

LEVEL OF EVIDENCE
Therapeutic, level V.
Cold-stored whole blood: A better method of trauma resuscitation?
Authors: Hazelton Joshua Paul , Cannon Jeremy W. , Zatorski Catherine , Roman Janika San , Moore Sarah A. , Young Andrew J. , Subramanian Madhu , Guzman Jessica F. , Fogt Franz , Moran Anna , Gaughan John , Seamon Mark J. , Porter John 
Published: August 2019

BACKGROUND
Cold-stored whole blood (CWB) provides a balance of red blood cells, plasma, and platelets in less anticoagulant volume than standard blood component therapy (BCT). We hypothesize that patients receiving CWB along with BCT have improved survival compared with patients receiving only BCT.

METHODS
We performed a dual-center case-match study of trauma patients who received CWB and BCT at two urban, Level-I Trauma Centers. Criteria to receive CWB included boys 16 years of older, women older than 50 years, SBP less than 90 mm Hg, and identifiable source of hemorrhage. We performed a 2:1 propensity match against any trauma patient who received 1 unit or greater of packed red cells during their initial trauma bay resuscitation. Endpoints included trauma bay mortality, 30-day mortality, laboratory values at 4 hours and 24 hours, and overall blood product utilization. Comparisons were made with Wilcoxon-ranked sum and Fisher's exact test, p less than 0.05 was significant.

RESULTS
Between both institutions, a total of 107 patients received CWB during the study period with 91 being matched to 182 BCT patients for analysis. Hemodynamic parameters of the patients in both groups at the time of presentation were similar. The CWB patients had higher mean hemoglobin (10 ± 2 g/dL vs. 11 ± 2 g/dL; p < 0.001) and hematocrit (29.2 ± 6.1% vs. 32.1 ± 5.8%; p < 0.001) at 24 hours. Importantly, trauma bay mortality was less in CWB patients (8.8% vs. 2.2%;p = 0.039). Thirty-day mortality was not different in CWB patients, and there were no differences in the total amount of blood products transfused at the 4-hour and 24-hour periods.

CONCLUSION
Cold-stored whole blood offers the benefit of a balanced resuscitation with improved trauma bay survival and higher mean hemoglobin at 24 hours. A larger, prospective study is needed to determine whether it has a longer-term survival benefit for severely injured patients.

LEVEL OF EVIDENCE
Therapeutic, level III.
Differential expression of Ormdl genes in the islets of mice and humans with obesity
Authors: Fenske Rachel , Lee Hugo , Akcan Tugce , Domask Elliot , Davis Dawn Belt , Kimple Michelle , Engin Feyza 
Published: August 2019

SummaryThe orosomucoid-like proteins (Ormdl1-3) are emerging as the critical regulators of sphingolipid homeostasis, inflammation and ER stress. However, their roles in β-cells and obesity remain unknown. Here, we showed that islets isolated from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression while ORMDL3 expression was significantly reduced as compared to islets from lean donors. In contrast, Ormdl3 expression was significantly upregulated in the islets of leptin-deficient obese (ob/ob) mice compared to lean mice. We identified that the difference in expression of Ormdl3 between mouse and human islets was leptin-dependent, as treatment of ob/ob mice with leptin significantly reduced Ormld3 expression. Furthermore, Ormdl1-3 were significantly upregulated upon chemically-induced ER stress, but they showed differential responsiveness to cytokines in a β-cell line. Knockdown of Ormdl3 substantially increased expression of apoptotic markers, which was rescued by a pharmacological inhibitor of ceramide synthase. Taken together we demonstrate leptin-dependent regulation of Ormdl3 expression in ob/ob islets, highlight the possible importance of β-cell stress conditions in differential Ormdl expression and identify a critical role for Ormdl3 in β-cell survival.
Residual feed intake in dairy ewes: an evidence of intraflock variability
Authors: González-García E. , Santos J. P. Dos , Hassoun P. 
Published: August 2019

