bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with the Development of Posterior Capsule Opacification Requiring Yttrium Aluminum Garnet Capsulotomy
Authors: Tokko Hassan A. , Hussain Farhan , Al-Awadi Ahmad , Mei Frank , Zeiter John H. , Kim Chaesik , Tannir Justin R. , Shukairy Aman , Juzych Mark S. , McDermott Mark L. , Nassiri Nariman , Hughes Bret A.
Published: July 2019

SIGNIFICANCE

Determining risk factors for posterior capsule opacification will allow for further interventions to reduce the risk of development and thus additional procedures.

PURPOSE

The purpose of this study was to investigate risk factors associated with development of clinically significant posterior capsule opacification requiring yttrium aluminum garnet (YAG) capsulotomy.

METHODS

Medical records of patients (≥18 years) who underwent cataract surgery between January 1, 2011, and March 31, 2014, at Kresge Eye Institute were reviewed. Three hundred eyes requiring YAG capsulotomy up to 3 years after cataract surgery were included in the YAG capsulotomy group. Three hundred eyes not requiring YAG capsulotomy up to 3 years after cataract surgery were selected via age-matched simple randomization (control group).

RESULTS

The YAG capsulotomy group included patients with younger age (65.8 ± 11.3 vs. 70.1 ± 10.6 years,P< .001), more men (42.67 vs. 34.67%,P= .04), fewer patients with hypertension (73.00 vs. 83.00%,P< .001), and more patients with hydrophilic intraocular lenses (74.67 vs. 47.00%,P< .001). Logistic regression analysis demonstrated a negative association between YAG capsulotomy and age (coefficient, −0.04; 95% confidence interval [CI], 0.95 to 0.98;P< .001) and hydrophobic intraocular lenses (coefficient, −1.50; 95% CI, 0.15 to 0.33;P< .001), and a positive association with presence of glaucoma (coefficient, 0.88; 95% CI, 1.39 to 4.17;P= .002). Elapsed time to YAG capsulotomy was sooner in patients with a history of uveitis (95% CI, 5.10 to 9.70 months;P= .02) and insertion of hydrophilic intraocular lenses (95% CI, 18.67 to 21.57 months;P< .001).

CONCLUSIONS

Results of this study suggest that development of visually significant posterior capsule opacification is associated with younger age, glaucoma, and hydrophilic intraocular lenses, and it occurs earlier among those with hydrophilic intraocular lenses and a history of uveitis.
Conjunctival Redness Response to Corneal Stimulation
Authors: Alabi Emmanuel B. , Simpson Trefford L.
Published: July 2019

SIGNIFICANCE

The conjunctiva is an integral component of the ocular surface, and its vasculature forms a terminal vascular bed of the human internal carotid artery. No research on the response of conjunctival vasculature to ocular surface stimulation exists; however, it is essential to understand the local physiological and pathological responses to such a stimulus.

PURPOSE

The purpose of this study was to characterize the ocular redness levels in healthy participants after the application of noxious corneal stimulation.

METHODS

A computerized Belmonte pneumatic esthesiometer was used to determine detection thresholds (using ascending method of limits) and to randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each suprathreshold stimulus, a spectrophotometer was used to measure ipsilateral and contralateral conjunctival redness before and after delivery of the corneal stimulus. Redness between the stimulated and unstimulated eyes was analyzed using dependent t tests. The effects of stimulus intensity and modality on conjunctival redness were analyzed using repeated-measures analysis of variance (ANOVA). Tukey honestly significant difference tests were used for all post hoc analyses. P ≤ .05 was considered statistically significant.

RESULTS

In mechanical and chemical stimulation experiments, the stimulated eye became redder than the unstimulated eye (all t tests, P > .05). On average, redness increased from baseline as the corneal stimulus intensity increased with corneal stimulation (ANOVA, P < .05). Chemical stimulation produced greater conjunctival redness than did mechanical stimulation at all stimulation levels (ANOVA, P < .05; all Tukey honestly significant difference tests, P < .05).

CONCLUSIONS

Stimulation of the central cornea by noxious mechanical and chemical stimuli evokes a dose-dependent autonomic conjunctival redness response. Chemical stimulation of the cornea seems to evoke a greater response compared with mechanical stimulation. This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive ocular surface stimuli to autonomic responses.
Effects of Different Body Postures on the Intraocular Pressure in Patients with Primary Angle-Closure Disease
Authors: Park Ji-Hye , Yoo Chungkwon , Yang Kyung-Sook , Kim Yong Yeon
Published: July 2019

SIGNIFICANCE

Eyes with primary angle-closure disease showed higher intraocular pressure (IOP) in the recumbent postures including supine and lateral decubitus (LD) positions compared with the sitting position.

PURPOSE

The purpose of this study was to investigate the effects of different body postures on the IOP in eyes with primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG).

METHODS

This is a comparative case series of 31 patients with bilateral PAC disease, such as PACS, PAC, and PACG. The IOP was measured using Tonopen AVIA in sitting, supine, and right or left LD positions. Patients were instructed to rest their heads on the pillows in supine and LD positions. The eye on the lower side in the LD position was called dependent eye. The main outcome was the difference in IOP among different body postures.

