bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Microbial Populations on the Creeping Bentgrass Phyllosphere to Periodic Fungicide Applications
Authors: Doherty Joseph R. , Botti-Marino Megan , Kerns James P. , Ritchie David F. , Roberts Joseph A.
Published: May 2017

Fungicides are frequently applied on golf course putting greens to combat the myriad of diseases that can affect them; however, it is unknown how these fungicides may affect microbial populations. Plant-associated microbial communities are intimately involved with plant development and soil biological processes. This two-year study was designed to evaluate the impact of five selected fungicides on culturable actinomycetes, fungi, general bacteria, and fluorescent pseudomonads residing in the turfgrass phyllosphere. Fungicides were applied at label rates on a 14-day interval. Four samples, consisting of five individual turf plants, were taken five days post-application. Samples were homogenized in 1 ml sterile deionized water and serial diluted to 10−3 and 10−5. Each dilution was then plated onto four different media (actinomycete isolation agar, acidified potato dextrose agar, nutrient agar + 1% sucrose, and King’s B) for enumeration of microbial populations. Fungicides had both positive and negative impacts on the culturable microbes tested, although population shifts across all treatments were observed with the prevailing weather conditions. These results show that while response to repeated fungicide application appears to be organism dependent, microbes are not completely removed from the environment.
Core Competencies or a Competent Core? A Scoping Review and Realist Synthesis of Invasive Bedside Procedural Skills Training in Internal Medicine
Authors: Brydges Ryan , Stroud Lynfa , Wong Brian M. , Holmboe Eric S. , Imrie Kevin , Hatala Rose
Published: May 2017

Purpose

Invasive bedside procedures are core competencies for internal medicine, yet no formal training guidelines exist. The authors conducted a scoping review and realist synthesis to characterize current training for lumbar puncture, arthrocentesis, paracentesis, thoracentesis, and central venous catheterization. They aimed to collate how educators justify using specific interventions, establish which interventions have the best evidence, and offer directions for future research and training.

Method

The authors systematically searched Medline, Embase, the Cochrane Library, and ERIC through April 2015. Studies were screened in three phases; all reviews were performed independently and in duplicate. The authors extracted information on learner and patient demographics, study design and methodological quality, and details of training interventions and measured outcomes. A three-step realist synthesis was performed to synthesize findings on each study’s context, mechanism, and outcome, and to identify a foundational training model.

Results

From an initial 6,671 studies, 149 studies were further reduced to 67 (45%) reporting sufficient information for realist synthesis. Analysis yielded four types of procedural skills training interventions. There was relative consistency across contexts and significant differences in mechanisms and outcomes across the four intervention types. The medical procedural service was identified as an adaptable foundational training model.

Conclusions

The observed heterogeneity in procedural skills training implies that programs are not consistently developing residents who are competent in core procedures. The findings suggest that researchers in education and quality improvement will need to collaborate to design training that develops a “competent core” of proceduralists using simulation and clinical rotations.
Radial Head Ingrowth Anatomic Implant Versus Smooth Stem Monoblock Implant in Acute Terrible Triad Injury: A Prospective Comparative Study
Authors: Rodriguez-Quintana David , Comulada David Beaton , Rodriguez-Quintana Natalie , Lopez-Gonzalez Francisco
Published: May 2017

Objective:

This study aimed to compare clinical outcomes and radiographic findings between patients who received 2 different implants (smooth-stemmed modular implant or an anatomic press-fit implant) on patients with acute terrible triad injuries.

Design:

Prospective cohort.

Setting:

Level II Trauma center, University hospital.

Patients/Participants:

Thirty-four patients with an isolated terrible triad injury were divided into 2 study groups (n = 17 each) with different sets of radial head implants and followed for 2 years. A total of 14 patients in each group (n = 28) completed the study.

Intervention:

Group 1 received a smooth-stemmed round modular monopolar implant. Group 2 received an in-growth modular monopolar press-fit anatomic implant.

Main Outcome Measurements:

Clinical outcomes were evaluated using the Visual Analog Scale, Mayo Index, and Disabilities of the Arm, Shoulder, and Hand (DASH) survey. Radiographs were evaluated for ectopic bone formation and loosening.

Results:

No difference in clinical outcome when comparing range of motion and functionally scores between groups. Ectopic bone formation occurred equally with implants. Bone formation at the proximal radius under the implant occurred more in group 1 (85.7%), (P = 0.046). Five press-fit stems had radiolucent lines at 2-year follow-up. Two were removed because of symptomatic loosening.

