bluuebunny/crossref_metadata_2025 huggingface dataset:
En Bloc lumpectomy of T12 vertebra for progressive hepatocellular carcinoma metastases following liver transplantation
Authors: Hu Jin-Gen , Lu Yang , Lin Xiang-Jin
Published: January 2020

Rationale:

Liver transplantation (LT) is the preferred surgical option for the treatment of early hepatocellular carcinoma (HCC). In contrast, surgical treatment of progressive HCC metastasized to the spine following LT constitutes a considerable challenge. Here, we report the first case of progressive HCC metastasized to the T12 vertebra after local radiotherapy, treated successfully with en bloc lumpectomy following LT for HCC.

Patient concerns:

A 40-year-old man who had undergone LT for the treatment of HCC 2 months prior presented to our clinic with symptoms of progressive back pain. Magnetic resonance imagining (MRI) and positron emission tomography (PET) examinations showed a solitary metastasis at T12 without recurrence in the liver or metastasis to other organs.

Diagnoses:

The patient was diagnosed with HCC metastasized to the T12 vertebra after liver transplantation.

Interventions:

Local radiation therapy of the T12 vertebra was performed; however, the lesion continued to grow one month after irradiation. Accordingly, the patient was treated with en bloc lumpectomy of the T12 vertebra. After surgery, the patient reported significant pain relief. At 11 months post-surgery, a C4 metastasis with spinal cord compression was revealed by MRI. Multiple grafted liver metastases were also detected by ultrasound along with several lung metastases, which were discovered by X-ray. The patient was treated with a pedicle screw system and a mesh cage filled with frozen autografts for C4 metastasis.

Outcomes:

The patient died 15 months after liver transplantation due to recurrence in the liver and metastasis to the lung.

Lessons:

En bloc lumpectomy may be a viable therapeutic option for patients with progressive solitary spinal metastases after LT refractory to radiotherapy. Use of immunosuppressive therapy after LT may significantly inhibit immune function, making patients more susceptible to HCC recurrence and bone metastasis.
Challenges in the diagnosis of Boerhaave syndrome
Authors: Tzeng Ching-Hsuane , Chen Wei-Kung , Lu Huei-Chun , Chen Hsin-Hung , Lee Kuan-I , Wu Yung-Shun , Lee Feng-You
Published: January 2020

Rationale:

Acute chest pain remains one of the most challenging complaints of patients presenting to emergency departments (EDs). The diverse etiologies of chest pain frequently lead to diagnostic and therapeutic challenges. Esophageal perforation is a rare but potentially life-threatening disease. It results in delayed diagnosis and an estimated mortality risk of 20% to 40%. Prompt diagnosis and immediate therapeutic interventions are key factors for a good prognosis.

Patient concerns:

Case 1 involved a 66-year-old man who presented to the ED with acute chest pain radiating to the back and hematemesis. Emergent contrast thoracic computerized tomography (CT) indicated the presence of a massive pneumothorax with pleural effusion. The continuous drainage of a dark-red bloody fluid following emergent thoracic intubation led to the discovery that the patient had experienced severe vomiting after whiskey consumption before admission to the hospital. Re-evaluation of the CT indicated spontaneous pneumomediastinum, whereas barium esophagography confirmed the presence of an esophageal perforation. Case 2 involved an 18-year-old Vietnamese man admitted to our ED with acute chest pain and swelling of the neck after vomiting due to beer consumption. A chest x-ray indicated diffuse subcutaneous emphysema of the neck and upper thorax. Contrast CT indicated pneumomediastinum with extensive emphysema and air in the paraspinal region and spinal canal.

Diagnoses:

Both of the 2 cases were diagnosed as spontaneous perforation of the esophagus (Boerhaave syndrome [BS]).

Interventions:

Case 1 received surgical interventions, whereas case 2 decided not to avail our medical services.

Outcomes:

Case 1 was discharged after a good recovery. Case 2 lost to follow-up.

Lessons:

We recommend all physicians in the ED to raise their index of suspicion for BS when dealing with patients having acute chest pain, dyspnea, confirmed pneumothorax, or newly-developed pleural effusion.
Interventions to Enhance Patient and Family Engagement Among Adults With Multiple Chronic Conditions
Authors: Daniel Obinna , Dest Alex , Munson Alexandra , Pulley Deren V. , Sadeghzadeh Claire , Golin Carol , Cené Crystal W.
Published: January 2020

Purpose:

In the United States, 42% of adults, and 81% of adults over 65 years of age live with multiple chronic condition (MCC). Current interventions to facilitate engagement in care focus primarily on the patient; however, many individuals with MCC manage and live with their conditions within the context of their family. This review sought to identify interventions used to facilitate patient and/or family engagement among adults with MCC.

