bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition Practices and Predictors of Postnatal Growth in Preterm Infants During Hospitalization
Authors: McKenzie Briar L. , Edmonds Liza , Thomson Ruth , Haszard Jillian J. , Houghton Lisa A.
Published: September 2017

Premature infants are at high risk of undernutrition and extrauterine growth restriction.

Aim:

The aim of the study was to evaluate the relation between nutrition practices and growth rate in preterm infants from birth to 36 weeks postmenstrual age (PMA).

Methods:

Longitudinal data were collected retrospectively in 103 infants born <33 weeks gestation admitted to Dunedin Neonatal Intensive Care Unit, New Zealand. Weight, length, and head circumference at birth and 36 weeks PMA z scores were calculated using the INTERGROWTH Preterm Growth Standard. Growth velocity (g · kg−1 · day−1) was determined via exponential model. Time to regain birth weight and nutritional practices including enteral nutrition, withholding feeds, nutrient intake, and feeding at discharge were described. Regression was used to explore associations between growth and nutritional variables.

Results:

Growth faltering (weight‐for‐age z score <−1.28/10th centile) increased from 9% at birth to 19% at 36 weeks PMA. Mean (standard deviation) growth velocity in‐hospital (14.2 [3.3] g · kg−1 · day−1) was well below the desirable rate of 18 g · kg−1 · day−1. Forty‐one percent of infants had feeds withheld, which was significantly associated with a longer time period to achieve full enteral feedings (P < 0.001) and poorer weight and length z score at 36 weeks PMA (both P < 0.05). The day of life to establish full enteral feedings was longer than recommended yet positively associated with weight at 36 weeks PMA (P = 0.019), whereas controlling for withholding feeds and other known confounders.

Conclusions:

Extrauterine growth restriction was highly prevalent in this population. The negative association of withholding of feeds on growth reinforces the need to evaluate early life feeding protocols and further assess the longer‐term influence of this practice on postdischarge growth outcomes.
Anti‐TNFα Treatment in Children and Adolescents With Combined Inflammatory Bowel Disease and Autoimmune Liver Disease
Authors: Nedelkopoulou Natalia , Vadamalayan Babu , Vergani Diego , Mieli‐Vergani Giorgina
Published: September 2017

Objectives:

Inflammatory bowel disease (IBD) and autoimmune liver disease (AILD) are closely associated, the former often dictating progression of the latter. Antibodies to tumor necrosis factor alpha (anti‐TNFα) are effective in the management of IBD, but may cause liver injury.

Methods:

Retrospective review of medical records of patients with juvenile AILD who received anti‐TNFα for IBD to evaluate the safety and efficacy of anti‐TNFα.

Results:

Eleven patients (6 boys), ages 9 to 15 years (median 13 years) were identified. Ten had ulcerative colitis and 1 Crohn disease; 2 had autoimmune hepatitis type 1 and 9 autoimmune hepatitis‐sclerosing cholangitis variant. All patients were started on infliximab (IFX, 5 mg/kg) and 2 required dose increase (10 mg/kg); 3 of 11 switched to adalimumab due to allergic reaction or nonresponse. Three received adalimumab after losing response or developing antibodies to IFX. Liver function tests (LFTs) improved in 5, 1 continued to have stably abnormal LFTs and 2 maintained normal LFTs. Patients on adalimumab showed stable or improved liver function compared to pretreatment status. Six of 8 treated with a full course of IFX maintained clinical remission of IBD for 6 months to 2.5 years; of the 6 patients treated with adalimumab, 1 sustained IBD clinical remission for 24 months, 2 achieved remission only after tacrolimus addition and 3 did not respond.

Conclusions:

IBD in patients with AILD can be aggressive, requiring escalation to anti‐TNFα or switching to other biologics. In this series, anti‐TNFα did not impair liver function and improved gut disease in most of the patients, indicating that it can be beneficial and safe.
Development and Evaluation of Innovative Peer-Led Physical Activity Programs for Mental Health Service Users
Authors: Graham Candida R. , Larstone Roseann , Griffiths Brenda , de Leeuw Sarah , Anderson Lesley , Powell-Hellyer Stephanie , Long Nansi
Published: September 2017

Mental health service users (MHSUs) have elevated rates of cardiometabolic disturbance. Improvements occur with physical activity (PA) programs. We report the development and evaluation of three innovative peer-developed and peer-led PA programs: 1) walking; 2) fitness; and 3) yoga. Qualitative evaluation with 33 MHSUs in British Columbia, Canada, occurred. These programs yielded improvements for participants, highlighted by powerful narratives of health improvement, and improved social connections. The feasibility and acceptability of innovative peer-developed and peer-led programs were shown. Analyses revealed concepts related to engagement and change. Relating core categories, we theorize effective engagement of MHSUs requires accessibility on three levels (geographic, cost, and program flexibility) and health behavior change occurs within co-constituent relationships (to self, to peers, and to the wider community). This study highlights the benefits of peer involvement in developing and implementing PA programs and provides a theoretical framework of understanding engagement and behavior change in health programs for MHSUs.
Rattled
Authors: Blasco Michael A. , Kandinov Aron , Svider Peter F. , Gonik Nathan J. , Hanba Curtis , Zuliani Giancarlo F. , Shkoukani Mahdi A. , Carron Michael A.
Published: September 2017

Objective

The aim of this study was to determine the national incidence of facial trauma among toddlers and delineate patterns of injury and their causes.