RESULTS

Among the 62 eyes (31 patients), PACG, PAC, and PACS were noted in 44, 12, and 6 eyes, respectively. The IOP was not significantly different between the two eyes in sitting and supine positions, whereas the IOP was significantly higher in the dependent eye than in the nondependent eye in LD positions. Compared with that measured in the supine position, IOP differences of the dependent eye were higher than those of the nondependent eye when measured in LD position (right LD vs. supine, P = .02; left LD vs. supine, P = .01). In addition, when the study patients were divided into three groups according to their diagnosis, no significant differences were observed in the IOPs and IOP differences among the three groups.

CONCLUSIONS

Posture-induced IOP changes were comparable among eyes with PACS, PAC, and PACG.
“The Scalpel is Passed,” a Conversation With Dr Vincent J.M. DiMaio
Authors: Dana Suzanna
Published: July 2019

Editor's Note

This is the first article in a new series of interviews with mentors in forensic pathology. These interviews will also be recorded, and the audio files will be available online through the journal's Web site, http://links.lww.com/FMP/A31.
Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department
Authors: Guthrie Anne Marie , Baum Regan A. , Carter Craig , Dugan Adam , Jones Landon , Tackett Trei , Bailey Abby M.
Published: July 2019

Objectives

Ketamine is a safe and widely used sedative and analgesic in the pediatric emergency department (ED). The use of intranasal (IN) ketamine in exchange for the administration of intravenous sedatives or analgesics for procedural sedation in pediatric patients is not commonplace. The goal of this study was to evaluate provider perceptions and patient outcomes at varying doses of IN ketamine for anxiolysis, agitation, or analgesia.

Methods

From January 2018 to May 2018, we performed a prospective survey and chart review of pediatric patients receiving IN ketamine. The primary outcome was to determine provider satisfaction with using IN ketamine. Secondary objectives included comparing outcomes stratified by dose, adverse events, assessing for treatment failure, and ED length of stay (LOS). As a secondary comparison, patients receiving IN ketamine whom otherwise would have required procedural sedation with intravenous sedatives or analgesics were placed into a subgroup. This subgroup of patients was compared with a cohort who received intravenous sedatives or analgesics for procedural sedation during a similar period the preceding year (January 2017 to June 2017).

Results

Of the 196 cases, 100% of the providers were comfortable using IN ketamine. The median overall provider satisfaction was 90 out of 100, the perception of patient comfort was 75 out of 100, and perceived patient comfort was maximized when using doses between 3 and 5 mg/kg. There were 15 (7.7%) patients who experienced ketamine treatment failure. Overall, the rate of adverse events was 6%, but were considered minor [nausea (n = 3; 1.5%), dizziness (n = 2; 1%), and drowsiness (n = 2; 1%)]. No patients required respiratory support or intubation. The mean LOS was 237.9 minutes, compared with those who underwent procedural sedation with an LOS of 332.4 minutes (P < 0.001).

Conclusions

This study demonstrates that IN ketamine was able to provide safe and successful analgesia and anxiolysis in pediatric patients in an ED setting. In addition, providers expressed a high degree of satisfaction with using IN ketamine (90 out of 100) in addition to a high degree of patient comfort during the procedure (75 out of 100). Intranasal ketamine provides an alternative to intravenous medication normally requiring more resource-intensive monitoring. Procedural sedations are resource and time intensive activities that increase ED LOS. Intranasal ketamine used for anxiolysis and analgesia offers the benefits of freeing up resources of staff and monitoring while enhancing overall throughput through a pediatric ED.
A Systematic Review and Meta-Analysis of the Pressure-Induced Vasodilation Phenomenon and Its Role in the Pathophysiology of Ulcers
Authors: Zwanenburg Pieter R. , Backer Sophia F. M. , Obdeijn Miryam C. , Lapid Oren , Gans Sarah L. , Boermeester Marja A.
Published: July 2019

Background:

Physiologic studies show that tissue perfusion increases during moderate amounts of tissue compression. This is attributed to sensory nerves initiating a vasodilatory cascade referred to as pressure-induced vasodilation.

Methods:

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies investigating perfusion during pressure exposure longer than 10 minutes. Retrieved studies were assessed using the Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies. Results were pooled with random effects models. The body of evidence was rated using the Office of Health Assessment and Translation approach.

Results:

Twenty-nine articles were included, of which 19 articles were included in meta-analyses. The evidence indicates that moderate amounts of tissue compression have the capacity to increase perfusion in healthy humans by 46 percent (95 percent CI, 30 to 62 percent). Using the Office of Health Assessment and Translation approach, the authors found a high level of confidence in the body of evidence. Pressure-induced vasodilation blockade was associated with increased pressure ulcer formation. Pressure-induced vasodilation was impaired by neuropathy and by the drugs diclofenac and amiloride.

Conclusions:

This systematic review and meta-analysis indicates that healthy humans have the capacity to increase local perfusion in response to mechanical stress resulting from tissue compression. Because pressure-induced vasodilation is mediated by sensory nerves, pressure-induced vasodilation emphasizes the importance of sensory innervation for durable tissue integrity. Pressure-induced vasodilation impairment seems to provide a complementary explanation for the susceptibility of neuropathic tissues to pressure-induced lesions.
Medically Unexplained Symptoms and Antecedent Sexual Abuse: An Observational Study of a Birth Cohort
Authors: Duncan Roderick , Mulder Roger , Wilkinson Sam H. , Horwood John
Published: July 2019

Objective

Medically unexplained symptoms (MUS) are common and associated with high consumption of health care resources. Cross-sectional studies in selected and clinical populations show consistent linkages between history of childhood sexual abuse (CSA) and presentation with MUS and somatization. However, there are almost no well-controlled prospective studies in population samples.