Methods:

We adhered as closely as possible to PRISMA guidelines and conducted a systematic scoping review using a modified approach by Arksey and O’Malley. We searched PubMed, Web of Science, and Scopus using terms related to MCC, patient and family engagement, and intervention. We included articles that: (1) were published in English; (2) were peer-reviewed; (3) described an engagement intervention (with or without a comparator); and (4) targeted individuals with MCC. We abstracted data from included articles and classified them using the Multidimensional Framework for Patient and Family Engagement in Health and Health Care, and the Classification Model of Patient Engagement.

Results:

We identified 21 discrete interventions. Six (29%) were classified as having the highest degree of engagement. Eighteen (85%) focused on engagement at the direct care level. Only one was specifically designed to engage families.

Conclusions:

Many engagement interventions currently exist for adults with MCC. Few of these interventions foster the highest degree of engagement; most focus on engagement at the level of direct care and do not specifically target family member involvement.
Reliability of muscle thickness measurements in ultrasonography
Authors: Barotsis Nikolaos , Tsiganos Panagiotis , Kokkalis Zinon , Panayiotakis George , Panagiotopoulos Elias
Published: January 2020

This study aims to clarify some of the issues associated with the reliable measurement of muscle thickness on ultrasonographic images of the musculoskeletal system, namely the repeatability of measurements in different time frames, the effect of body side selection, and the effect of scan orientation. Ultrasound scans were performed on muscles associated with essential daily activities: geniohyoid, masseter, anterior arm muscles, rectus femoris, vastus intermedius, tibialis anterior, and gastrocnemius. Measurements of the muscle thickness were performed and repeated after 1, 6, and 24 h, on both dominant and nondominant side, using both transverse and longitudinal scans. Thirteen healthy volunteers (eight males and five females, mean age = 24 years, SD = 2.86, range = 19–29) were included. The intraclass correlation coefficient (ICC) was calculated between the baseline and the 1-, 6-, and 24-h interval, using a two-way mixed model of absolute agreement. The ICC ranged from 0.295 for the longitudinal scan of the left masseter muscle in the 6-h interval to 0.991 for the longitudinal scan of the nondominant anterior arm muscles in the 24-h interval. The results indicate that there is variable reliability of the measurements depending on the muscle, time frame, body side, and scan orientation. Consequently, the choice of these parameters can affect the validity of the measurements. Further investigation on a larger scale is required to establish the preferred parameters for each anatomical site.
Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas
Authors: Rooper Lisa M. , Bynum Jennifer P. , Miller Karin P. , Lin Ming T. , Gagan Jeffrey , Thompson Lester D.R. , Bishop Justin A.
Published: January 2020

Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.
Clinical Decision Support in the Electronic Medical Record to Increase Rates of Influenza Vaccination in a Pediatric Emergency Department
Authors: Buenger Lauren E. , Webber Emily C.
Published: January 2020

Objectives

Vaccination against influenza has been shown to decrease the morbidity and mortality from the virus; however, rates remain below the Healthy People 2020 target of 70%. The emergency department (ED) provides a unique opportunity to administer influenza vaccines; however, interventions must be efficient to be successful. During the 2014 to 2015 season, an electronic medical record (EMR) intervention was implemented in an effort to increase influenza vaccination rates.

Methods

Using Lean methodology, a multidisciplinary team designed a series of triggers, alerts, and orders in the EMR to address the barriers to adoption and their root causes. The EMR functionality was implemented for the 2014 to 2015 influenza season. Reports on compliance with each EMR step were completed for the 2014 to 2015 and 2015 to 2016 influenza seasons.

Results

In the 2013 to 2014 influenza season, the ED administered 42 doses of the vaccine, representing 0.3% of eligible visits. After implementation of the EMR tool, the ED administered 1320 doses of influenza vaccine. This represents approximately 8.8% of qualified patients based on age group and eventual discharge from the ED. The results were sustained during the 2015 to 2016 influenza season with 1031 doses administered, representing 6% of eligible visits.

Conclusions

The ED influenza vaccination program vaccinated approximately 20 times the number of eligible patients after automated EMR screening and ordering. Using knowledge of a multidisciplinary team, integration into the existing workflow, and visual cues in the EMR, we were able to increase the number of influenza vaccines administered substantially.
Brief Report: Higher Peripheral Monocyte Activation Markers Are Associated With Smaller Frontal and Temporal Cortical Volumes in Women With HIV
Authors: Kamkwalala Asante R. , Wang Xuzhi , Maki Pauline M. , Williams Dionna W. , Valcour Victor G. , Damron Alexandra , Tien Phyllis C. , Weber Kathleen M. , Cohen Mardge H. , Sundermann Erin E. , Meyer Vanessa J. , Little Deborah M. , Xu Yanxun , Rubin Leah H.
Published: January 2020

Background:

Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities.

Methods:

Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid–binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH).

Results:

In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid–binding protein were not associated with brain volumes for either group of women.