Methods

A retrospective review was designed to explore patterns of maxillofacial trauma within toddler-aged children using the National Electronic Injury Surveillance System from the Consumer Product Safety Commission. The database was searched for emergency department visits involving facial trauma sustained by children 12 months through 3 years of age from 2010 through 2014 and analyzed for patient demographics, primary diagnosis, and associated products/activities. Subset analyses were performed between age groups to determine the relationship between causes of injury and age using extrapolated national incidences.

Results

A sample of 45,249 patients extrapolated to an estimated 1.3 million emergency department visits for facial trauma in toddlers from 2010 to 2014, averaging 260,000 annually. Injuries involving foreign bodies and fractures had a higher incidence in toddlers 2 years or older, and fractures comprised fewer than 1% of facial injuries in any age group. Furniture was the most common source of trauma overall, with a higher frequency among toddlers aged 12 to 17 months. Trauma in the setting of sports was more common in toddlers aged 3 years.

Conclusions

The low incidence of facial fractures further supports recommendations against routine imaging in toddler facial trauma and suggests that more focus should be placed on investigating for concurrent traumas and soft tissue injuries where fractures are involved. Our findings highlight prevention opportunities, particularly in furniture-related injuries for toddlers aged 12 to 17 months and sports-related traumas in toddlers aged 3 years. Our study also suggests restricting certain toys from 3-year-old toddlers to decrease the risk of aspiration.
Effects of a Program for Improving Biomechanical Characteristics During Walking and Running in Children Who Are Obese
Authors: Steinberg Nili , Rubinstein Meron , Nemet Dan , Ayalon Moshe , Zeev Aviva , Pantanowitz Michal , Brosh Tamar , Eliakim Alon
Published: September 2017

Purpose:

To investigate the influence of a weight-reduction program with locomotion-emphasis on improving biomechanical characteristics of children who are obese (OW).

Methods:

Ten children who are OW participated in a 6-month multidisciplinary childhood obesity management program (GRP1); another 10 children who are OW participated in the same multidisciplinary childhood obesity management program with additional locomotion-emphasis exercises for improving biomechanical characteristics (GRP2); and 10 control children who are OW with no intervention program. Outcomes were anthropometric measurements and temporal and foot pressure parameters.

Results:

GRP2 had significantly improved foot pressure in the different walking/running speeds compared with GRP1. In the temporal parameters, pretests by speed by group interactions were significantly improved for GRP2 compared with GRP1.

Conclusions:

We found evidence to support beneficial effects of combined dietary and physical activity/locomotion-emphasis exercises on the movement characteristics of children who are OW.
Uptake of the Congenital Muscular Torticollis Clinical Practice Guideline Into Pediatric Practice
Authors: Kaplan Sandra L. , Dole Robin L. , Schreiber Joseph
Published: September 2017

Purpose:

This study describes survey responses about implementation of the congenital muscular torticollis clinical practice guideline (CMT-CPG) by pediatric physical therapists (PT) and successes and challenges with knowledge-brokering activities.

Methods:

An online survey was distributed to pediatric PTs who self-identified with practice experience with congenital muscular torticollis. Data were analyzed for implementation frequency of guideline recommendations and differences pre and postpublication of the CMT-CPG.

Results:

After publication, guideline recommendation implementation improved such that no recommendation was being implemented by less than 50% of respondents, and most were implemented by greater than 90%. The majority of respondents participated in knowledge brokering; however, many indicated minimal effectiveness of those activities.

Conclusions:

The CMT-CPG has successfully aided in changing practice. Participants identified areas of challenge and success in translating recommendations into practice and in knowledge brokering that may be helpful for the development of future CPGs.
The Geek Perspective: Answering the Call for Advanced Technology in Research Inquiry Related to Pediatric Brain Injury and Motor Disability
Authors: Wininger Michael , Pidcoe Peter
Published: September 2017

The Academy of Pediatric Physical Therapy Research Summit IV issued a Call to Action for community-wide intensification of a research enterprise in inquiries related to pediatric brain injury and motor disability by way of technological integration. But the barriers can seem high, and the pathways to integrative clinical research can seem poorly marked. Here, we answer the Call by providing framework to 3 objectives: (1) instrumentation, (2) biometrics and study design, and (3) data analytics. We identify emergent cases where this Call has been answered and advocate for others to echo the Call both in highly visible physical therapy venues and in forums where the audience is diverse.
Creative Dance Practice Improves Postural Control in a Child With Cerebral Palsy
Authors: Stribling Kate , Christy Jennifer
Published: September 2017

Purpose:

To investigate the effect of creative dance instruction on postural control and balance in an 11-year-old with spastic triplegic cerebral palsy, Gross Motor Function Classification Scale level II.