Methods

Data were gathered in a longitudinal study of a New Zealand birth cohort born in 1977. Hospital e-record data for the period 2008–2015 (age, 30–38 years) were searched for a subsample of 408 study participants who were resident in one District Health Board region, and details of MUS contacts were recorded. Retrospective reports of CSA (<16 years) were obtained at ages 18 and 21 years. Associations between CSA and MUS were sequentially adjusted using logistic regression methods for both childhood confounders assessed before age 16 years and potential mediating mental health/family context up to age 30 years.

Results

Twenty (4.9%) participants were classified as having MUS, of whom 11 had a history of CSA. Severe CSA involving attempted/completed sexual penetration was strongly associated with risk of MUS (odds ratio = 11.6, 95% confidence interval = 4.3–31.7, p < .001). A substantial association remained after statistically adjusting for confounding and mediating mental health/family context (adjusted odds ratio = 5.1, 95% confidence interval = 1.2–21.3, p = .024). This strong association was specific to severe CSA (as opposed to childhood physical abuse) and to MUS rather than medically explained symptoms.

Conclusions

CSA involving attempted/completed penetration was strongly associated with attendance at secondary level care for MUS. Implications for prevention and treatment of MUS are discussed.
Social Role–Related Stress and Social Role–Related Reward as Related to Subsequent Subclinical Cardiovascular Disease in a Longitudinal Study of Midlife Women: The Study of Women's Health Across the Nation
Authors: Stewart Andrea Leigh , Barinas-Mitchell Emma , Matthews Karen A. , El Khoudary Samar R. , Magnani Jared W. , Jackson Elizabeth A. , Brooks Maria M.
Published: July 2019

Objective

The purpose of this study was to determine if midlife social role quality, defined by the stress and rewards associated with four social roles, is related to later-life subclinical cardiovascular disease (SCVD) in a cohort of women transitioning through menopause.

Methods

The Study of Women's Health Across the Nation (SWAN) is a longitudinal cohort study of midlife women. Stress and reward from four social roles (spouse, parent, employee, caregiver) were assessed at seven early visits. Later-life SCVD was assessed via carotid ultrasound and brachial-ankle pulse wave velocity at two later visits. We tested whether ever reporting an “extremely” or “quite a bit” stressful role was related to SCVD. We also tested whether cumulative stress and reward, as well as baseline and change in stress and reward were related to SCVD, adjusting for demographics and cardiovascular risk factors.

Results

Among 1602 women, reporting a stressful role during midlife (between ages 47 and 52 years) was associated with later-life (age 61 years) carotid intima-media thickness, which was 21 μm thicker than never reporting a stressful role. No significant relationships between stressful roles and other SCVD measures were identified. Cumulative and baseline change models of stress and reward were not related to SCVD.

Conclusion

A stressful social role in midlife was associated with greater atherosclerotic burden in later-life in a cohort of women transitioning through menopause. Social role rewards were unrelated to better later-life SCVD. These findings extend the knowledge of stress and cardiovascular disease in women by using measures of stress and reward for multiple social roles over the years of midlife.
A Novel Technique for Short Nose Correction in Asians: M-Shaped Conchal Cartilage Combining With Septal Extension Graft
Authors: An Yang , Feng Ning , Chen Lujia , Yang Xin , Yang Xiao , Xia Youchen , Xue Hongyu , Li Dong
Published: July 2019

Background:

Multiple techniques are available for short nose deformity correction. The septal extension graft represents the commonest method employed in Asians. However, a large number of surgeons hardly obtain esthetically satisfactory results since the majority of designs do not reflect the normally encountered surface anatomy of the nasal tip cartilage.

Objective:

The authors designed a novel technique, which combined the M-shaped conchal cartilage with the septal extension graft for overcoming the above shortcoming in Asians.

Methods:

Between February 2013 and March 2016, 33 patients presenting short nose deformity were surgically treated with the M-shaped conchal cartilage combined with the septal extension graft. The graft was an altered septal extension graft using the septal cartilage alongside the conchal cartilage. The harvested septal cartilage was located to the caudal septum and fixed with sutures. The conchal cartilage was trimmed into 2 strips, which were sutured together in an M-shape and firmly fixed in a bilateral manner to the caudal septal extension graft. Then, the alar cartilage was fixed with the M-shape graft. In all patients, nasal lengths, nasal tip projections, and nasolabial angles were assessed before and after surgery, respectively.

Results:

Nasal tip projections and nasal lengths showed remarkable increases, while columellar-labial angles were overtly decreased, in individuals surgically treated by the novel technique.