Conclusions:

Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.
Orofacial Manifestations of Stickler Syndrome
Authors: Jackson Oksana A. , Kaye Alison E. , Lee Alfred , Minugh-Purvis Nancy , Cohen Marilyn A. , Solot Cynthia B. , McDonald-McGinn Donna , Jawad Abbas F. , Zackai Elaine H. , Kirschner Richard E.
Published: January 2020

Purpose

The purpose of this study was to characterize airway problems, speech outcomes, and facial growth in patients with Stickler syndrome undergoing cleft palate repair.

Methods

A retrospective, longitudinal study was performed at the Children's Hospital of Philadelphia on 25 patients with Stickler syndrome and 53 nonsyndromic patients with clefts of the secondary palate repaired between 1977 and 2000. Airway problems were characterized by the incidence of Pierre Robin Sequence (PRS) and the necessity for surgical airway management. Speech was analyzed using the Pittsburgh weighted values for speech symptoms associated with velopharyngeal incompetence (VPI). Longitudinal anthropometric measurements represented up to 12 years of longitudinal cephalofacial growth.

Results

Seventy-two percent of patients with Stickler syndrome were diagnosed with PRS, 55.6% of whom required surgical airway management. Conversely, 20.8% of nonsyndromic patients were diagnosed with PRS (P < 0.0001), 18% of whom required surgical intervention (P < 0.05). Speech outcomes were poorer in patients with Stickler syndrome with 40% demonstrating borderline VPI and 13.3% demonstrating VPI, compared with 21.8% and 9.1%, respectively, in the nonsyndromic group. Both groups exhibited significantly shallower upper and mid facial depths and wider upper facial breadths when compared with normal standards of facial growth. Although there was a tendency toward decreased facial depths in patients with Stickler syndrome relative to nonsyndromic patients, the differences were nonsignificant.

Conclusions

Patients with Stickler syndrome show significant potential for early airway compromise and a poorer prognosis for speech outcome after cleft palate repair. Their cephalofacial growth does not differ significantly from that of nonsyndromic cleft palate patients.
Three End-to-End Techniques for Microvascular Anastomosis of Vessels With Different Size Discrepancy
Authors: Zhang Yi , Wang Tingliang , Liu Ying , He Jinguang , Dong Jiasheng , Xu Hua
Published: January 2020

Background

Size discrepancy in microvascular anastomosis is a common issue in free flap transfer and replantation surgery. A number of different techniques have been described to overcome the problem, but optimal method continues to be defined.

Methods

Since June 2015 to May 2018, clinical courses of 103 microvascular cases performed by one senior surgeon were reviewed. Three end-to-end techniques including mechanical dilation, single-mattress suture, and wedge resection were applied in 364 anastomoses with caliber ratio between 1:1 and 1:1.5, 1:1.5 and 1:2, and 1:2 and 1: 3, respectively.

Results

A total of 112 flaps were incorporated in this study. The incidence of anastomotic failure was 3.0% (11/364), and the overall flap failure rate was 3.6% (4/112). The failure cases included 2 replanted scalps, 1 replanted ear, and 1 superficial temporal artery flap for nasal reconstruction.

Conclusions

Our results depicted operational convenience and reliability of the 3 end-to-end anastomotic techniques in addressing mild-to-large vessel discrepancy.
Synchronous Closure of A Large Medial Perforator–Based Superficial Circumflex Iliac Artery Perforator Free Flap Donor Site Using an Ipsilateral Lateral Perforator–Based Superficial Circumflex Iliac Artery Perforator Propeller Flap
Authors: Zhang Yi xin , Hallock Geoffrey G. , Song Dajiang , Vargas Marcela Sánchez , Correa Susana
Published: January 2020

A superior advantage of the superficial circumflex iliac artery perforator flap is that any donor site residue can easily be hidden by clothing. Usually designed as narrow or moderate-sized flaps based on medial perforators of the superficial branch, this readily allows primary donor site closure. However, for larger flaps, tension-free closure requires that the thigh remain flexed or even a skin graft used. Another alternative would be to use an adequate lateral perforator of the deep branch, if available, as the vascular hub of a propeller flap that extended into the adjacent flank, that could then be rotated into the medial groin to facilitate simultaneous direct closure of both flap donor sites.
Reconstruction of Large Ptotic Breasts After Nipple-Sparing Mastectomy
Authors: Oven Steven D. , Scarlett William L.
Published: January 2020