Descriptions:

We conducted 1-hour dance interventions twice weekly for 8 weeks, with a focus on somatosensory awareness and movement in all planes of motion. Computerized dynamic posturography using the SMART Balance Master/EquiTest (NeuroCom) was used to assess postural control and balance reactions before the first class and following the final class.

Outcomes:

Gains in standing stability, balance recovery, directional control, and endpoint excursion of movement were found. Participation in creative dance lessons appears to improve somatosensory effectiveness and postural control in a child with cerebral palsy.

What This Case Adds:

Dance is a fun way to improve balance and coordination. These interventions could be easily implemented into programs for children with cerebral palsy.
A Novel Mobility Device to Improve Walking for a Child With Cerebral Palsy
Authors: Fergus Andrea
Published: September 2017

Purpose:

To describe the use and outcomes associated with the Upsee in conjunction with Kinesiotape for a child with cerebral palsy.

Descriptions:

The Upsee and Kinesiotaping were implemented for 24 weeks with a 31-month-old child with cerebral palsy, Gross Motor Function Classification System level III.

Outcomes:

She progressed from walking with maximal assistance and extensive gait deviations to walking with supervision with a walker on level surfaces with improved gait. Genu recurvatum, heel strike, scissoring, hip extension, foot placement, step length, and stiff knee in swing improved on the basis of videotaped analyses. The Gross Motor Function Measure-66 improved by 11.4.

Conclusions and What This Case Adds:

The Upsee is a clinically feasible approach for gait impairments in children through providing increased opportunities for walking while supporting biomechanical alignment. Upsee effectiveness with and without taping is an area for future study.
Wide Linear Corticotomy and Anterior Segmental Osteotomy Under Local Anesthesia Combined Corticision for Correcting Severe Anterior Protrusion With Insufficient Alveolar Housing
Authors: Noh Min-Ki , Lee Baek-Soo , Kim Shin-Yeop , Jeon Hyeran Helen , Kim Seong-Hun , Nelson Gerald
Published: September 2017

Backgrounds:

This article presents an alternate surgical treatment method to correct a severe anterior protrusion in an adult patient with an extremely thin alveolus. To accomplish an effective and efficient anterior segmental retraction without periodontal complications, the authors performed, under local anesthesia, a wide linear corticotomy and corticision in the maxilla and an anterior segmental osteotomy in mandible.

Methods:

In the maxilla, a wide linear corticotomy was performed under local anesthesia. In the maxillary first premolar area, a wide section of cortical bone was removed. Retraction forces were applied buccolingually with the aid of temporary skeletal anchorage devices. Corticision was later performed to close residual extraction space. In the mandible, an anterior segmental osteotomy was performed and the first premolars were extracted under local anesthesia.

Results:

In the maxilla, a wide linear corticotomy facilitated a bony block movement with temporary skeletal anchorage devices, without complications. The remaining extraction space after the bony block movement was closed effectively, accelerated by corticision. In the mandible, anterior segmental retraction was facilitated by an anterior segmental osteotomy performed under local anesthesia. Corticision was later employed to accelerate individual tooth movements.

Conclusions:

A wide linear corticotomy and an anterior segmental osteotomy combined with corticision can be an effective and efficient alternative to conventional orthodontic treatment in the bialveolar protrusion patient with an extremely thin alveolar housing.
Dental Infection and Pregnancy: the Lack of Treatment by the Dental Professional Evolving to a Complex Maxillofacial Infection
Authors: Pereira Rodrigo dos Santos , Gomes-Ferreira Pedro Henrique Silva , Bonardi João Paulo , Silva Jonathan Ribeiro da , Latini Gustavo Lima , Hochuli-Vieira Eduardo
Published: September 2017

Infections of the maxillofacial complex caused by caries disease are common in dental practice. The professionals have to have technical knowledge to treat it at the onset of the condition and avoid the spread to deep anatomical spaces of face and neck, which can implicate in a risk of patients’ life.

In Brazil, current dental professionals usually denied oral surgical treatments in patients with some clinical conditions, not because of fear to resolve it but for lack of knowledge to treat it. An example of these conditionals is pregnancy. It is well known that during the pregnancy period, the patient can be treated in the correct period of gestation. Early diagnosis is crucial for effective therapy in serious infections. The treatment has to be crucial during pregnancy because of the potentially fatal situation that the disease can create to the pregnant woman and the fetus.