Conclusions:

Short-term outcomes for both implants showed to be equally effective treatment options. The in vitro biomechanical advantages of anatomic implants do not translate into short-term improved outcomes. Symptomatic aseptic loosening in anatomic implants is common. Bone formation at the proximal radial neck was observed more with smooth-stemmed implants; further studies should assess this findings and clinical implication.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
A Novel Computerized Test for Detecting and Monitoring Visual Attentional Deficits and Delirium in the ICU
Authors: Green Cameron , Hendry Kirsty , Wilson Elizabeth S. , Walsh Timothy , Allerhand Mike , MacLullich Alasdair M. J. , Tieges Zoë
Published: May 2017

Objectives:

Delirium in the ICU is associated with poor outcomes but is under-detected. Here we evaluated performance of a novel, graded test for objectively detecting inattention in delirium, implemented on a custom-built computerized device (Edinburgh Delirium Test Box–ICU).

Design:

A pilot study was conducted, followed by a prospective case-control study.

Setting:

Royal Infirmary of Edinburgh General ICU.

Patients:

A pilot study was conducted in an opportunistic sample of 20 patients. This was followed by a validation study in 30 selected patients with and without delirium (median age, 63 yr; range, 23–84) who were assessed with the Edinburgh Delirium Test Box–ICU on up to 5 separate days. Presence of delirium was assessed using the Confusion Assessment Method for the ICU.

Measurements and Main Results:

The Edinburgh Delirium Test Box–ICU involves a behavioral assessment and a computerized test of attention, requiring patients to count slowly presented lights. Thirty patients were assessed a total of 79 times (n = 31, 23, 15, 8, and 2 for subsequent assessments; 38% delirious). Edinburgh Delirium Test Box–ICU scores (range, 0–11) were lower for patients with delirium than those without at the first (median, 0 vs 9.5), second (median, 3.5 vs 9), and third (median, 0 vs 10.5) assessments (all p < 0.001). An Edinburgh Delirium Test Box–ICU score less than or equal to 5 was 100% sensitive and 92% specific to delirium across assessments. Longitudinally, participants’ Edinburgh Delirium Test Box–ICU performance was associated with delirium status.

Conclusions:

These findings suggest that the Edinburgh Delirium Test Box–ICU has diagnostic utility in detecting ICU delirium in patients with Richmond Agitation and Sedation Scale Score greater than –3. The Edinburgh Delirium Test Box–ICU has potential additional value in longitudinally tracking attentional deficits because it provides a range of scores and is sensitive to change.
PREDICTORS OF REFRACTORY MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION FOLLOWING INTRAVITREAL BEVACIZUMAB
Authors: Moon Byung Gil , Cho Ah Ran , Kim You Na , Kim June-Gone
Published: May 2017

Purpose:

To evaluate the predictors of refractory macular edema (ME) that develops despite multiple bevacizumab injections in patients with branch retinal vein occlusion (BRVO).

Methods:

A total of 107 patients who followed at least 2 years were assigned to 2 groups: a refractory group (n = 56) and a responsive group (n = 51). Baseline characteristics, treatment response at 3 months, and fluorescein angiographic findings at 6 months were compared. Then we tried to identify factors associated with refractory ME development.

Results:

Compared to the responsive group, the refractory group had older age, longer pre-treatment duration, and shorter occlusion distance from disk. At 3 months, the refractory group exhibited lower visual acuity, thicker central retinal thickness (CRT), and larger proportion of external limiting membrane (ELM) and outer plexiform layer disruption. After 6 months, proportion of unresolved vein occlusion, macular ischemia, number of microaneurysms, and non-perfusion areas were higher in the refractory group. Refractory ME was associated with pre-treatment duration ≥3 months, short occlusion distance from disk, thick CRT and ELM disruption at 3 months, and unresolved vein occlusion at 6 months.

Conclusion:

If BRVO-ME patients exhibit the above-mentioned characteristics, they may have refractory ME, which should inform treatment decisions.
DYSFUNCTIONAL AUTONOMIC REGULATION OF THE CHOROID IN CENTRAL SEROUS CHORIORETINOPATHY
Authors: Nathaniel Roybal C. , Sledz Elisabeth , Elshatory Yasser , Zhang Li , Almeida David R. P. , Chin Eric K. , Critser Brice , Abramoff Michael D. , Russell Stephen R.
Published: May 2017

Purpose:

To study the effect of changing perfusion pressures on retinal and choroidal structure in central serous chorioretinopathy (CSC).

Methods:

This prospective observational case series included seven healthy volunteers (14 eyes) and seven patients (14 eyes) with CSC. Each patient underwent spectral domain optical coherence tomography with enhanced depth imaging in the upright (sitting) and supine positions. Image segmentation focused on central macular thickness, subretinal fluid, total macular volume, choroidal thickness, and choriocapillaris thickness. Blood pressure and heart rate were measured in the upright and supine positions.

Results:

Choriocapillaris thickness was thicker in CSC participants (34.23 μm; range, 30.9–36.5 μm) compared with healthy controls (13.96 μm; range, 7.15–23.87 μm) (P ≤ 0.001). The choroid was similarly thicker in CSC participants (371.4 μm; range, 200.2–459.4 μm) compared with healthy controls (231.4 μm; range 161.8–287.5 μm) (P ≤ 0.001). Choroidal thickness increased in patients with CSC when transitioning from upright (371.4 μm) to supine (377.8 μm) (P ≤ 0.01). By contrast, there was an 11.97% decrease in choroid thickness in normal controls when transitioning from upright (231.4 μm) to supine (203.9 μm). There were no significant hemodynamic changes.