Conclusions:

This study presents a new method for correcting short nose deformity in Asians. The M-shaped conchal cartilage combined with the septal extension graft may effectively lengthen the nose while closely representing the actual surface of the esthetic nasal tip.
X-Linked IRAK1 Polymorphism is Associated with Sex-Related Differences in Polymorphonuclear Granulocyte and Monocyte Activation and Response Variabilities
Authors: Qin Yong , Peña Geber , Morcillo Patrick , Singh Sukhwinder , Mosenthal Anne C. , Livingston David H. , Spolarics Zoltan
Published: July 2019

Common X-linked genetic polymorphisms are expected to alter cellular responses affecting males and females differently through sex-linked inheritance pattern as well as X chromosome (ChrX) mosaicism and associated ChrX skewing, which is unique to females. We tested this hypothesis in ex vivo lipopolysaccharide and phorbol ester-stimulated polymorphonuclear granulocytes (PMNs) and monocytes from healthy volunteers (n = 51). Observations were analyzed after stratification by sex alone or the presence of variant IRAK1 haplotype a common X-linked polymorphism with previously demonstrated major clinical impacts. Upon cell activation, CD11b, CD45, CD66b, CD63, and CD14 expression was markedly and similarly elevated in healthy males and females. By contrast, PMN and monocyte activation measured by CD11b, CD66b, and CD63 was increased in variant-IRAK1 subjects as compared with WT. Stratification by IRAK1 genotype and sex showed similar cell activation effect on variant-IRAK1 subjects and an intermediate degree of cell activation in heterozygous mosaic females. The increased membrane expression of these proteins in variant-IRAK1 subjects was associated with similar or increased intersubject but uniformly decreased intrasubject cell response variabilities as compared with WT. We also tested white blood cell ChrX skewing in the healthy cohort as well as in a sample of female trauma patients (n = 201). ChrX inactivation ratios were similar in IRAK1 WT, variant, and heterozygous healthy subjects. Trauma patients showed a trend of blunted ChrX skewing at admission in homozygous variant-IRAK1 and heterozygous mosaic-IRAK1 female subjects as compared with WT. Trauma-induced de novo ChrX skewing was also depressed in variant-IRAK1 and mosaic-IRAK1 female trauma patients as compared with WT. Our study indicates that augmented PMN and monocyte activation in variant-IRAK1 subjects is accompanied by decreased intrasubject cellular variability and blunted de novo ChrX skewing in response to trauma. A more pronounced cell activation of PMNs and monocytes accompanied by decreased response variabilities in variant-IRAK1 subjects may be a contributing mechanism affecting the course of sepsis and trauma and may also impact sex-based outcome differences due to its X-linked inheritance pattern and high prevalence.
The Prognostic Usefulness of the Lactate/Albumin Ratio for Predicting Clinical Outcomes in Out-of-Hospital Cardiac Arrest: a Prospective, Multicenter Observational Study (koCARC) Study
Authors: Kong Taeyoung , Chung Sung Phil , Lee Hye Sun , Kim Sinae , Lee Jihwan , Hwang Sung Oh , Shin Sang Do , Song Kyoung Jun , Cha Kyung Chul , You Je Sung
Published: July 2019

Background and Purpose:

We aimed to evaluate the lactate/albumin ratio (LAR) to identify its significance as a prognostic marker for favorable neurologic outcome and survival in patients with return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). Based on the LAR and multiple parameters, we developed new nomograms and externally validated the tools.

Methods:

We conducted an observational study using a prospective, multicenter registry of out-of-cardiac arrest resuscitation provided by the Korean Cardiac Arrest Research Consortium registry from October 2015 to June 2017.

Results:

A total of 524 patients were included in this study. An increased LAR was significantly associated with decreased favorable neurologic outcomes (odds ratio [OR] 0.787; 95% confidence interval [CI], 0.630–0.983; P = 0.035) and survival at discharge (OR 0.744; 95% CI, 0.638–0.867; P < 0.001). The areas under the curve (AUCs) for predicting neurologic outcome and survival to discharge using the LAR were 0.824 (P < 0.001) and 0.781 (P < 0.001), respectively. An LAR value of more than the optimal cutoff values of 2.82 and 3.62 could significantly improve prediction of decreased favorable neurologic outcome and survival to discharge, respectively. We constructed nomograms based on the multivariate logistic model. The model for predicting favorable neurologic outcomes and survival discharge had AUCs of 0.927 (P < 0.001) and 0.872 (P < 0.001), respectively.

Conclusion:

The prognostic performance of the LAR was superior to a single measurement of lactate for predicting favorable neurologic outcomes and survival to discharge after OHCA. The newly developed nomograms can provide rapid prediction of probability of clinical outcomes.
Window of Opportunity to Mitigate Trauma-induced Coagulopathy
Authors: Leeper Christine M. , Strotmeyer Stephen J. , Neal Matthew D. , Gaines Barbara A.
Published: July 2019

Objective:

The aim of this study was to delineate the kinetics of coagulation dysregulation after injury in children.

Summary Background Data:

Trauma-induced coagulopathy is common and portends poor outcomes in severely-injured children. Transfer to pediatric trauma centers is common; time from injury to laboratory testing is therefore highly variable.