The aim of this article is to demonstrate a case of dental caries in a pregnant patient, which was evaluated by other professionals and had the treatment denied, evolving to a serious maxillofacial infection.
Lipoma on the Lower Lip
Authors: Aita Tiago Gai , Bonardi João Paulo , Stabile Gaykon Alex Vitti , Pereira-Stabile Cecilia Luiz , Faverani Leonardo Perez , Hochuli-Vieira Eduardo
Published: September 2017

Lipoma is a benign tumor of fat tissue, found frequently in subcutaneous tissues. However, oral manifestations are relatively rare. The present patient illustrates the successful treatment of a lipoma treated by complete excision of the lesion. A female patient, 75 years old, presenting lesion in the right oral vestibule where excisional biopsy was performed. The professional must diagnose this type of injury as soon as possible and treat it so that it does not take large proportions, which can result in esthetic and functional sequelae to the patient.
Effect of Facial Parameters in Primary Acquired Nasolacrimal Duct Obstruction
Authors: Vatansever Mustafa , Argin Mehmet Atila , Görür Kemal
Published: September 2017

Purpose:

In this study, the authors aimed to identify facial and nasal parameters, which may create an anatomic disposition toward obstruction in patients with primary acquired nasolacrimal duct obstruction.

Materials and Methods:

Forty-eight patients (14 males and 34 females) who presented to the ophthalmology outpatient clinic and were diagnosed with primary acquired nasolacrimal duct obstruction between January 2014 and January 2015 were included in the study. The control group comprised 59 patients (38 females and 21 males) without nasolacrimal duct obstruction. Measurements of nasal height, length, and depth, presence of a nasal hump, alar width and alar angle, distance between the maxillary bone nasal notches, and right and left distances between outer canthi and corners of the mouth were made using photographs of the patients. The presence of facial asymmetry was also assessed.

Results:

Facial asymmetry (P = 0.014) and nasal hump (P = 0.048) were more common in the patient group. The patient group had smaller nasal radix depth (P < 0.001), nasal length (P = 0.001), and alar width (P < 0.001), larger distance between maxillary bone nasal notches (P < 0.001), and smaller alar angle (P < 0.001).

Conclusion:

In the current study, the authors found that primary acquired nasolacrimal duct obstruction occurred more frequently on the side of the face with shorter facial measurements. Smaller nasal radix depth, nasal length, and alar base width, presence of a nasal hump and longer distance between maxillary bone nasal notches may form an anatomic basis for nasolacrimal duct obstruction. Based on our results, the authors believe that primary acquired nasolacrimal duct obstruction is associated with facial structure.
Levator Palpebrae Superioris Muscle Direct Neurotization
Authors: Cárdenas-Mejía Alexánder , Palafox Damián , Téllez-Palacios Daniela , Contreras-Merida Sara , Maza-Krzeptowsky Lilia de La , López Rubén , Hernández Tzilacatzin
Published: September 2017

Direct muscle neurotization has been proved to be a feasible technique for facial reanimation microsurgical procedures. Direct muscle neurotization is performed by implanting the interposition nerve graft directly into the substance of the muscle. The authors present the case of a 36-year-old male patient with upper eyelid dysfunction secondary to facial trauma. The levator palpebrae superioris muscle was macroscopically unaffected; however, neurophysiological test proved a selective denervation of the CN III motor branch to the levator palpebrae superioris muscle. Direct muscle neurotization was performed by means of 2 separate nerve procedures. The authors have made follow-up for 3 months after surgery. The authors have noted development of upper eyelid movement meaning adequate function of the neurotized muscle. The authors believe that this procedure could be integrated into the surgical options to treat selective nerve injuries should the right patient is encountered.
Complex Subunit Repair of a Cheek, Nose, and Medial Canthal Defect: A Stepwise Approach
Authors: Bhatt Mehul , Husain Zain , Tinklepaugh Adam Jon , Ciocon David Hermogenes
Published: September 2017

A recent national survey suggests that up to one-third of facial reconstructive and plastic surgeons do not adhere to the classical principle of subunit reconstruction. While single-stage flaps and grafts may be easier and less time consuming, they can also lead to a poor cosmetic outcome. Here, the authors describe how the authors repaired a complex post-Mohs surgery facial defect involving multiple cosmetic subunits and how adherence to the subunit principle was essential to obtaining the most optimal functional and esthetic outcome.
An Effective Technique for Nasal Radix Reduction in Septorhinoplasty: Procerus Muscle Resection
Authors: Kayabaşoğlu Gürkan , Dizdar Denizhan
Published: September 2017

In rhinoplasty patients radix position profoundly impacts the appearance of the nasal profile by influencing dorsal length, contour, angulation, and height. The authors wanted to introduce a new perspective to radix, and decided to focus on subcutaneous tissues, especially procerus muscle. Actually resection of procerus and corrugator supercilii is a part of browlift and endoscopic facelift techniques, with which the authors are already familiar.