Conclusion:

We demonstrated that choroidal thickness increased in response to increased perfusion pressures in patients with CSC and not in normal controls. These findings likely represent an autonomic dysregulation of choroidal blood flow in patients with CSC.
CLASSIFICATION OF HALLER VESSEL ARRANGEMENTS IN ACUTE AND CHRONIC CENTRAL SEROUS CHORIORETINOPATHY IMAGED WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY
Authors: Savastano Maria C. , Dansingani Kunal K. , Rispoli Marco , Virgili Gianni , Savastano Alfonso , Freund K. Bailey , Lumbroso Bruno
Published: May 2017

Purpose:

To compare the prevailing patterns of Haller vessel arrangements at the posterior pole between healthy eyes and those with central serous chorioretinopathy (CSC) using en face optical coherence tomography.

Methods:

Eyes of normal subjects and patients with acute or chronic CSC underwent optical coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face sections at the level of the Haller layer were classified by two masked graders into five mutually exclusive morphologic categories (temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular). The relative prevalence of each Haller vessel arrangement pattern was determined for each phenotype.

Results:

Numbers of eyes examined were as follows: 154 eyes of 77 normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33 patients with chronic CSC. The mean age of participants was 44.4 ± 14.6 years for healthy subjects (M:F = 37:40), 48.5 ± 8.2 years (M:F = 24:7) for acute CSC, and 65.3 ± 13.1 years (M:F = 28:5) for chronic CSC. The relative prevalence of each Haller vessel arrangement pattern differed by phenotype. The temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas a reticular pattern was most prevalent in eyes with acute and/or chronic CSC (combined, 48.8%).

Conclusion:

A significant difference was observed in the prevalence of respective Haller vessel arrangement patterns between eyes of normal subjects and those of patients with either acute or chronic CSC. Although further study is needed to determine the mechanistic factors underlying these differences, and the hemodynamic implications, our data suggest that en face optical coherence tomography may find a formal role in choroidal disease classification.
Femtosecond Laser Assisted Pterygium Surgery
Authors: Fuest Matthias , Liu Yu-Chi , Coroneo Minas T. , Mehta Jodhbir S.
Published: May 2017

Purpose:

Pterygium is a prevalent ocular surface disorder. Conjunctival autografting (CAG) after pterygium resection is the gold standard treatment. Thinner CAGs without Tenon tissue provide better results but are technically difficult to achieve. We report on the first femtosecond laser (FSL)-assisted pterygium surgery (FLAPS) in humans.

Methods:

In a clinical trial, we treated 6 eyes of 5 patients with FLAPS. After manual removal of the pterygium, CAGs were dissected with the Ziemer Z8 at 60-μm depth and glued into the resection defect. CAG thickness and diameter were measured.

Results:

The CAG area measured 17.9% smaller than the laser settings (P = 0.03). Central (75.6 ± 13.7 μm) and peripheral (77.7 ± 13.2 μm) CAG thickness did not differ significantly (P = 0.3). No buttonholes or CAG tags occurred. The mean dissection time was 19.5 ± 1.2 seconds, and the time to remove the FSL-prepared CAG and to unfold it onto the cornea was 10.3 ± 3.8 seconds. During 35.8 ± 38.0 days of follow-up, no postoperative complication or recurrences occurred. The conjunctival epithelium had healed at the CAG resection site within 1 week with no evidence of scarring.

Conclusions:

FLAPS is a new technique, in which the preparation of an ultrathin CAG is done by the FSL. After optimization in porcine eyes, the clinical trial in the first 6 eyes was performed without any complications and the FSL might assist in further standardizing the surgical procedure. Longer follow-up and larger cohorts are needed to assess recurrence rates.
Bilateral Herpetic Keratitis After Bilateral Intravitreal Bevacizumab for Exudative Macular Degeneration
Authors: Derham Angeline M. , Chen Eric , Bunya Vatinee Y. , O'Malley Ronan E.
Published: May 2017

Purpose:

To report a case of bilateral herpetic epithelial keratitis after bilateral intravitreal bevacizumab injections for the treatment of exudative age-related macular degeneration.

Methods:

A 66-year-old man with diabetes and an extensive history of bilateral anti-vascular endothelial growth factor treatments for exudative age-related macular degeneration received an intravitreal bevacizumab injection in the right eye and triple therapy (bevacizumab, photodynamic therapy, and triamcinolone acetonide) in the left eye. After 4 days, he presented with pain, photophobia, tearing, and decreased vision in both eyes. Slit-lamp examination revealed bilateral dendritic epithelial lesions with terminal bulbs, and he was diagnosed with bilateral herpes simplex epithelial keratitis.