As nipple-sparing mastectomies continue to gain popularity, the reconstruction of a large ptotic breast remains a challenge. The purpose of this article is to introduce the senior author's modifications of a novel technique previously described for addressing the redundant skin envelope in ptotic breasts during immediate reconstruction after nipple-sparing mastectomy. In this review, 15 patients (29 breasts) were reconstructed using our modified “buttonhole” technique. Postoperative complications included 1 case of nipple necrosis and 1 case of tissue expander loss secondary to infection. All patients eventually underwent full expansion and exchange to permanent implants. Ultimately, this surgical approach offers immediate reconstruction after nipple-sparing mastectomy while concurrently performing a safe and aesthetically pleasing mastopexy with acceptable risk to the nipple-areolar complex.
Millennial-Assisted Liposuction
Authors: Barnes Connor , Weinstein Brielle , Robertson Ellen , Clark Clifford
Published: January 2020

Over the past 6 decades through innovation, creativity, ingenuity, and hard work, liposuction is now one of the most popular cosmetic procedures around the world. Several different liposuction technologies now exist, which include suction-assisted lipectomy, power-assisted liposuction, and so on. We have devised a new technique geared toward the incoming Generation Y surgeon called millennial-assisted liposuction. With such great advances in current liposuction techniques, one might ponder the need to introduce a new technique. This may become more common as the “Me Generation” sets forth in the working community and takes over for the prior generation of plastic surgeons. This article was written and developed by a millennial and the senior author, a nonmillennial, to help conform to the changing dynamic of incoming plastic surgeons. The technique was developed to solve the problem regarding millennials requiring constant reinforcement, around-the-clock assistance, immediate feedback, work-hour limits, frequent breaks, and lack of trophies.
Immediate Versus Staged Soft Tissue Reconstruction After Soft Tissue Sarcoma Resection Has Similar Wound and Oncologic Outcomes
Authors: Lawrenz Joshua M. , Mesko Nathan W. , Marshall Danielle C. , Featherall Joseph , George Jaiben , Gordon Jaymeson , Vijayasekaran Aparna , Nystrom Lukas M. , Schwarz Graham S.
Published: January 2020

Background

The aim of this study was to compare the wound complication rate and oncologic outcome in patients undergoing immediate versus staged soft tissue reconstruction after soft tissue sarcoma (STS) resection.

Methods

This is a retrospective analysis of a single sarcoma referral center between 2006 and 2016 which identified a cohort that underwent resection of an extremity or trunk STS with reconstruction surgery (split thickness skin graft or flap coverage). Patients were divided into 2 groups based on the reconstruction timing: immediate (same day) versus staged (later date). Demographic characteristics, wound complications, and oncologic outcomes were compared.

Results

Of the 491 patients who underwent resection of an extremity or trunk STS, 81 (16%) received reconstructive surgery, with 26 patients undergoing immediate reconstruction and 55 patients undergoing staged reconstruction. Overall wound complication (58% vs 45%, P = 0.347) and infection rates (35% vs 25%, P = 0.602) were similar between immediate and staged groups, respectively. Likewise, local recurrence (8% vs 7%, P = 1.000), metastasis (19% vs 20%, P = 0.755), and all-cause mortality (27% vs 27%, P = 1.000) rates after reconstruction was similar. Patients in the staged group with positive margins after resection were re-excised before definitive reconstruction, whereas those in the immediate group were not. The staged group required fewer surgical intensive care unit stays after resection surgery (22% vs 58%, P = 0.006). The mean ± SD final follow-up was 38 ± 33 months.

Conclusions

Wound complication rates and oncologic outcomes remain similar, regardless of timing for reconstruction. Staged reconstructions were associated with fewer surgical intensive care unit stays, while also affording opportunity for reintervention after positive margins with little additional morbidity.
Surgical Management of Pediatric Hidradenitis Suppurativa
Authors: Ge Shealinne , Ngaage Ledibabari M. , Orbay Hakan , Silverman Ronald P. , Rasko Yvonne M. , Rada Erin M.
Published: January 2020

Background

Hidradenitis suppurativa (HS) is a chronic and physically debilitating condition. Achieving long-term remission is difficult and sometimes remains elusive despite use of multiple pharmacological agents. However, surgery remains underused in the pediatric population.

Methods

We conducted a retrospective review for a 10-year period of all patients younger than 18 years who had undergone surgery for HS at a tertiary university hospital. In addition, we performed a literature review for English language articles related to the surgical management of pediatric HS patients.

Results

Eleven patients with a total of 23 operative sites were included in the study. The cohort was predominantly female (10:1) with an average age of 15.4 years and mean body mass index 31.9 kg/m2. Lesion size ranged from 12.6 to 400 cm2. Overall complication rate was 87% with a 7% reoperation rate to manage complications. Remission was achieved after a single procedure in 57% of sites. Three articles met our inclusion criteria for the literature review.

Conclusions

Our article adds to the sparse literature and represents the largest study on surgical management of pediatric HS patients. Although surgery is not without its challenges, it presents a safe option and for pediatric HS patients with extensive scar or sinus tract formation.
Anticholinergic Use Among the Elderly With Alzheimer Disease in South Korea
Authors: Joung Kyung-in , Shin Ju-Young , Kim Sukil , Cho Sung-il
Published: January 2020

Objectives:

To investigate the characteristics of anticholinergic use in the elderly with Alzheimer disease (AD) compared with those in the non-AD elderly.