In this short report and video, the authors wanted to present a new technique to lower radix area. This technique is based on face anatomy, and muscles under radix area, and takes its roots from facelift techniques. Before introducing the authors’ technique the authors wanted to show the effect of soft tissues on radix with lateral nasal x-rays. With this maneuver the soft tissue thickness of radix area is thinned.
Pediatric Orbital Floor Fractures: Clinical and Radiological Predictors of Tissue Entrapment and the Effect of Operative Timing on Ocular Outcomes
Authors: Firriolo Joseph M. , Ontiveros Nicole C. , Pike Carolyn M. , Taghinia Amir H. , Rogers-Vizena Carolyn R. , Ganor Oren , Greene Arin K. , Meara John G. , Labow Brian I.
Published: September 2017

Orbital floor fractures can produce acute constitutional symptoms and poor ocular outcomes. This study aims to determine the clinical and radiological predictors of tissue entrapment in pediatric orbital floor fractures and to explore the effect of operative timing on ocular outcomes. The authors reviewed medical records from pediatric patients with orbital floor fractures from 2007 to 2015. One hundred fifty-two patients with 159 orbital floor fractures were included. One hundred twenty-two (80.3%) patients were male, and the mean age was 12.2 years. Twelve patients sustained orbital floor fractures with tissue entrapment. At presentation extraocular movement (EOM) restriction, diplopia, nausea, and vomiting were all associated with tissue entrapment (P < 0.001). Among patients with trapdoor fractures (determined by facial computed tomography), the presence of nausea and/or vomiting was predictive of tissue entrapment: positive predictive value 80%, negative predictive value 100%. For all the patients, regardless of fracture configuration, the presence of nausea and/or vomiting was valuable in ruling out tissue entrapment: sensitivity 83.3%, negative predictive value 98.1%. In tissue entrapment patients, poorer ocular outcomes (EOM restriction and diplopia) were associated with the length of operation (P = 0.007), but not the time interval to operation (P = 0.146). The authors conclude that nausea and vomiting are valuable predictors of tissues entrapment, particularly when EOM restriction and diplopia are equivocal. In the authors’ study, radiological findings were also predictive of entrapment, but inconsistent language in this area limits the external validity of these results. The authors’ study draws attention to the relationship between operation length and poorer ocular outcomes, suggesting that case severity/complexity and surgeon technique/experience may influence outcomes.
Autologous Tissue Graft in Revision Medial Epicanthoplasty Using Subciliary Fat and Orbicularis Oculi Muscle
Authors: Kim Jeenam , Kim Junyeong , Kim Jungil , Shin Donghyeok , Lee Myungchul , Choi Hyungon
Published: September 2017

The medial epicanthal fold is one of the racial anatomic characteristics of Asians. As medial epicanthoplasty has become one of the most common cosmetic surgeries among Asians, the need for revision of overcorrected medial epicanthus also increased. In revision medial epicanthoplasty, an autologous tissue graft to the subcutaneous plane is used to reduce postoperative scar. Medial epicanthoplasty, using V–Y advancement and rotation flap, was performed in 93 patients (revision medial epicanthoplasty with autologous tissue graft, 60 patients; revision medial epicanthoplasty only, 33 patients). A V–Y and rotation flap was designed to cover the overexposed lacrimal lake. A small amount of fat tissue and orbicularis oculi muscle were harvested from the upper eyelid through the double-fold line and grafted to the subcutaneous space of the medial epicanthal area. We evaluated the patients’ satisfaction with the overall outcome and scar. The mean intercanthal distance increased from 32.3 mm before surgery to 34.6 mm after surgery. Satisfaction with the scar and overall outcome was higher in the patient group who underwent medial epicanthoplasty with autologous tissue graft. No complication was observed in the autologous tissue graft group, whereas 1 patient who underwent medial epicanthoplasty without autologous tissue graft showed recurrence of the medial epicanthal fold, 5 months after surgery. Medial epicanthoplasty with autologous tissue graft is a simple and reliable method to repair the overcorrected medial epicanthus that can efficiently increase the intercanthal distance and prevent scar contracture.
Associations Between Type and Route of Hormone Use on Urinary Incontinence and Pelvic Organ Prolapse in Premenopausal and Postmenopausal Women
Authors: Cardenas-Trowers Olivia Orlinda , Borgstrom Mark , Addis Ilana
Published: September 2017

Objective

The aim of this study was to evaluate the associations between type and route of hormone use and urinary incontinence (UI) and pelvic organ prolapse (POP) in premenopausal and postmenopausal women.

Methods

The authors used the National Health and Nutritional Examination Survey database for data from 2005–2006, 2007–2008, 2009–2010, and 2011–2012. Seven thousand sixty-six of the women included were premenopausal, and 5387 were postmenopausal. Premenopausal women were younger than 51 years and reported menstrual periods in the last 12 months. Postmenopausal women reported being in natural or surgical menopause. Urinary incontinence was defined as experiencing urinary leakage “less than once a month” or more. Pelvic organ prolapse was defined as an affirmative response to “experience bulging in the vaginal area.” Hormone route and use were stratified in years. Pearson χ2 and Pearson correlations were used, with P < 0.05 considered significant.