Results:

The patient was treated with ganciclovir ophthalmic ointment and oral acyclovir with resolution of signs and symptoms.

Conclusions:

To our knowledge, this is the first documented account of bilateral herpetic epithelial keratitis after bilateral intravitreal bevacizumab injections.
Own and partner pain intensity in older couples: longitudinal effects on depressive symptoms
Authors: Polenick Courtney A. , Brooks Jessica M. , Birditt Kira S.
Published: May 2017

Chronic pain has been linked to depression among individuals and their partners. Yet, little is known about long-term mutual influences between pain intensity and depressive symptoms within couples as they age. Using a nationally representative U.S. sample of wives and husbands aged 50 and older (mean = 64.53, SD = 7.86), this study explored the links between own and partner pain intensity and depressive symptoms across an 8-year period. A total of 963 heterosexual married couples drawn from the Health and Retirement Study completed interviews biennially from 2006 to 2014. Dyadic growth curve models examined mutual associations within couples and controlled for sociodemographic characteristics, length of marriage, and marital quality, along with self-rated health, number of chronic health conditions, and functional disability. For wives and husbands, their own greater baseline pain intensity was significantly linked to their own higher levels of depressive symptoms. Unexpectedly, wives with greater baseline pain intensity reported decreases in their depressive symptoms over time. There were also partner effects such that husbands' greater pain intensity at baseline was associated with increases in wives' depressive symptoms over time. Findings highlight the importance of considering both individual and spousal associations between pain intensity and depressive symptoms in later life. Understanding how individual and couple processes unfold may yield critical insights for the development of intervention and prevention efforts to maintain mental health among older chronic pain patients and their spouses.
Identifying Patient and Provider-specific Gaps in Care Among Patients With Hepatitis B
Authors: Kushner Tatyana , Lam Robert , Gray Daniel L. , Kaplan David E. , Serper Marina
Published: May 2017

Goals:

To examine patient, provider, and health system barriers to clinical follow-up among US veterans with chronic hepatitis B virus (HBV).

Background:

Studies have demonstrated deficiencies in clinical care and follow-up in HBV; however, patient, provider, and health-system barriers in non-Asian populations are understudied.

Study:

A retrospective cohort of 517 US veterans with chronic HBV at 3 diverse Veterans Affairs sites from 1999 to 2015. Laboratory testing and completion of clinical appointments were collected for 2 years following initial presentation.

Results:

Among HBV patients, 36% had drug abuse, 41% alcohol misuse, and 45% had psychiatric disorders. Patients had an average of 4.4 primary care visits within 2 years of the index hepatitis B surface antigen positive result, 38% had psychiatry visits, 21% had a psychiatric hospitalization; 26% saw gastroenterology/hepatology specialists. Within 1 year of the index hepatitis B surface antigen positive result, 75% had alanine aminotransferase testing, 14% had HBV entered into the problem list, and 8% had serologic confirmation. In multivariable analyses, cirrhosis [odds ratio (OR)=3.42; 95% confidence interval (CI), 1.84-6.36] was associated with higher odds of appropriate laboratory testing, alcohol misuse (OR=0.45; 95% CI, 0.29-0.80) was associated lower odds. Cirrhosis (OR=2.03; 95% CI, 1.11-3.72) and ≥2 primary care visits per year (OR=1.06; 95% CI, 1.01-1.11) were associated with higher odds of completing gastroenterology/hepatology consultation, whereas ≥1 psychiatric hospitalization in 2 years was associated with lower odds (OR=0.53; 95% CI, 0.34-0.82).

Conclusions:

In a diverse cohort of veterans with high psychiatric comorbidity and substance abuse, important patient and provider factors influence appropriate follow-up care. Future studies should evaluate the impact of provider education and care coordination strategies in HBV.
Seroprevalence of antibodies and antigens against hepatitis A–E viruses in refugees and asylum seekers in Germany in 2015
Authors: Jablonka Alexandra , Solbach Philipp , Wöbse Michael , Manns Michael P. , Schmidt Reinhold E. , Wedemeyer Heiner , Cornberg Markus , Behrens Georg M.N. , Hardtke Svenja
Published: May 2017

Background

Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies.

Methods

A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively.

Results

Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7–19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0–5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3).

Conclusion

The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.
HIV Infection Increases the Risk of Incident Psoriasis: A Nationwide Population-Based Cohort Study in Taiwan
Authors: Yen Yung-Feng , Jen I-An , Chen Marcelo , Lan Yu-Ching , Lee Chun-Yuan , Chuang Pei-Hung , Lee Yun , Arthur Chen Yi-Ming
Published: May 2017

Background:

HIV can cause an imbalance of T lymphocytes, which may contribute to the onset of psoriasis. However, the association of HIV with incident psoriasis has not been extensively studied.

Objectives:

The aim of this nationwide population-based cohort study was to determine the association of HIV with incident psoriasis.