Methods:

Using the Korean National Health Insurance Service Elderly cohort database, 388,629 adults aged 70 years and older in 2012 were included. The use of strong anticholinergic agents (ACs) in 2012 was quantified by standardized prescribed doses. Univariate and multivariate logistic regression models were applied to examine the level of their heavy use (≥90 doses of the prescribed amount in 2012) in patients with AD and potential explanations of the heavy use.

Results:

Antihistamines and antidepressants were the most prescribed strong ACs among non-AD and AD elderly, respectively. The heavy use of strong ACs was more prevalent in patients with AD than in non-AD elderly [odds ratio (95% confidence interval)=1.48 (1.41-1.56)]. When the morbidities associated with AD were adjusted for, odds ratio were reduced [0.91 (0.85-0.96)].

Conclusions:

Heavy use of strong ACs was more prevalent in patients with AD than in non-AD elderly. Multiple ACs for treating multimorbidities in AD were mainly attributable to their heavy use. In patients with AD, the integrated management of medications for reducing the preventable heavy use of these drugs should be reinforced.
mHealth in affective disorders: hype or hope? A focused narrative review
Authors: Hidalgo-Mazzei Diego , Llach Cristian , Vieta Eduard
Published: January 2020

The constant growth and widespread availability of mobile technologies (i.e. smartphones and wearables) over the last decades have been a subject of intense interest and research in the affective disorders (AD) field. The potential of mHealth for collecting a new kind of passive and active information while providing cost-effective and tailored interventions have raised many hopes. However, until now, despite some encouraging results, research in the field has not been translated to reach real-world clinical settings or to develop additional evidence-based mHealth tools for people suffering from AD. Meanwhile, commercial untested apps and wearables are already being increasingly used and adopted by patients for the self-management of their illnesses. Hence, there is a latent need and demand from service users to integrate mHealth in their care, which the field cannot yet fulfil. In this article, through a focused narrative review, we discuss the evidence available for the use, validity and efficacy of mHealth tools in AD. Challenges in the academic field hampering the advancement of these technologies and its implementation into clinical practice are discussed. Lastly, we propose a framework to overcome these issues, which may facilitate mHealth solutions reaching service users.
Evolutionary rates are correlated between cockroach symbionts and mitochondrial genomes
Authors: Arab Daej A. , Bourguignon Thomas , Wang Zongqing , Ho Simon Y. W. , Lo Nathan
Published: January 2020

Bacterial endosymbionts evolve under strong host-driven selection. Factors influencing host evolution might affect symbionts in similar ways, potentially leading to correlations between the molecular evolutionary rates of hosts and symbionts. Although there is evidence of rate correlations between mitochondrial and nuclear genes, similar investigations of hosts and symbionts are lacking. Here, we demonstrate a correlation in molecular rates between the genomes of an endosymbiont (Blattabacterium cuenoti) and the mitochondrial genomes of their hosts (cockroaches). We used partial genome data for multiple strains ofB. cuenotito compare phylogenetic relationships and evolutionary rates for 55 cockroach/symbiont pairs. The phylogenies inferred forB. cuenotiand the mitochondrial genomes of their hosts were largely congruent, as expected from their identical maternal and cytoplasmic mode of inheritance. We found a correlation between evolutionary rates of the two genomes, based on comparisons of root-to-tip distances and on comparisons of the branch lengths of phylogenetically independent species pairs. Our results underscore the profound effects that long-term symbiosis can have on the biology of each symbiotic partner.
Unhatched eggs represent the invisible fraction in two wild bird populations
Authors: Hemmings Nicola , Evans Simon
Published: January 2020

Prenatal mortality is typically overlooked in population studies, which biases evolutionary inference by confounding selection and inheritance. Birds represent an opportunity to include this ‘invisible fraction’ if each egg contains a zygote, but whether hatching failure is caused by fertilization failure versus prenatal mortality is largely unknown. We quantified fertilization failure rates in two bird species that are popular systems for studying evolutionary dynamics and found that overwhelming majorities (99.9%) of laid eggs were fertilized. These systems thus present opportunities to eliminate the invisible fraction from life-history data.
Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate
Authors: Nof Eliram , Heller-Algazi Metar , Coletti Filippo , Waisman Dan , Sznitman Josué
Published: January 2020