Methods:

Records of severely injured children age <18 years with rapid thromboelastography (TEG) on arrival and documented time of injury were queried. Standard definitions of hyperfibrinolysis (LY30 ≥3), fibrinolysis shutdown (SD; LY30 ≤0.8), and physiologic (LY30 = 0.9–2.9) were applied. Abbreviated Injury Scale score ≥3 defined severe traumatic brain injury (TBI). Variables of interest included demographics, injury mechanism, medications, mortality, and functional disability. Wilcoxon rank-sum and Kruskal-Wallis testing were utilized for skewed continuous data, and Chi-square or Fisher exact test was used for categorical data. To determine independent predictors of SD, multivariable logistic regression modeling was performed using the time from injury variable as well as variables determined a priori to be clinically relevant contributors to the development of SD (TBI, injury mechanism, and age).

Results:

A total of 285 patients were included: median (interquartile range) age = 11 (6–15), injury severity score = 17 (10–25), 75% blunt mechanism, 32% severe TBI, 11% mortality, 28% functional disability. None received antifibrinolytics or blood products before TEG testing. Physiologic phenotype was predominant within 1 hour of injury (51%); beyond 1 hour, fibrinolysis SD was the predominant phenotype (1–3 hours = 46%, >3 hours = 59%). Patients with TBI had significant increase in incidence of fibrinolysis SD beyond 1 hour after injury as compared to non-TBI patients. Physiologic fibrinolysis was associated with survival at all timepoints (P = 0.005).

Conclusions:

Fibrinolysis SD is a reactive, compensatory mechanism that is evident soon after injury. There appears to be an early and brief window of opportunity for intervention to mitigate the progression to TIC. Further studies should focus on understanding the dynamic events occurring immediately after injury to identify specific targets for intervention.
Medicare Patient Referral Networks to Female Pelvic Medicine and Reconstructive Surgeons Across the United States
Authors: Muffly Tyler M. , Gonzalez Javier , Khorshid Arian , Hajagos Janos , Kropat Georg
Published: July 2019

Objective

The source of urogynecology patient referrals remains poorly understood. We used novel methods to identify referral networks to female pelvic medicine and reconstructive surgeons (FPMRS) and to determine factors associated with physician connections.

Methods

A retrospective analysis of Centers for Medicare and Medicaid Services data with physician sharing relationships spanning 180 days during 2015 was performed. All patients studied were Medicare beneficiaries. Provider patient-sharing networks were modeled using social network analytics. To visualize the resulting flow of patients from referring providers to FPMRS, we encoded the node and edge data and mapped the data to a map of the United States.

Results

We studied 206,568 Medicare beneficiaries who were seen by 618 different board-certified FPMRS. Internal medicine physicians followed by nurse practitioners referred the most patients to FPMRS. Over half of referrals were made locally, with patients traveling less than 5 miles from the referring provider to the female pelvic surgeon. The median number of incoming Medicare patient referrals per FPMRS provider was 15 (interquartile range, 12–20) over a 6-month period. The high modularity of the referral network indicates that most providers refer their patients to a few female pelvic surgeons.

Conclusions

Medicare patient referrals to FPMRS are primarily and proportionally the highest from local internal medicine physicians.
Palliative Care in trauma: Not just for the dying
Authors: Fiorentino Michele , Hwang Franchesca , Pentakota Sri Ram , Livingston David H. , Mosenthal Anne C.
Published: July 2019

BACKGROUND

Palliative Care (PC) is indicated in patients with functional dependency and advanced care needs in addition to those with life-threatening conditions. Older trauma patients have PC needs due to increased risk of mortality and poor long-term outcomes. We hypothesized that older trauma patients discharged alive with poor outcomes are not easily identified nor receive PC interventions.

METHODS

Prospective observational study of trauma patients 55 years or older. Patients with poor functional outcomes defined by discharge Glasgow Outcome Scale Extended (GOSE) 1–4 or death at 6-month follow-up were analyzed for rate and timing of PC interventions including goals of care conversation (GOCC), do-not-resuscitate (DNR) order, do not intubate (DNI) order, and withdrawal of life supporting measures. Logistic regression was performed for having and timing of GOCC.

RESULTS

Three hundred fifteen (54%) of 585 patients had poor outcomes. Of patients who died, 94% had GOCC compared with 31% of patients who were discharged with GOSE 3 or 4. In patients who died, 85% had DNR order, 18% had DNI order, and 56% had withdrawal of ventilator. Only 24% and 9% of patients with GOSE of 3 or 4, respectively, had DNR orders. Fifty percent of the patients who were dead at 6-month follow-up had GOCC during initial hospitalization. The median time to DNR in patients that died was 2 days compared with 5 days and 1 day in GOSE 3 and 4 (p = 0.046). Age, injury severity scale, and preexisting limited physiological reserve were predictive of having a GOCC.