Methods:

Since January 1, 2000, we identified adult people living with HIV/AIDS (PLWHA) from the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. All patients were followed until December 31, 2012, and observed for the occurrence of psoriasis. The time-dependent Cox proportional hazards model was used to determine the association of HIV with incident psoriasis, while considering death as a competing risk event.

Results:

Of the 102,070 patients (20,294 PLWHA and 81,776 matched controls), 248 (0.24%) had incident psoriasis during a mean follow-up period of 5.53 years, including 81 (0.40%) PLWHA and 171 (0.21%) controls. After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident psoriasis (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38 to 2.36).

Conclusions:

The population of PLWHA is living longer; clinicians need to be aware of their higher risk of psoriasis.
Active HCV Replication but Not HCV or CMV Seropositive Status Is Associated With Incident and Prevalent Type 2 Diabetes in Persons Living With HIV
Authors: De Luca Andrea , Lorenzini Patrizia , Castagna Antonella , Puoti Massimo , Gianotti Nicola , Castelli Francesco , Mastroianni Claudio , Maggiolo Franco , Antinori Andrea , Guaraldi Giovanni , Lichtner Miriam , d'Arminio Monforte Antonella ,   for the ICONA Foundation Study
Published: May 2017

Objective:

To analyze the association between chronic hepatitis C virus (HCV) and cytomegalovirus (CMV) infections with type 2 diabetes in HIV-infected patients.

Methods:

HIV-1-infected patients enrolled in ICONA, a prospective cohort study involving 42 tertiary care centers in Italy, were selected with the following characteristics: for the diabetes incidence analysis, all patients with available CMV IgG results (first available test = baseline) and without type 2 diabetes were followed until onset of type 2 diabetes, last available clinical follow-up, death or September 30, 2014, whichever occurred first; for the prevalence analysis, all ICONA patients were analyzed at their last follow-up visit. Main outcome measures were the new onset of type 2 diabetes (incidence analysis) and the prevalence of type 2 diabetes at last follow-up.

Results:

During 38,062 person-years of follow-up (PYFU) in 6505 individuals, we observed 140 cases of incident type 2 diabetes (Incidence rate 3.7, 95% CI: 3.1 to 4.3, per 1000 PYFU). In a multivariable Poisson regression model, HCV-antibody (Ab)+/HCV RNA+ patients [adjusted relative rate versus HCV-Ab negative 1.73 (95% CI: 1.08 to 2.78)] but not HCV Ab+RNA− or CMV IgG+ patients, had a higher risk of diabetes. Among 12,001 patients, 306 (2.5%) prevalent cases of type 2 diabetes were detected. HCV Ab+RNA+ status was independently associated with prevalent diabetes (adjusted Odds Ratio vs HCV Ab− 2.49; 95% CI: 1.08 to 5.74), whereas HCV-Ab+/HCV RNA− and CMV IgG+ status were not.

Conclusion:

In HIV-infected individuals, active HCV replication but not prior HCV exposure or latent CMV infection is associated with incident and prevalent type 2 diabetes.
Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock in Rats
Authors: Torres Filho Ivo P. , Torres Luciana N. , Salgado Christi , Dubick Michael A.
Published: May 2017

Introduction:

There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics.

Methods:

After baseline, 40% of total blood volume was removed from 44 anesthetized Sprague–Dawley male rats. One hour after hemorrhage, animals were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR, 15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled blood was used to quantify shed syndecan-1 in plasma; multiple systemic physiological parameters were recorded. In vivo glycocalyx thickness, microvascular permeability, and microhemodynamics were evaluated in >200 cremaster venules using intravital videomicroscopy.

Results:

Compared with baseline, resuscitation using adjuncts was associated with glycocalyx restoration of 97 ± 9% (ALM), 75 ± 8% (BHB/M), and 85 ± 5% (P-188): significantly higher than LR-only (56 ± 4%). Significantly better permeability, similar to SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels were measured after resuscitation with all adjuncts. Microhemodynamic changes were relatively small while systemic parameters such as mean arterial pressure and lactate improved but remained below or above the baseline, respectively, as expected from this hypotensive resuscitation model.

Conclusion:

The drugs ALM, BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive resuscitation in this HS model by mechanisms involving changes at the microvascular level including the glycocalyx.
Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms
Authors: Bellini C. , Bersi M. R. , Caulk A. W. , Ferruzzi J. , Milewicz D. M. , Ramirez F. , Rifkin D. B. , Tellides G. , Yanagisawa H. , Humphrey J. D.
Published: May 2017

Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wild-type controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.
Optimizing mating encounters by sexually dimorphic movements
Authors: Mizumoto Nobuaki , Abe Masato S. , Dobata Shigeto
Published: May 2017