We investigate respiratory flow phenomena in a reconstructed upper airway model of an intubated neonate undergoing invasive mechanical ventilation, spanning conventional to high-frequency ventilation (HFV) modes. Using high-speed tomographic particle image velocimetry, we resolve transient, three-dimensional flow fields and observe a persistent jet flow exiting the endotracheal tube whose strength is directly modulated according to the ventilation protocol. We identify this synthetic jet as the dominating signature of convective flow under intubated ventilation. Concurrently, ourin silicowall shear stress analysis reveals a hitherto overlooked source of ventilator-induced lung injury as a result of jet impingement on the tracheal carina, suggesting damage to the bronchial epithelium; this type of injury is known as biotrauma. We find HFV advantageous in mitigating the intensity of such impingement, which may contribute to its role as a lung protective method. Our findings may encourage the adoption of less invasive ventilation procedures currently used in neonatal intensive care units.
Burrowing below ground: interaction between soil mechanics and evolution of subterranean mammals
Authors: Rosario Carotenuto Angelo , Guarracino Federico , Šumbera Radim , Fraldi Massimiliano
Published: January 2020

The evolution of species is governed by complex phenomena in which biological and environmental features may interact dynamically. Subterranean mammals dig tunnels whose diameter minimizes energetic costs during excavations and display anatomical adaptations in order to burrow structurally stable tunnels according to specific features of the soil. These animals weight from less than 50 g up to 1–2 kg, and dig tunnels with diameters from 3 to 15 cm. The use of allometric laws has enabled these data to be correlated. However, since tunnels need to be stable with respect to the geomechanical characteristics of the resident soils, a mathematical treatment linking the admissible dimensions of tunnels to the environment here suggests a mechanically grounded correlation between the body mass of subterranean mammals and the maximum dimensions of tunnels. Remarkably, such theoretical findings reflect very well the empirical allometric relationship and contribute to explain the wide differences observed in body sizes of subterranean mammals. In this respect, a far from ancillary role of environmental mechanics on the morphological evolution of subterranean mammals can be hypothesized.
Social influence and interaction bias can drive emergent behavioural specialization and modular social networks across systems
Authors: Tokita Christopher K. , Tarnita Corina E.
Published: January 2020

In social systems ranging from ant colonies to human society, behavioural specialization—consistent individual differences in behaviour—is commonplace: individuals can specialize in the tasks they perform (division of labour (DOL)), the political behaviour they exhibit (political polarization) or the non-task behaviours they exhibit (personalities). Across these contexts, behavioural specialization often co-occurs with modular and assortative social networks, such that individuals tend to associate with others that have the same behavioural specialization. This raises the question of whether a common mechanism could drive co-emergent behavioural specialization and social network structure across contexts. To investigate this question, here we extend a model of self-organized DOL to account for social influence and interaction bias among individuals—social dynamics that have been shown to drive political polarization. We find that these same social dynamics can also drive emergent DOL by forming a feedback loop that reinforces behavioural differences between individuals, a feedback loop that is impacted by group size. Moreover, this feedback loop also results in modular and assortative social network structure, whereby individuals associate strongly with those performing the same task. Our findings suggest that DOL and political polarization—two social phenomena not typically considered together—may actually share a common social mechanism. This mechanism may result in social organization in many contexts beyond task performance and political behaviour.
A quantitative account of mammalian rod phototransduction with PDE6 dimeric activation: responses to bright flashes
Authors: Lamb Trevor D. , Kraft Timothy W.
Published: January 2020

We develop an improved quantitative model of mammalian rod phototransduction, and we apply it to the prediction of responses to bright flashes of light. We take account of the recently characterized dimeric nature of PDE6 activation, where the configuration of primary importance has two transducin molecules bound. We simulate the stochastic nature of the activation and shut-off reactions to generate the predicted kinetics of the active molecular species on the disc membrane surfaces, and then we integrate the differential equations for the downstream cytoplasmic reactions to obtain the predicted electrical responses. The simulated responses recover the qualitative form of bright-flash response families recorded from mammalian rod photoreceptors. Furthermore, they provide an accurate description of the relationship between the time spent in saturation and flash intensity, predicting the transition between first and second ‘dominant time constants’ to occur at an intensity around 5000 isomerizations per flash, when the rate of transducin activation is taken to be 1250 transducins s
−1
per activated rhodopsin. This rate is consistent with estimates from light-scattering experiments, but is around fourfold higher than has typically been assumed in other studies. We conclude that our model and parameters provide a compelling description of rod photoreceptor bright-flash responses.
Deficits in functional trait diversity following recovery on coral reefs
Authors: McWilliam Mike , Pratchett Morgan S. , Hoogenboom Mia O. , Hughes Terry P.
Published: January 2020

The disturbance regimes of ecosystems are changing, and prospects for continued recovery remain unclear. New assemblages with altered species composition may be deficient in key functional traits. Alternatively, important traits may be sustained by species that replace those in decline (response diversity). Here, we quantify the recovery and response diversity of coral assemblages using case studies of disturbance in three locations. Despite return trajectories of coral cover, the original assemblages with diverse functional attributes failed to recover at each location. Response diversity and the reassembly of trait space was limited, and varied according to biogeographic differences in the attributes of dominant, rapidly recovering species. The deficits in recovering assemblages identified here suggest that the return of coral cover cannot assure the reassembly of reef trait diversity, and that shortening intervals between disturbances can limit recovery among functionally important species.
Using genomics to understand meticillin- and vancomycin-resistant Staphylococcus aureus infections
Authors: Giulieri Stefano G. , Tong Steven Y. C. , Williamson Deborah A.
Published: January 2020