CONCLUSION

The PC utilization was very high for older trauma patients who died in hospital. In contrast, the majority of those who were discharged alive, but with poor outcomes, did not have PC. Development of triggers to identify older trauma patients, who would benefit from PC, could close this gap and improve quality of care and outcomes.
Coordination of Tissue Cell Polarity by Auxin Transport and Signaling
Authors: Verna Carla , Ravichandran Sree Janani , Sawchuk Megan G. , Linh Nguyen Manh , Scarpella Enrico
Published: July 2019

Coordination of polarity between cells in tissues is key to multicellular organism development. In animals, coordination of this tissue cell polarity often requires direct cell-cell interactions and cell movements, which are precluded in plants by a wall that separates cells and holds them in place; yet plants coordinate the polarity of hundreds of cells during the formation of the veins in their leaves. Overwhelming experimental evidence suggests that the plant signaling molecule auxin coordinates tissue cell polarity to induce vein formation, but how auxin does so is unclear. The prevailing hypothesis proposes that GNOM, a regulator of vesicle formation during protein trafficking, positions auxin transporters of the PIN-FORMED family to the correct side of the plasma membrane. The resulting cell-to-cell, polar transport of auxin would coordinate tissue cell polarity and would induce vein formation. Here we tested this hypothesis by means of a combination of cellular imaging, molecular genetic analysis, and chemical induction and inhibition. Contrary to predictions of the hypothesis, we find that auxin-induced vein formation occurs in the absence of PIN-FORMED proteins or any known intercellular auxin transporter, that the residual auxin-transport-independent vein-patterning activity relies on auxin signaling, and that aGNOM-dependent signal that coordinates tissue cell polarity to induce vein formation acts upstream of both auxin transport and signaling. Our results reveal synergism between auxin transport and signaling, and their unsuspected control byGNOM, in the coordination of tissue cell polarity during vein patterning, one of the most spectacular and informative expressions of tissue cell polarization in plants.
Scale free topology as an effective feedback system
Authors: Rivkind Alexander , Schreier Hallel , Brenner Naama , Barak Omri
Published: July 2019

Biological networks are often heterogeneous in their connectivity pattern, with degree distributions featuring a heavy tail of highly connected hubs. The implications of this heterogeneity on dynamical properties are a topic of much interest. Here we introduce a novel approach to analyze such networks the lumped hub approximation. Based on the observation that in finite networks a small number of hubs have a disproportionate effect on the entire system, we construct an approximation by lumping these nodes into a single effective hub, and replacing the rest by a homogeneous bulk. We use this approximation to study dynamics of networks with scale-free degree distributions, focusing on their probability of convergence to fixed points. We find that the approximation preserves convergence statistics over a wide range of settings. Our mapping provides a parametrization of scale free topology which is predictive at the ensemble level and also retains properties of individual realizations. Specifically for outgoing scale-free distributions, the role of the effective hub on the network can be elucidated by feedback analysis. We show that outgoing hubs have an organizing role that can drive the network to convergence, in analogy to suppression of chaos by an external drive. In contrast, incoming hubs have no such property, resulting in a marked difference between the behavior of networks with outgoing vs. incoming scale free degree distribution. Combining feedback analysis with mean field theory predicts a transition between convergent and divergent dynamics which is corroborated by numerical simulations. Our results show how interpreting topology as a feedback circuit can provide novel insights on dynamics. Furthermore, we highlight the effect of a handful of outlying hubs, rather than of the connectivity distribution law as a whole, on network dynamics.
Clonal transmission and new mechanism of resistance to trimethoprim-sulfamethoxazole in Stenotrophomonas maltophilia strains isolated in a neonatology unit at Antananarivo, Madagascar, deciphered by whole genome sequence analysis
Authors: Noah Rabenandrasana Mamitina Alain , Andrianoelina Volasoa , Bonneault Melanie , Herindrainy Perlinot , Garin Benoit , Breurec Sebastien , Delarocque-Astagneau Elisabeth , Andrianirina Zafitsara Zo , Enouf Vincent , Huynh Bich-Tram , Opatowski Lulla , Collard Jean-Marc
Published: July 2019

Stenotrophomonas maltophilia has been recognized as an emerging multidrug resistant organism in hospital settings due to its resistance to a broad range of antimicrobial agents. These include β-lactams and aminoglycosides, afforded by the existence of intrinsic and acquired resistance mechanisms. Trimethoprim/sulfamethoxazole (SXT) is recommended as one of the best treatment choices against S. maltophilia infections; however increasing resistance to SXT has complicated the treatment. From July 2014 to March 2015, individuals and surfaces from a neonatology ward in Antananarivo, Madagascar, were longitudinally followed to assess the transmission of bacteria resistant to antibiotics between neonates, individuals (parents and nurses) and ward environments. Four S. maltophilia strains were successively isolated from a water-tap (N=1), from feces obtained from a newborn (N=1), and nursing staff (N=2). Antimicrobial susceptibility testing and whole genome sequencing were performed on each isolate. Based on coregenome alignment, all strains were identical and belonged to the new sequence type ST-288. They were resistant to trimethoprim-sulfamethoxazole, carbapenems and intermediate to levofloxacin. Each isolate carried the aadB, strA, strB and sul1 genes located in a class I integron but variants of the dfrA gene were absent. We assessed by PROVEAN analysis the single nucleotide mutations found in folA, folC and folM genes and only the mutation in folA (A114T:GCC→ACC) has an effect on the activity of trimethoprim. Our findings demonstrated the prolonged presence of SXT-resistant S. maltophilia in a clinical setting with consecutive transfers from the environment to a newborn and staff based on the isolation dates. We also hypothesized that single nucleotide mutations in folA could be responsible for trimethoprim resistance.
Transfer of CRISPR-like activity of MIMIVIRE into Bacteria
Authors: Said Azza , Bernard La Scola , Anthony Levasseur , Pierre Perrin , Eric Chabrière , Didier Raoult
Published: July 2019