All organisms with sexual reproduction undergo a process of mating, which essentially involves the encounter of two individuals belonging to different sexes. During mate search, both sexes should mutually optimize their encounters, thus raising a question of how they achieve this. Here, we show that a population with sexually dimorphic movement patterns achieves the highest individual mating success under a limited lifespan. Extensive simulations found and analytical approximations corroborated the existence of conditions under which sexual dimorphism in the movement patterns (i.e. how diffusively they move) is advantageous over sexual monomorphism. Mutual searchers with limited lifespans need to balance the speed and accuracy of finding their mates, and dimorphic movements can solve this trade-off. We further demonstrate that the sexual dimorphism can evolve from an initial sexually monomorphic population. Our results emphasize the importance of considering mutual optimization in problems of random search.
The evolution of lossy compression
Authors: Marzen Sarah E. , DeDeo Simon
Published: May 2017

In complex environments, there are costs to both ignorance and perception. An organism needs to track fitness-relevant information about its world, but the more information it tracks, the more resources it must devote to perception. As a first step towards a general understanding of this trade-off, we use a tool from information theory, rate–distortion theory, to study large, unstructured environments with fixed, randomly drawn penalties for stimuli confusion (‘distortions’). We identify two distinct regimes for organisms in these environments: a high-fidelity regime where perceptual costs grow linearly with environmental complexity, and a low-fidelity regime where perceptual costs are, remarkably, independent of the number of environmental states. This suggests that in environments of rapidly increasing complexity, well-adapted organisms will find themselves able to make, just barely, the most subtle distinctions in their environment.
Adhesion modulation using glue droplet spreading in spider capture silk
Authors: Amarpuri Gaurav , Zhang Ci , Blackledge Todd A. , Dhinojwala Ali
Published: May 2017

Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture spiral silk is composed of an axial fibre of flagelliform silk covered with glue droplets that are arranged in a beads-on-a-string morphology that allows multiple droplets to simultaneously extend and resist pull off. Previous studies showed that the adhesion of capture silk is responsive to environmental humidity, increasing up to an optimum humidity that varied among different spider species. The maximum adhesion was hypothesized to occur when the viscoelasticity of the glue optimized contributions from glue spreading and bulk cohesion. In this study, we show how glue droplet shape during peeling contributes significantly to capture silk adhesion. Both overspreading and underspreading of glue droplets reduces adhesion through changes in crack propagation and failure regime. Understanding the mechanism of stimuli-responsive adhesion of spider capture silk will lead to new designs for smarter adhesives.
Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15
Authors: Madsen Michael J , Knight Stacey , Sweeney Carol , Factor Rachel , Salama Mohamed , Rajamanickam Venkatesh , Welm Bryan E , Arunachalam Sasi , Jones Brandt , Rowe Kerry , Cessna Melissa , Thomas Alun , Kushi Lawrence H , Caan Bette J , Bernard Philip S , Camp Nicola J
Published: May 2017

It is well-known that breast tumors exhibit different expression patterns that can be used to assign intrinsic subtypes – the PAM50 assay, for example, categorizes tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like – yet tumors are often more complex than categorization can describe. We used 911 sporadic breast tumors to reparameterize expression from the PAM50 genes to five orthogonal tumor dimensions using principal components (PC). Three dimensions captured intrinsic subtype, two dimensions were novel, and all replicated in 945 TCGA tumors. By definition dimensions are independent, an important attribute for inclusion in downstream studies exploring effects of tumor diversity. One application where tumor subtyping has failed to provide impact is susceptibility genetics. Germline genetic heterogeneity reduces power for gene-finding. The identification of heritable tumor characteristics has potential to increase homogeneity. We compared 238 breast tumors from high-risk pedigrees not attributable toBRCA1orBRCA2to 911 sporadic breast tumors. Two PC dimensions were significantly enriched in the pedigrees (intrinsic subtypes were not). We performed proof-of-concept gene-mapping in one enriched pedigree and identified a 0.5 Mb genomewide significant region at 12q15 that segregated to the 8 breast cancer cases with the most extreme PC tumors through 32 meioses (p=2.6×10−8). In conclusion, our study: suggests a new approach to describe tumor diversity; supports the hypothesis that tumor characteristics are heritable providing new avenues for germline studies; and proposes a new breast cancer locus. Reparameterization of expression patterns may similarly inform other studies attempting to model the effects of tumor heterogeneity.
Mitochondrial pseudogenes suggest repeated inter-species hybridization among direct human ancestors
Authors: Popadin Konstantin , Gunbin Konstantin , Peshkin Leonid , Annis Sofia , Fleischmann Zoe , Kraytsberg Genya , Markuzon Natalya , Ackermann Rebecca R. , Khrapko Konstantin
Published: May 2017