Resistance to meticillin and vancomycin in

Staphylococcus aureus

significantly complicates the management of severe infections like bacteraemia, endocarditis or osteomyelitis. Here, we review the molecular mechanisms and genomic epidemiology of resistance to these agents, with a focus on how genomics has provided insights into the emergence and evolution of major meticillin-resistant

S. aureus

clones. We also provide insights on the use of bacterial whole-genome sequencing to inform management of

S. aureus

infections and for control of transmission at the hospital and in the community.
Low-density Lipoprotein Receptor-related Protein 5 (LRP5)-deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature
Authors: Ubels John L. , Diegel Cassandra R. , Foxa Gabrielle E. , Ethen Nicole J. , Lensing Jonathan N. , Madaj Zachary B. ,   VARI Vivarium and Transgenics Core, Williams Bart O.
Published: January 2020

Humans carrying homozygous loss-of-function mutations in the Wnt co-receptor LRP5 (low-density lipoprotein receptor–related protein 5) develop osteoporosis and a defective retinal vasculature known as familial exudative vitreoretinopathy (FEVR) due to disruption of the Wnt signaling pathway. The purpose of this study was to use CRISPR/Cas9-mediated gene editing to create strains of Lrp5-deficient rats and to determine whether knockout ofLrp5resulted in phenotypes that model the bone and retina pathology in LRP5-deficient humans. Knockout ofLrp5 in rats produced low bone mass, decreased bone mineral density, and decreased bone size. The superficial retinal vasculature of Lrp5-deficient rats was sparse and disorganized, with extensive exudates and decreases in vascularized area, vessel length, and branch point density. This study showed thatLrp5 could be predictably knocked out in rats using CRISPR/Cas9, causing the expression of bone and retinal phenotypes that will be useful for studying the role of Wnt signaling in bone and retina development and for research on the treatment of osteoporosis and FEVR.
Voice and Face Gender Perception engages multimodal integration via multiple feedback pathways
Authors: Abbatecola Clement , Beneyton Kim , Gerardin Peggy , Kennedy Henry , Knoblauch Kenneth
Published: January 2020

Multimodal integration provides an ideal framework for investigating top-down influences in perceptual integration. Here, we investigate mechanisms and functional networks participating in face-voice multimodal integration during gender perception by using complementary behavioral (Maximum Likelihood Conjoint Measurement) and brain imaging (Dynamic Causal Modeling of fMRI data) techniques. Thirty-six subjects were instructed to judge pairs of face-voice stimuli either according to the gender of the face (face task), the voice (voice task) or the stimulus (stimulus task; no specific modality instruction given). Face and voice contributions to the tasks were not independent, as both modalities significantly contributed to all tasks. The top-down influences in each task could be modeled as a differential weighting of the contributions of each modality with an asymmetry in favor of the auditory modality in terms of magnitude of the effect. Additionally, we observed two independent interaction effects in the decision process that reflect both the coherence of the gender information across modalities and the magnitude of the gender difference from neutral. In a second experiment we investigated with functional MRI the modulation of effective connectivity between the Fusiform Face Area (FFA) and the Temporal Voice Area (TVA), two cortical areas implicated in face and voice processing. Twelve participants were presented with multimodal face-voice stimuli and instructed to attend either to face, voice or any gender information. We found specific changes in effective connectivity between these areas in the same conditions that generated behavioral interactions. Taken together, we interpret these results as converging evidence supporting the existence of multiple parallel hierarchical systems in multi-modal integration.
Early life adversity decreases fear expression in pre-adolescence by accelerating amygdalar parvalbumin cell development
Authors: Nieves Gabriela Manzano , Bravo Marylin , Bath Kevin G.
Published: January 2020