AbstractThis study examined the intraflock variability of feed efficiency in dairy ewes, through monitoring residual feed intakes (RFI). Primiparous lactating ewes (n=43; 57.7±0.91 kg body weight [BW] at lambing), representative of a French Lacaune dairy flock, were allocated in an equilibrated 2 × 2 factorial design experiment, lasting for 63 days during mid-lactation and combining 2 litter sizes (singletons, SING or twins, TWIN) and 2 daily milking frequencies (once, ONE or twice, TWO). Ewes were individually fed a diet based on ryegrass silage, local hay and supplements. Individual DMI was recorded daily and further used to evaluate (and compare) differences in RFI between ewes at 35, 42, 49, 56, 63, 70, 77, 84, 91 and 98 days relative to lambing (DIM). Total (BW) and metabolic (BW0.75) body weight, BCS, milk yield and plasma NEFA were monitored weekly. Differences in DMI were mainly due to the lactation stage and litter size and were 11% higher in ewes with TWIN compared to SING. This was positively correlated to milk yield and consistent with differences in RFI which varied due to litter size and to the milking frequency × lactation stage interaction. Ewes that lambed SING showed higher feed efficiency (□0.13±0.020 vs. 0.08±0.015 kg DM/ewe/d of RFI in SING vs. TWIN, respectively), whereas there was no differences in BW or BCS. Milking frequency did not affect DMI but milk yields were higher in TWO, which was related to a higher feed efficiency in this group (0.04±0.017 vs. □0.10±0.018 kg DM/ewe/d of RFI in ONE vs. TWO, respectively). Average RFI was affected (P <0.0001) by the ewe, thus allowing a ranking among individuals to be established. High (n=22) or low (n=21) feed efficiency ewes averaged □0.17±0.09 or 0.18±0.09 kg DM/d RFI, respectively. Estimates of RFI were not correlated to the individual milk production potential. Even if no differences in BW, BW0.75 or BCS were detected, high efficiency ewes mobilised almost two-fold their body reserves when compared to the low efficiency group. The observed intraflock variability in feed efficiency of this dairy ewes flock was affected by litter size and milking frequency but also by evident differences between individuals’ physiologies.
Short-, medium- and long-term metabolic responses of adult ewes submitted to nutritional and β-adrenergic challenges
Authors: González-García Eliel , Alhamada Moutaz , Debus Nathalie , Menassol Jean-Baptiste , Tesnière Anne , Vero Jéssica Gonçalves , Barboza Bruna , Bocquier François 
Published: August 2019

AbstractBackgroundIn order to maintain homeostasis, ruminants submitted to alternating shortage and refeeding situations manifest switches in metabolic pathways induced by undernutrition and body reserves (BR) replenishment cycles. The objective of this experiment was to study adaptive regulatory mechanisms present during subsequent feeding transition periods and the inherent lipolytic activity of the adipose tissue in individuals with contrasted BR. Three diets containing different levels of energy were offered to 36 mature, dry, non-pregnant Mérinos d’Arles ewes in an experiment lasting 122 days. Ewes were selected with similar body weight (BW), body condition score (BCS) and were allocated into three equivalent treatments according to the plane of nutrition: normally fed (Control); underfed (Under) or overfed (Over). The BW, BCS and individual energy metabolism were monitored. At the end of the experiment, lipolytic activity of adipose tissue was studied through a ß-adrenergic challenge to the same ewes, with body conditions according to the offered diet (Normal, Leans and Fat, respectively).ResultsAnabolic or catabolic responses to energy dietary manipulation were accompanied by synchronised metabolic regulation, leading to contrasting metabolic and BR profiles. Average BW and BCS were higher and lower in Over and Under ewes, respectively. The higher and lower BR variations were observed for Under and Over ewes. Higher plasma non-esterified fatty acids (NEFA) concentrations were accompanied by lower insulin, leptin and glucose. Differences in leptin were consistent with the dietary energy load (Over > Control > Under). After refeeding, a rebound in BW and BCS was observed for the three groups whereas NEFA was drastically reduced in Under ewes. No differences among treatments were detected in NEFA profiles at the end of the study but lipolytic activity responses to the ß - adrenergic challenge were different and coherent with the adipose tissue mass (Fat > Normal > Lean) and, importantly, was also different between ewes from the same group or BR status, thus evidencing diversity among individual adaptive capacities.ConclusionsThe ability of ewes to quickly overcome undernutrition situations by efficiently using their BR was confirmed. There is potential for a simplified ß-adrenergic challenge protocol helping to identify differences in adaptive capacity among individuals.
Sensory information from a slipping object elicits a rapid and automatic shoulder response
Authors: Hernandez-Castillo Carlos R. , Maeda Rodrigo S. , Pruszynski J. Andrew , Diedrichsen Jörn 
Published: August 2019