The hypothesis that the evolution of humans involved hybridization between diverged species has been actively debated in recent years. We present novel evidence in support of this hypothesis: the analysis of nuclear pseudogenes of mtDNA (“NUMTs”). NUMTs are considered “mtDNA fossils”, as they preserve sequences of ancient mtDNA and thus carry unique information about ancestral populations. Our comparison of a NUMT sequence shared by humans, chimpanzees, and gorillas with their mtDNAs implies that, around the time of divergence between humans and chimpanzees, our evolutionary history involved the interbreeding of individuals whose mtDNA had diverged as much as ~4.5 Myr prior. This large divergence suggests a distant interspecies hybridization. Additionally, analysis of two other NUMTs suggests that such events occurred repeatedly. Our findings suggest a complex pattern of speciation in primate human ancestors and provide a potential explanation for the mosaic nature of fossil morphology found at the emergence of the hominin lineage.
High-risk Autism Spectrum Disorder Utah pedigrees: a novel Shared Genomic Segments analysis
Authors: Darlington Todd M , Bilder Deborah , Morgan Jubel , Jerominski Leslie , Rajamanickam Venkatesh , Sargent Rob , Camp Nicola J , Coon Hilary H
Published: May 2017

Progress in gene discovery for Autism Spectrum Disorder (ASD) has been rapid over the past decade, with major successes in validation of risk of predominantly rare, penetrant,de novoand inherited mutations in over 100 genes (de Rubies et al., 2015; Sanders et al., 2015). However, the majority of individuals with ASD diagnoses do not carry a rare, penetrant genetic risk factor. In fact, recent estimates suggest that most of the genetic liability of ASD is due to as yet undiscovered common, less penetrant inherited variation (Gaugler et al., 2014) which is much more difficult to detect. The study of extended, high-risk families adds significant information in our search for these common inherited risk factors. Here, we present results of a new, powerful pedigree analysis method (Shared Genomic Segments—SGS) on three large families from the Utah Autism Research Program. The method improves upon previous methods by allowing for within-family heterogeneity, and identifying exact region boundaries and subsets of cases who share for targeted follow-up analyses. Our SGS analyses identified one genome-wide significant shared segment on chromosome 17 (q21.32, p=1.47x10-8). Additional regions with suggestive evidence were identified on chromosomes 3, 4, 6, 8, 11, 13, 14, 15, and 18. Several of these segments showed evidence of sharing across families. Genes of interest in these regions includeATP8A1,DOCK3,CACNA2D2,ITGB3,AMBRA1,FOLH1,DGKZ,MTHFS,ARNT2,BTN2A2,BTN3A1,BTN3A3,BTN2A1, andBTN1A1. We are exploring multiple other lines of evidence to follow up these implicated regions and genes.
MutPred2: inferring the molecular and phenotypic impact of amino acid variants
Authors: Pejaver Vikas , Urresti Jorge , Lugo-Martinez Jose , Pagel Kymberleigh A. , Lin Guan Ning , Nam Hyun-Jun , Mort Matthew , Cooper David N. , Sebat Jonathan , Iakoucheva Lilia M. , Mooney Sean D. , Radivojac Predrag
Published: May 2017

We introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions, generates molecular mechanisms potentially causative of disease, and returns interpretable pathogenicity score distributions on individual genomes. While its prioritization performance is state-of-the-art, a novel and distinguishing feature of MutPred2 is the probabilistic modeling of variant impact on specific aspects of protein structure and function that can serve to guide experimental studies of phenotype-altering variants. We demonstrate the utility of MutPred2 in the identification of the structural and functional mutational signatures relevant to Mendelian disorders and the prioritization ofde novomutations associated with complex neurodevelopmental disorders. We then experimentally validate the functional impact of several variants identified in patients with such disorders. We argue that mechanism-driven studies of human inherited diseases have the potential to significantly accelerate the discovery of clinically actionable variants.

Availability:http://mutpred.mutdb.org/
Epigenome-wide association study of asthma and wheeze in childhood and adolescence
Authors: Arathimos Ryan , Suderman Matthew , Sharp Gemma C , Burrows Kimberley , Granell Raquel , Tilling Kate , Gaunt Tom R , Henderson John , Ring Susan , Richmond Rebecca , Relton Caroline L
Published: May 2017

Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis.

Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 years and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx. 1000 participants. We used Mendelian randomization (MR), a method of causal inference that uses genetic variants as instrumental variables, to infer the direction of association between DNA methylation and asthma.

We identified 302 CpGs associated with current asthma status (FDR-adjusted P-value <0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap between the two. Genes annotated to the 302 associated CpGs were enriched for pathways related to movement of cellular/subcellular components, locomotion, interleukin-4 production and eosinophil migration. All associations attenuated when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years, two sites were associated with current asthma after adjustment for cell counts. The CpGs mapped to theAP2A2andIL5RAgenes, with a -2.32 [95% CI -1.47,-3.18] and -2.49 [95% CI -1.56,-3.43] change in percentage methylation in asthma cases respectively. Two-sample bi-directional MR indicated a causal effect of asthma on DNA methylation at several CpG sites at 7.5 years. However, associations did not persist after adjustment for multiple testing. There was no evidence of a causal effect of asthma on DNA methylation at either of the two CpG sites at 16.5 years.