MIMIVIRE is a defence system utilized by lineage A Mimiviruses against Zamilon virophages. It is composed of a helicase, a nuclease and a gene of unknown function here named trcg (for Target Repeat-Containing gene), which contains four 15-bp repeats identical to the Zamilon sequence. Their silencing restored susceptibility to Zamilon, and the CRISPR-Cas4-like activity of the nuclease was recently characterised. We expressed these 3 genes after transformation of a modified strain of Escherichia coli made resistant to ampicillin, chloramphenicol and tetracycline. The virophage repeats were replaced with four repeats of 15 nucleotides identical to a sequence in the tetracycline resistance gene. The induction of the MIMIVIRE genes restored E. coli sensitivity to tetracycline; the tetracycline operon and its supporting plasmid harbouring the chloramphenicol resistance gene vanished. We therefore efficiently transferred the defence system MIMIVIRE from giant Mimivirus against virophage to E. coli to clear it from a plasmid.
Deciphering the functioning of microbial communities: shedding light on the critical steps in metaproteomics
Authors: Géron Augustin , Werner Johannes , Wattiez Ruddy , Lebaron Philippe , Matallana-Surget Sabine
Published: July 2019

Unraveling the complex structure and functioning of microbial communities is essential to accurately predict the impact of perturbations and/or environmental changes. From all molecular tools available today to resolve the dynamics of microbial communities, metaproteomics stands out, allowing the establishment of phenotype-genotype linkages. Despite its rapid development, this technology has faced many technical challenges that still hamper its potential power. How to maximize the number of protein identification, improve quality of protein annotation and provide reliable ecological interpretation, are questions of immediate urgency. In our study, we used a robust metaproteomic workflow combining two protein fractionation approaches (gel-basedversusgel-free) and four protein search databases derived from the same metagenome to analyze the same seawater sample. The resulting eight metaproteomes provided different outcomes in terms of (i) total protein numbers, (ii) taxonomic structures, and (iii) protein functions. The characterization and/or representativeness of numerous proteins from ecologically relevant taxa such asPelagibacterales,RhodobacteralesandSynechococcales, as well as crucial environmental processes, such as nutrient uptake, nitrogen assimilation, light harvesting and oxidative stress response were found to be particularly affected by the methodology. Our results provide clear evidences that the use of different protein search databases significantly alters the biological conclusions in both gel-free and gel-based approaches. Our findings emphasize the importance of diversifying the experimental workflow for a comprehensive metaproteomic study.
Differential attention-dependent adjustment of frequency, power and phase in primary sensory and frontoparietal areas
Authors: Suess Nina , Hartmann Thomas , Weisz Nathan
Published: July 2019

Continuously prioritizing behaviourally relevant information from the environment for improved stimulus processing is a crucial function of attention. Low-frequency phase alignment of neural activity in primary sensory areas, with respect to attended/ignored features has been suggested to support top-down prioritization. Phase adjustment in frontoparietal regions has not been widely studied, despite general implication of these in top-down selection of information. In the current MEG study, we investigated how ongoing oscillatory activity of both sensory and non-sensory brain regions are differentially impacted by attentional focus. Participants performed an established intermodal selective attention task, where low-frequency auditory (1.6 Hz) and visual (1.8 Hz) stimuli were presented simultaneously. We instructed participants to either attend to the auditory or to the visual stimuli and to detect targets while ignoring the other stimulus stream. As expected, the strongest phase adjustment was observed in primary sensory regions for auditory and for visual stimulation, independent of attentional focus. We found greater differences in phase locking between attended and ignored stimulation for the visual modality. Interestingly, auditory temporal regions show small but significant attention-dependent entrainment even for visual stimulation. Extending findings from invasive recordings in non-human primates, we demonstrate an effect of attentional focus on the phase of the entrained oscillations in auditory and visual cortex which may be driven by phase locked increases of induced power. In contrast to the effects in sensory areas, attentional focus adjusted the peak frequencies in nonsensory areas. Spatially these areas show a striking overlap with core regions of the dorsal attention network and the frontoparietal network. This suggests that these areas prioritize the attended modality by optimally exploiting the temporal structure of stimulation. Overall, our study complements and extends previous work by showing a differential effect of attentional focus on entrained oscillations in primary sensory areas and frontoparietal areas.
Finding and extending ancient simple sequence repeat-derived regions in the human genome
Authors: Shortt Jonathan A. , Ruggiero Robert P. , Cox Corey , Wacholder Aaron C. , Pollock David D.
Published: July 2019

Background

Previously, 3% of the human genome has been annotated as simple sequence repeats (SSRs), similar to the proportion annotated as protein coding. The origin of much of the genome is not well annotated, however, and some of the unidentified regions are likely to be ancient SSR-derived regions not identified by current methods. The identification of these regions is complicated because SSRs appear to evolve through complex cycles of expansion and contraction, often interrupted by mutations that alter both the repeated motif and mutation rate. We applied an empirical, kmer-based, approach to identify genome regions that are likely derived from SSRs.