ABSTRACTHumans have the remarkable ability to hold, grasp, and manipulate objects. Previous work has reported rapid and coordinated reactions in hand and shoulder muscles in response to external perturbations to the arm during object manipulation; however, little is known about how somatosensory feedback of an object slipping in the hand influences responses of the arm. We built a hand-held device to stimulate the sensation of slipping at all five fingertips. The device was integrated into an exoskeleton robot that supported it against gravity. The setup allowed us to decouple somatosensory stimulation in the fingers from forces applied to the arm— two variables that are highly interdependent in real-world scenarios. Fourteen participants performed three experiments in which we measured their arm feedback responses during slip stimulation. Slip stimulations were applied horizontally, in one of two directions, and participants were either instructed to follow the slip direction, or to move the arm in the opposite direction. Participants showed responses within ∼67 ms of slip onset when following the direction of slip, but significantly slower responses when instructed to move in the opposite direction. Arm responses were modulated by the speed but not the distance of the slip. Finally, when slip stimulation was combined with mechanical perturbations to the arm, we found that sensory information from the fingertips significantly modulated the shoulder feedback response. Overall, the results demonstrate the existence of a rapid feedback system that stabilizes hand-held objects.NEW & NOTHEWORTHYWe tested whether the sensation of an object slipping from the fingers modulates shoulder feedback responses. We found rapid shoulder feedback responses when participants were instructed to follow the slip direction with the arm. Shoulder responses following mechanical joint perturbations were also potentiated when combined with slipping. These results demonstrate the existence of fast and automatic feedback responses in the arm in reaction to sensory input to the fingertips that maintain grip on hand-held objects.
Brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice
Authors: Carson Caryn , Macias-Velasco Juan F , Gunawardana Subhadra , Miranda Mario A , Oyama Sakura , Schmidt Heather , Wayhart Jessica P , Lawson Heather A 
Published: August 2019

AbstractDisruption of glucose homeostasis increases the risk of type II diabetes, cardiovascular disease, stroke, and cancer. We leverage a novel rodent model, the SM/J mouse, to understand glycemic control in obesity. On a high fat diet, obese SM/J mice initially develop impaired glucose tolerance and elevated fasting glucose. Strikingly, their glycemic dysfunction resolves by 30 weeks of age despite persistence of obesity. A prominent phenotype is that they dramatically expand their brown adipose depots as they resolve glycemic dysfunction. This occurs naturally and spontaneously on a high fat diet, with no temperature or genetic manipulation. When the brown adipose depot is removed from normoglycemic obese mice, fasting blood glucose and glucose tolerance revert to unhealthy levels, and animals become insulin resistant. We identified 267 genes whose expression changes in the brown adipose when the mice resolve their unhealthy glycemic parameters, and find the expanded tissue has a ‘healthier’ expression profile of cytokines and extracellular matrix genes. We describe morphological, physiological, and transcriptomic changes that occur during the unique brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice. Understanding this phenomenon in mice will open the door for innovative therapies aimed at improving glycemic control in obesity.Significance StatementSome obese individuals maintain normal glycemic control. Despite being obese, these individuals have low risk for metabolic complications, including type-II diabetes. If we better understood why some obese people maintain normoglycemia then we might develop new approaches for treating metabolic complications associated with obesity. However, the causative factors underlying glycemic control in obesity remain unknown. We discovered that, despite persistence of the obese state, SM/J mice enter into diabetic remission: returning to normoglycemia and reestablishing glucose tolerance and improving insulin sensitivity. A prominent phenotype is that they dramatically expand their brown adipose depots as they resolve glycemic dysfunction. Understanding this phenomenon in mice will open the door for innovative therapies aimed at improving glycemic control in obesity.
High Resolution Genome Wide Expression Analysis of Single Myofibers Using SMART-Seq
Authors: Blackburn Darren M. , Lazure Felicia , Corchado Aldo H. , Perkins Theodore J. , Najafabadi Hamed S. , Soleimani Vahab D. 
Published: August 2019

ABSTRACTSkeletal muscle is a heterogeneous tissue. Individual myofibers that make up muscle tissue exhibit variation in their metabolic and contractile properties. Although there are biochemical and histological assays to study myofiber heterogeneity, efficient methods to analyze the whole transcriptome of individual myofibers are lacking. We have developed single myofiber RNA-Seq (smfRNA-Seq) to analyze the whole transcriptome of individual myofibers by combining single fiber isolation with Switching Mechanisms at 5’ end of RNA Template (SMART) technology. Our method provides high-resolution genome wide expression profiles of single myofibers. Using smfRNA-Seq, we have analyzed the differences in the transcriptome of young and old myofibers to validate the effectiveness of this new method. Using smfRNA-Seq, we performed comparative gene expression analysis between single myofibers from young and old mice. Our data suggests that aging leads to significant changes in the expression of metabolic and structural genes in myofibers. Our data suggests that smfRNA-Seq is a powerful tool to study developmental, disease and age-related dynamics in the composition of skeletal muscle.