Resource insecurity (e.g., poverty) can be a significant source of stress. Decreased resources during childhood has been associated with increased risk for developing stress-related disorders, including major depressive disorder and anxiety Although the link between early life adversity and increased risk for psychopathology has been well established, the developmental mechanisms remain unclear. Using a mouse model of poverty-like rearing, limited bedding and nesting materials (LB), we tested the effects of LB on the development of fear learning and of key neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of pre-adolescent mice to express, but not form, an auditory conditioned fear memory. LB disrupted typical fear circuit development, accelerating parvalbumin positive (PV+) inhibitory interneuron maturation in the BLA and delaying the maturation of connections between the mPFC and BLA. The decreased fear expression in LB reared mice during early development was rescued through optogenetic inactivation of PV+ cells in the BLA. Together our data demonstrate that LB has profound and deleterious effects on mPFC and BLA development, decreasing threat-associated behavior expression, but not learning, in childhood. The current results provide a model of transiently blunt emotional reactivity in childhood, with fear-associated memories emerging later in adolescence, and possibly contributing to later pathology development.
RIP1 kinase activity promotes steatohepatitis through mediating cell death and inflammation in macrophages
Authors: Tao Liang , Yi Yuguo , Chen Yuxin , Zhang Haibing , Jie Jiapeng , Zhang Weigao , Xu Qian , Li Yang , Orning Pontus , Lien Egil , Zhao Mengshu , Gao Pingshi , Ling Ling , Ding Zhao , Wu Chao , Ding Qiurong , Wang Junsong , Zhang Jianfa , Weng Dan
Published: January 2020

Hepatocyte cell death and liver inflammation have been well recognized as central characteristics of nonalcoholic steatohepatitis (NASH), however, the underlying molecular basis remains elusive. The kinase receptor-interacting protein 1 (RIP1) is a key regulator of apoptosis, necroptosis and inflammation, we thus hypothesized that the kinase activity of RIP1 may be involved in the pathogenesis of NASH. Wild-type and RIP1 kinase-dead (Rip1K45A/K45A) mice were fed with methionine-and choline-deficient diet (MCD) or high-fat diet (HFD) to establish distinct NASH models. In both models, compared to WT mice,Rip1K45A/K45Amice exhibited significantly less liver injury, less steatosis, decreased inflammation, and less cell death in liver tissue. Moreover, hepatic fibrosis as characterized by Sirius Red staining, expression of α-SMA and other fibrosis markers, were significantly alleviated inRip1K45A/K45Amice than WT controls. Furthermore, using bone marrow transplantation to create chimeric mice, we found that it is the RIP1 kinase in hematopoietic-derived macrophages contributing mostly to the disease progression in NASH. Results fromin vitrostudies were in agreement with thein vivodata, demonstrating that RIP1 kinase was required for inflammasome activation and cell death induced by saturated fatty acid (palmitic acid) in bone marrow-derived macrophages (BMDMs). At last, we also found that the phosphorylation and expression of RIP1 was obviously increased in patients with NAFLD or NASH, but not in healthy controls. In summary, our results indicate that RIP1 kinase is activated during the pathogenesis of steatohepatitis, and consequently induces inflammation and cell death in macrophages, contributing to the disease progression. Our study suggests that macrophage RIP1 kinase represents a specific and potential target for the treatment of NASH.
Social environment drives sex and age-specific variation inDrosophila melanogastermicrobiome composition and predicted function
Authors: Leech Thomas , McDowall Laurin , Hopkins Kevin P , Sait Steven M , Harrison Xavier A. , Bretman Amanda
Published: January 2020

Social environments influence multiple traits of individuals including immunity, stress and ageing, often in sex-specific ways. The composition of the microbiome (the assemblage of symbiotic microorganisms within a host) is determined by environmental factors and the host’s immune, endocrine and neural systems. The social environment could alter host microbiomes extrinsically by affecting transmission between individuals, likely promoting homogeneity in the microbiome of social partners. Alternatively, intrinsic effects arising from interactions between the microbiome and host physiology (the microbiota-gut-brain axis) could translate social stress into dysbiotic microbiomes, with consequences for host health. We investigated how manipulating social environments during larval and adult life-stages altered the microbiome composition ofDrosophila melanogasterfruit flies. We used social contexts that particularly alter the development and lifespan of males, predicting that any intrinsic social effects on the microbiome would therefore be sex-specific. The presence of adult males during the larval stage significantly altered the microbiome of pupae of both sexes. In adults, same-sex grouping increased bacterial diversity in both sexes. Importantly, the microbiome community structure of males was more sensitive to social contact at older ages, an effect partially mitigated by housing focal males with young rather than co-aged groups. Functional analyses suggest that these microbiome changes impact ageing and immune responses. This is consistent with the hypothesis that the substantial effects of the social environment on individual health are mediated through intrinsic effects on the microbiome, and provides a model for understanding the mechanistic basis of the microbiota-gut-brain axis.

Significance statement

The social environment has pervasive, multifaceted effects on individual health and fitness. If a host’s microbiome is sensitive to the social environment then it could be an important mediator of social effects, as the reciprocal relationships between hosts and their microbiomes have substantial implications for host health. Using aDrosophila melanogasterfruit fly model we show that the fly microbiome is sensitive to the social environment in a sex, age and life-stage dependent manner. In particular, older adult male microbiome communities are altered by same-sex social contact, but this depends on the age of the social partners. These changes have functional effects on fly immunity and lifespan, evidence that indeed this is an influential mediator of social effects on health.