Results

In premenopausal women, birth control pills, estrogen/progestin pills, and estrogen-only patch use are associated with UI (P < 0.05). Birth control pills are associated with both UI and POP in premenopausal women (P < 0.05 for UI and POP). In postmenopausal women, estrogen-only pills, and estrogen/progestin pill use are associated with UI (P < 0.05). Birth control pill use is associated with POP in postmenopausal women (P = 0.029). Neither estrogen patch nor estrogen/progestin patch is associated with UI or POP in postmenopausal women.

Conclusions

Type and route of hormone use have varied associations with UI and POP in premenopausal and postmenopausal women. Prospective studies are needed to further evaluate the effect of hormone type and route on UI and POP in premenopausal and postmenopausal women.
Structural aspects of the inactive X chromosome
Authors: Bonora Giancarlo , Disteche Christine M.
Published: September 2017

A striking difference between male and female nuclei was recognized early on by the presence of a condensed chromatin body only in female cells. Mary Lyon proposed that X inactivation or silencing of one X chromosome at random in females caused this structural difference. Subsequent studies have shown that the inactive X chromosome (Xi) does indeed have a very distinctive structure compared to its active counterpart and all autosomes in female mammals. In this review, we will recap the discovery of this fascinating biological phenomenon and seminal studies in the field. We will summarize imaging studies using traditional microscopy and super-resolution technology, which revealed uneven compaction of the Xi. We will then discuss recent findings based on high-throughput sequencing techniques, which uncovered the distinct three-dimensional bipartite configuration of the Xi and the role of specific long non-coding RNAs in eliciting and maintaining this structure. The relative position of specific genomic elements, including genes that escape X inactivation, repeat elements and chromatin features, will be reviewed. Finally, we will discuss the position of the Xi, either near the nuclear periphery or the nucleolus, and the elements implicated in this positioning.

This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.
X chromosome inactivation in a female carrier of a 1.28 Mb deletion encompassing the human X inactivation centre
Authors: de Hoon B. , Splinter Erik , Eussen B. , Douben J. C. W. , Rentmeester E. , van de Heijning M. , Laven J. S. E. , de Klein J. E. M. M. , Liebelt J. , Gribnau J.
Published: September 2017

X chromosome inactivation (XCI) is a mechanism specifically initiated in female cells to silence one X chromosome, thereby equalizing the dose of X-linked gene products between male and female cells. XCI is regulated by a locus on the X chromosome termed the X-inactivation centre (XIC). Located within the XIC is
XIST
, which acts as a master regulator of XCI. During XCI,
XIST
is upregulated on the inactive X chromosome and chromosome-wide
cis
spreading of
XIST
leads to inactivation. In mouse, the Xic comprises
Xist
and all
cis
-regulatory elements and genes involved in
Xist
regulation. The activity of the XIC is regulated by
trans
-acting factors located elsewhere in the genome: X-encoded XCI activators positively regulating XCI, and autosomally encoded XCI inhibitors providing the threshold for XCI initiation. Whether human XCI is regulated through a similar mechanism, involving
trans
-regulatory factors acting on the XIC has remained elusive so far. Here, we describe a female individual with ovarian dysgenesis and a small X chromosomal deletion of the XIC. SNP-array and targeted locus amplification (TLA) analysis defined the deletion to a 1.28 megabase region, including
XIST
and all elements and genes that perform
cis
-regulatory functions in mouse XCI. Cells carrying this deletion still initiate XCI on the unaffected X chromosome, indicating that XCI can be initiated in the presence of only one XIC. Our results indicate that the
trans
-acting factors required for XCI initiation are located outside the deletion, providing evidence that the regulatory mechanisms of XCI are conserved between mouse and human.

This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.
Prasinovirus attack of Ostreococcus is furtive by day but savage by night
Authors: Derelle Evelyne , Yau Sheree , Moreau Hervé , Grimsley Nigel H.
Published: September 2017

Prasinoviruses are large DNA viruses that infect diverse genera of green microalgae worldwide in aquatic ecosystems, but molecular knowledge of their life-cycles is lacking. Several complete genomes of both these viruses and their marine algal hosts are now available and have been used to show the pervasive presence of these species in microbial metagenomes. We have analysed the life-cycle of OtV5, a lytic virus, using RNA-Seq from 12 time points of healthy or infected Ostreococcus tauri cells over a day/night cycle in culture. In the day, viral gene transcription remained low while host nitrogen metabolism gene transcription was initially strongly repressed for two successive time points before being induced for 8 hours, but in the night viral transcription increased steeply while host nitrogen metabolism genes were repressed and many host functions that are normally reduced in the night appeared to be compensated either by genes expressed from the virus or by increased expression of a subset of 4.4 % of the host’s genes. Some host cells lysed progressively during the night, but a larger proportion lysed the following morning. Our data suggest that the life-cycles of algal viruses mirror the diurnal rhythms of their hosts.
Differential Impacts of Dietary Modification on Individual Metabolic Phenotypes and their Relationship to Blood Pressure: Evidence of Latent Dietary Responder Sub-phenotypes
Authors: Loo Ruey Leng , Zou Xin , Appel Lawrence J , Nicholson Jeremy K. , Holmes Elaine
Published: September 2017

Background

Hypertension is a worldwide public health issue with significant comorbidity and mortality. We aimed to identify urinary metabolic phenotypes associated with three healthy diets and to establish their relationship to blood pressure (BP).