Results

The sequences flanking annotated SSRs are enriched for similar sequences and for SSRs with similar motifs, suggesting that the evolutionary remains of SSR activity abound in regions near obvious SSRs. Using our previously described P-clouds approach, we identified ‘SSR-clouds’, groups of similar kmers (or ‘oligos’) that are enriched near a training set of unbroken SSR loci, and then used the SSR-clouds to detect likely SSR-derived regions throughout the genome.

Conclusions

Our analysis indicates that the amount of likely SSR-derived sequence in the human genome is 6.77%, over twice as much as previous estimates, including millions of newly identified ancient SSR-derived loci. SSR-clouds identified poly-A sequences adjacent to transposable element termini in over 74% of the oldest class ofAlu(roughly,AluJ), validating the sensitivity of the approach. Poly-A’s annotated by SSR-clouds also had a length distribution that was more consistent with their poly-A origins, with mean about 35 bp even in olderAlus. This work demonstrate that the high sensitivity provided by SSR-Clouds improves the detection of SSR-derived regions and will enable deeper analysis of how decaying repeats contribute to genome structure.
Discovery of powdery mildew resistance gene candidates fromAegilops biuncialischromosome 2Mbbased on transcriptome sequencing
Authors: Li Huanhuan , Dong Zhenjie , Ma Chao , Tian Xiubin , Xiang Zhiguo , Xia Qing , Ma Pengtao , Liu Wenxuan
Published: July 2019

Powdery mildew is one of the most widespread diseases of wheat. Breeding resistant varieties by utilization of resistance genes is considered as the most economic and effective method of controlling this disease. Previous study showed that the gene(s) at 2Mbin Chinese Spring (CS)-Aegilops biuncialis2Mbdisomic addition line TA7733 conferred high resistance to powdery mildew. In this study, 15Bgtisolates prevalent in different regions of China were used to further test the resistance spectrum of TA7733. As a result, TA7733 was high resistance to all tested isolates, indicating that the gene(s) on chromosome 2Mbwas broad-spectrum powdery mildew resistance. In order to mine resistance gene candidates and develop 2Mb-specific molecular markers to assist the transfer resistance gene(s) at chromosome 2Mb, RNA-seq of TA7733 and CS was conducted before and afterBgt-infection, generating a total of 158,953 unigenes. Of which, 7,278 unigenes were TA7733-specific which were not expressed in CS, and 295 out of these 7,278 unigenes were annotated as R genes. Based on Blastn against with CS Ref Seq v1.0, 61 R genes were further mapped to homoeologous group 2. Analysis of R gene-specific molecular markers designed from R gene sequences verified 40 out of 61 R genes to be 2Mbspecific. Annotation of these 40 R genes showed most genes encoded nucleotide binding leucine rich repeat (NLR) protein, being most likely resistance gene candidates. The broad-spectrum powdery mildew resistance gene(s), disease resistance gene candidates, and functional molecular markers of 2Mb-specific in present study will not only lay foundations for transferring disease resistance gene(s) from 2Mbto common wheat by inducing CS-Ae. biuncialishomoeologous recombination, but also provide useful candidates for isolating and cloning resistance gene(s) and dissecting molecular and genetic mechanisms of disease resistance from 2Mb.
The mammalian plasma membrane is defined by transmembrane asymmetries in lipid unsaturation, leaflet packing, and protein shape
Authors: Lorent JH , Levental KR , Ganesan L , Rivera-Longsworth G , Sezgin E. , Doktorova MD , Lyman E , Levental I
Published: July 2019

A fundamental feature of cellular plasma membranes (PM) is asymmetric lipid distribution between the bilayer leaflets. However, neither the detailed, comprehensive compositions of individual PM leaflets, nor how these contribute to structural membrane asymmetries have been defined. We report the distinct lipidomes and biophysical properties of both monolayers in living mammalian PMs. Phospholipid unsaturation is dramatically asymmetric, with the cytoplasmic leaflet being ∼2-fold more unsaturated than the exoplasmic. Atomistic simulations and spectroscopy of leaflet-selective fluorescent probes reveal that the outer PM leaflet is more packed and less diffusive than the inner leaflet, with this biophysical asymmetry maintained in the endocytic system. The structural asymmetry of the PM is reflected in asymmetric structures of protein transmembrane domains (TMD). These structural asymmetries are conserved throughout Eukaryota, suggesting fundamental cellular design principles.
Regulation of nuclear-cytoplasmic partitioning by thelin-28-lin-46pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression inC. elegans
Authors: Ilbay Orkan , Ambros Victor
Published: July 2019

MicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. InC. elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2) stage cell-fate, and thelet-7-family microRNAs temporally down-regulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel tolet-7-family microRNAs, the conserved RNA binding protein LIN-28 and its downstream genelin-46, also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how thelin-28-lin-46pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by thelin-28-lin-46pathway is independent of thelet-7/lin-4microRNA complementary sites (LCSs) in thehbl-13’UTR, and involves a stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that the robust progression from L2 to L3 cell-fates depends on the combination of two distinct modes of HBL-1 down-regulation: decreased synthesis of HBL-1 vialet-7-family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of thelin-28-lin-46pathway. Like HBL-1, many microRNA targets are transcription factors (TFs); and cooperation between regulation of nuclear accumulation and microRNA-mediated control of synthesis rate may be required to increase the precision of or confer robustness to down-regulation of these microRNA target TFs, which can be critical to achieve the optimal phenotypes.