The majority of observed associations are driven by higher eosinophil cell counts in asthma cases, acting as an intermediate phenotype, with important implications for future studies of DNA methylation in atopic diseases.
A comparative study of endoderm differentiation in humans and chimpanzees
Authors: Blake Lauren E. , Thomas Samantha M. , Blischak John D. , Hsiao Chiaowen Joyce , Chavarria Claudia , Myrthil Marsha , Gilad Yoav , Pavlovic Bryan J.
Published: May 2017

There is substantial interest in the evolutionary forces that shaped the regulatory framework that is established in early human development. Progress in this area has been slow because it is difficult to obtain relevant biological samples. Inducible pluripotent stem cells (iPSCs) provide the ability to establish in vitro models of early human and non-human primate developmental stages. Using matched iPSC panels from humans and chimpanzees, we comparatively characterized gene regulatory changes through a four-day timecourse differentiation of iPSCs (day 0) into primary streak (day 1), endoderm progenitors (day 2), and definitive endoderm (day 3). As might be expected, we found that differentiation stage is the major driver of variation in gene expression levels, followed by species. We identified thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we considered gene-specific dynamic regulatory trajectories throughout the timecourse, we found that 75‥ of genes, including nearly all known endoderm developmental markers, have similar trajectories in the two species. Interestingly, we observed a marked reduction of both intra-and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of regulatory variation in endoderm progenitors. The reduction of variation in gene expression levels at a specific developmental stage, paired with overall high degree of conservation of temporal gene regulation, is consistent with the dynamics of developmental canalization. Overall, we conclude that endoderm development in iPSC-based models are highly conserved and canalized between humans and our closest evolutionary relative.
Translational profiling of microglia reveals artifacts of cell sorting
Authors: Kang Silvia S. , Baker Kelsey E. , Wang Xuewei , Kocher Jeanne-Pierre , Fryer John D.
Published: May 2017

Microglia are the resident innate immune population of the central nervous system that constantly survey and influence their local environment. Transcriptomic profiling has led to significant advances in our understanding of microglia in several disease states, but tissue dissociation and purification of microglia is known to lead to cellular activation. Here we use RiboTag translational RNAseq profiling to demonstrate that commonly used cell sorting methods lead to a fundamental alteration of the microglial transcriptome, with several transcripts that can be used to mark artifacts of isolation. Microglial RiboTag RNAseq profiling after peripheral immune challenge with lipopolysaccharide demonstrates unique transcriptional targets that are not evident using cell sorting methodology. Finally, we applied our technique to reveal novel shared and distinct pathways when comparing microglial transcriptomes after peripheral challenge with bacterial or viral mimetics. This study has broad implications for approaches that examine microglial transcriptomes in normal and pathological states.

Kang et al. demonstrate artifactual induction of microglial transcripts associated with cell sorting. Using RiboTag translational profiling methodology, several markers of cell sorting artifact were revealed. Furthermore, RiboTag isolation unveiled changes in microglial transcriptomes following systemic inflammation that would otherwise have been masked by artifacts of cell sorting.
DeepMetabolism: A Deep Learning System to Predict Phenotype from Genome Sequencing
Authors: Guo Weihua , Xu You (Eric) , Feng Xueyang
Published: May 2017

Life science is entering a new era of petabyte-level sequencing data. Converting such “big data” to biological insights represents a huge challenge for computational analysis. To this end, we developed DeepMetabolism, a biology-guided deep learning system to predict cell phenotypes from transcriptomics data. By integrating unsupervised pre-training with supervised training, DeepMetabolism is able to predict phenotypes with high accuracy (PCC>0.92), high speed (<30 min for >100 GB data using a single GPU), and high robustness (tolerate up to 75% noise). We envision DeepMetabolism to bridge the gap between genotype and phenotype and to serve as a springboard for applications in synthetic biology and precision medicine.
The paradox of constant oceanic plastic debris: evidence for evolved microbial biodegradation?
Authors: Solé Ricard , Fontich Ernest , Vidiella Blai , Duran-Nebreda Salva , Montañez Raúl , Piñero Jordi , Valverde Sergi
Published: May 2017

Although the presence of vast amounts of plastic in the open ocean has generated great concern due to its potential ecological consequences, recent studies reveal that its measured abundance is much smaller than expected. Regional and global studies indicate that the difference between expected and actual estimates is enormous, suggesting that a large part of the plastic has been degraded by either physical and biotic processes. A paradoxical observation is the lack of a trend in plastic accumulation found in the North Atlantic Subtropical Gyre, despite the rapid increase in plastic production and disposal. In this paper we show, using mathematical and computer models, that this observation could be explained by the nonlinear coupling between plastic (as a resource) and an evolved set of organisms (the consumers) capable of degrading it. The result is derived using two different resource-consumer mathematical approaches as well as a spatially-dependent plastic-microbial model incorporating a minimal hydrodynamical coupling with a two-dimensional fluid. The potential consequences of the evolution of marine plastic garbage and its removal are outlined.