Methods and Results

—24-h urine samples from 158 participants, with pre-hypertension and hypertension, consumed a carbohydrate-rich, a protein-rich and a monounsaturated fat-rich healthy diet (6-week per diet) in randomized order, were analyzed by nuclear magnetic resonance spectroscopy. Combinations of metabolites significantly associated with each diet were identified, and associations between these metabolites and cardiovascular disease risk were established. We found coherent responses to all three diets including increased excretion of metabolites originating from vegetables/fruits, protein, tryptophan metabolism and gut microbial-mammalian co-metabolism. Proline betaine (marker of citrus fruit) was significantly inversely associated with systolic BP; 4-cresyl sulfate (gut microbial metabolite) inversely correlated with both systolic and diastolic BP; and hippurate (gut microbial metabolite) - directly associated with reduced systolic BP.

Conclusions

Variation in metabolic phenotypes in response to specific diets may hold clues as to the mechanisms underlying inter-individual differences in dietary response. Stratification of individuals based on diet-specific urinary phenotypes highlights the feasibility for individualized approaches to dietary therapy for lowering BP.

Clinical Trial Registration

This intervention study is registered athttp://www.clinicaltrials.govasNCT00051350
An automated model test system for systematic development and improvement of gene expression models
Authors: Reis Alexander C. , Salis Howard M.
Published: September 2017

Gene expression models greatly accelerate the engineering of synthetic metabolic pathways and genetic circuits by predicting sequence-function relationships and reducing trial-and-error experimentation. However, developing models with more accurate predictions is a significant challenge, even though they are essential to engineering complex genetic systems. Here we present a model test system that combines advanced statistics, machine learning, and a database of 9862 characterized genetic systems to automatically quantify model accuracies, accept or reject mechanistic hypotheses, and identify areas for model improvement. We also introduce Model Capacity, a new information theoretic metric that enables correct model comparisons across datasets. We demonstrate the model test system by comparing six models of translation initiation rate, evaluating 100 mechanistic hypotheses, and uncovering new sequence determinants that control protein expression levels. We applied these results to develop a biophysical model of translation initiation rate with significant improvements in accuracy. Automated model test systems will dramatically accelerate the development of gene expression models, and thereby transition synthetic biology into a mature engineering discipline.
An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components
Authors: Sharp Nathaniel P. , Agrawal Aneil F.
Published: September 2017

Despite decades of research, the factors that maintain genetic variation for fitness are poorly understood. Mutation selection balance will always contribute to standing variance, but it is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to mutation-selection balance can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the actual standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the mutation-selection balance model, and could be used to identify traits or populations where genetic variance is maintained by factors beyond mutation-selection balance. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. To encourage the application of this approach, we describe the underlying theory and use it to test the mutation selection balance model for three traits inDrosophila melanogaster. We find some evidence for non-mutational variance in male mating success and female fecundity relative to larval viability, which is consistent with balancing selection on sexual fitness components. Finally, we discuss the theoretical and practical limitations to this approach, and discuss how to apply it successfully.
High concentrations of boric acid induce autophagy in cancer cell lines
Authors: Al-Ali Ruslan , Gonzalez-Sarmiento Rogelio
Published: September 2017

Background/Aim

Boric acid (BA) is thought to have anticancer effects, but only a handful of studies tackled this subject. Though a very common compound, little is known about its therapeutic value, mechanisms and effective doses. This study investigates into its therapeutic value and autophagy as a possible mechanism.

Materials and Methods

We evaluated the potency of BA treatment in seven different cell lines. We hypothesized that autophagy is involved in the mechanism of BA toxicity in tumor cells based on observations in plants, insects and cancer cell lines. Changes in autophagy-related proteins were measured after BA treatment. Finally, we suspected that blockage of autophagy would increase the effectiveness of BA treatment and enable the use of smaller doses.

Results

Our results demonstrate that all studied cell lines did not suffer mortality in low to medium doses of BA (up to 5mM). However, a high dose (over 25mM) could inflict significant death in all cell lines. Those high doses caused P62/SQSTM1 consumption and LC3II-B accumulation after 3 days of treatment. Using small doses of BA in combination with autophagy blockage did not improve cytotoxicity in lung cancer cell lines.

Conclusion

We conclude that high concentrations of BA affect autophagy in short-term treatments. Not enough data is available about BA toxicity, so BA use as cancer treatment can be possible if new toxicity studies are performed.
CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles
Authors: Lemos Brenda R. , Kaplan Adam C. , Bae Ji Eun , Ferazzoli Alex , Kuo James , Anand Ranjith P. , Waterman David P. , Haber James E.
Published: September 2017

Harnessing CRISPR-Cas9 technology has provided an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We have analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in the budding yeastSaccharomyces cerevisiaeand find that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a one base pair (+1) insertion that appears to result from Cas9 creating a 1-bp 5’ overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which were biased toward homonucleotide insertions. Using inverted PAM (iPAM) sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9::gRNA complex influences subsequent NHEJ processing. As with well-studied events induced by the site-specific HO endonuclease, CRISPR-Cas9 mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events, however, are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11’s nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells (van Overbeek et al., 2016) reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.
Architecture of mammalian centriole distal appendages accommodates distinct blade and matrix functional elements
Authors: Yang T. Tony , Chong Weng Man , Wang Won-Jing , Mazo Gregory , Tanos Barbara , Chen Zhengmin , Nguyet Tran Thi Minh , Chen Yi-De , Weng Rueyhung Roc , Huang Chia-En , Jane Wann-Neng , Tsou Meng-Fu Bryan , Liao Jung-Chi
Published: September 2017

Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here, we determined a superresolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we termed the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164 which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.
Antibodies set boundaries limiting microbial metabolite penetration and the resultant mammalian host response
Authors: Uchimura Yasuhiro , Fuhrer Tobias , Li Hai , Lawson Melissa A. , Zimmermann Michael , Gomez de Agüero Mercedes , Yilmaz Bahtiyar , Ronchi Francesca , Sorribas Marcel , Hapfelmeier Siegfried , Ganal-Vonarburg Stephanie C. , McCoy Kathy D. , Sauer Uwe , Macpherson Andrew J.
Published: September 2017

Although the mammalian microbiota is well-contained within the intestine and on other body surfaces, it profoundly shapes development and metabolism of almost every host organ, presumably through pervasive microbial metabolite penetration. The challenge is that most metabolites can be of both host and microbial origin. We developed a model to distinguish between microbial and host metabolites by stable isotope tracing using fully13C-labelled live non-replicatingEscherichia coli, differentiating12C and13C isotopes with high-resolution mass spectrometry. Hundreds of microbial compounds penetrated across 23 host tissues and fluids after intestinal exposure: subsequent12C host metabolome signatures included lipidemia, reduced glycolysis and inflammation. Mucosal barrier maturation with transient microbial exposure increased early clearance of penetrant bacterial metabolites from the small intestine into the urine, independently of antibody induction. Induced antibodies curtailed microbial metabolite exposure at the intestinal surface, by accelerating intestinal bacterial transit into the colon where metabolite transport mechanisms are limiting.
Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors
Authors: Zhu Yanan , Ramasawmy Rajiv , Johnson Sean Peter , Taylor Valerie , Gibb Alasdair , Pedley R Barbara , Chattopadhyay Nibedita , Lythgoe Mark F , Golay Xavier , Bradley Daniel , Walker-Samuel Simon
Published: September 2017

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.
Continuous rearrangement of the postsynaptic gephyrin scaffolding domain: a super-resolution quantified and energetic approach
Authors: Rodriguez Pamela C. , Almeida Leandro G. , Triller Antoine
Published: September 2017

Synaptic function and plasticity requires a delicate balance between overall structural stability and the continuous rearrangement of the components that make up the presynaptic active zone and the postsynaptic density (PSD). Photoactivated localization microscopy (PALM) has provided a detailed view of the nanoscopic structure and organization of some of these synaptic elements. Still lacking, are tools to address the morphing and stability of such complexes at super-resolution. We describe an approach to quantify morphological changes and energetic states of multimolecular assemblies over time. With this method, we studied the scaffold protein gephyrin, which forms postsynaptic clusters that play a key role in the stabilization of receptors at inhibitory synapses. Postsynaptic gephyrin clusters exhibit an internal microstructure composed of nanodomains. We found, that within the PSD, gephyrin molecules continuously undergo spatial reorganization. This dynamic behavior depends on neuronal activity and cytoskeleton integrity. The proposed approach also allowed access to the effective energy responsible for the tenacity of the PSD despite molecular instability.

Significant statement

Super-resolution microscopy has become an important tool for the study of biological systems, allowing detailed, nano-scale structural reconstruction, single molecule tracking, particle counting, and interaction studies. However, quantification tools that take full advantage of the information provided by this technology are still lacking. We describe a novel quantification method to obtain information related to the size, directionality, dynamics, and stability of clustered structures from super-resolution microscopy. With this method, we studied the stability of gephyrin clusters, the main inhibitory scaffold protein. We found that gephyrin molecules continuously undergo reorganization based on neuronal activity and changes in the cytoskeleton.