bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Paediatric Ulcerative Colitis, Part 1
Authors: Turner Dan , Ruemmele Frank M. , Orlanski‐Meyer Esther , Griffiths Anne M. , de Carpi Javier Martin , Bronsky Jiri , Veres Gabor , Aloi Marina , Strisciuglio Caterina , Braegger Christian P. , Assa Amit , Romano Claudio , Hussey Séamus , Stanton Michael , Pakarinen Mikko , de Ridder Lissy , Katsanos Konstantinos , Croft Nick , Navas‐López Victor , Wilson David C. , Lawrence Sally , Russell Richard K.
Published: May 2018

Background:

The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ~20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)‐unclassified through detailed recommendations and practice points.

Methods:

These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face‐to‐face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate.

Results:

These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision‐making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD‐classes criteria and IBD‐unclassified is also part of these guidelines.

Conclusions:

These guidelines provide a guide to clinicians managing children with UC and IBD‐unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
Central Venous Catheter–associated Venous Thromboembolism in Children With Hematologic Malignancy
Authors: Onyeama Sara-Jane N. , Hanson Sheila J. , Dasgupta Mahua , Baker Kathryn , Simpson Pippa M. , Punzalan Rowena C.
Published: May 2018

In pediatric oncology, the diagnosis of a hematologic malignancy and presence of a central venous catheter (CVC) have been identified as significant risk factors for the development of a venous thromboembolism (VTE). There remain little data regarding CVC factors associated with CVC-related VTE. Using the VTE and oncology database in a quaternary care center, a retrospective cohort study was conducted in children below 18 years old with hematologic cancer from November 5, 2012 to April 4, 2016. Patient, CVC factors, and VTE occurrence were analyzed to identify significant patient and CVC factors associated with the development of clinically identified CVC-related VTE. Utilizing the χ2, Mann-Whitney, and the Fisher exact tests, patient factors were compared across VTE yes/no groups. Of the 198 study patients, 22 VTE cases were identified. Eighteen VTE events were CVC-associated, occurring in 9% of study population. Peripherally inserted central catheter lines and older ages were associated with VTE. The use of tissue-plasminogen activator for CVC occlusion was associated with decreased VTE rates, suggesting a protective potential.
Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Authors: Winer Lindsey , Macedo Francisco I. , Alfawaz Abdullah , Sommariva Antonio , Cecchetto Giovanni , Podda Antonello , Neville Holly L. , Möller Mecker G.
Published: May 2018

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population.
Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions
Authors: Borra Tiziana , Custrin Ana , Saggini Andrea , Fink-Puches Regina , Cota Carlo , Vermi William , Facchetti Fabio , Cerroni Lorenzo
Published: May 2018

Pityriasis lichenoides (PLs) is an uncommon skin disease of unknown etiology. In recent years, an atypical form of PL has been described, showing overlapping features with mycosis fungoides (MF) and lymphomatoid papulosis. We studied 66 patients with an initial histopathologic diagnosis of PL (M:F=34:32; median age, 25 y; range, 7 to 85 y). According to clinical and phenotypic features, cases were classified into 4 categories: (1) Conventional PL (characteristic clinical features of PL without phenotypic aberrations) (n=20; M:F=8:12; median age, 37 y; range, 9 to 74 y); (2) Atypical form of PL (characteristic clinical features of PL with phenotypic aberrations) (n=25; M:F=16:9; median age, 21 y; range, 7 to 72 y). Four of these patients subsequently developed MF; (3) Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30) (n=10; M:F=4:6; median age, 41 y; range, 16 to 83 y); (4) MF (clinical features typical of MF) (n=11; M:F=6:5; median age, 17 y; range, 8 to 85 y). Molecular analyses of clonality of the infiltrate did not reveal relevant differences among these 4 groups. Our study suggests that patients with an initial histopathologic diagnosis of PL may belong to different groups, showing that clinicopathologic correlation and complete phenotypic analyses are paramount in order to achieve proper classification. Although the relationship between PL and MF is yet a matter of debate, at the present state of knowledge, patients with a clinicopathologic presentation consistent with PL but with aberrant phenotypic features should be monitored in order to detect a possible evolution into MF.
Physicians' Risk Tolerance and Head Computed Tomography Use for Pediatric Patients With Minor Head Injury
Authors: Cheng Chi-Yung , Pan Hsiu-Yung , Li Chao-Jui , Chen Yi-Chuan , Chen Chien-Chih , Huang Yi-Syun , Cheng Fu-Jen
Published: May 2018

Objectives

Traumatic brain injury is the leading cause of death and disability in children worldwide. The objective of this study was to determine the association between physician risk tolerance and head computed tomography (CT) use in patients with minor head injury (MHI) in the emergency department (ED).

Methods

We retrospectively analyzed pediatric patients (<17 years old) with MHI in the ED and then administered 2 questionnaires (a risk-taking subscale [RTS] of the Jackson Personality Inventory and a malpractice fear scale [MFS]) to attending physicians who had evaluated these patients and made decisions regarding head CT use. The primary outcome was head CT use during ED evaluation; the secondary outcome was ED length of stay and final diagnosis of intracranial injury (ICI).

Results

Of 523 patients with MHI, 233 (44.6%) underwent brain CT, and 16 (3.1%) received a final diagnosis of ICI. Among the 16 emergency physicians (EPs), the median scores of the MFS and RTS were 22 (interquartile range, 17–26) and 23 (interquartile range, 19–25), respectively. Emergency physicians who were most risk averse tended to order more head CT scans compared with the more risk-tolerant EPs (56.96% vs 37.37%; odds ratio, 8.463; confidence interval, 2.783–25.736). The ED length of stay (P = 0.442 and P = 0.889) and final diagnosis (P = 0.155 and P = 0.835) of ICI were not significantly associated with the RTS and MFS scores.

Conclusions

Individual EP risk tolerance, as measured by RTS, was predictive of CT use in pediatric patients with MHI.
Papilloma of the Fallopian Tube: A Rare Gynecologic Neoplasm Harboring a BRAF (c.1799T>A) Mutation (V600E)
Authors: Wohlschlaeger Jeremias , Davidson Ben , Worm Karl , Feist Henning , Peters Jochen , Hager Thomas , Schmid Kurt W. , Ostertag Horst
Published: May 2018

Papillomas of the fallopian tube are exceedingly rare benign tumors, and only very few cases have been reported in the literature. Clinically, they may present as a mass lesion or occur without symptoms. Histomorphologically, they are papillary tumors covered by nonatypical epithelium with occasional ciliated or goblet cells growing in the lumen, and they are most frequently located in the infundibular region of the fallopian tube. They require a number of differential diagnostic evaluations and can be mistaken for either other benign tumors or malignant neoplasms. Because of their rare occurrence, molecular data about this entity have been lacking so far. Herein, a case of a papilloma with a BRAF (c.1799T>A) mutation (V600E) in a 45-yr-old woman with tumor-like dilation of the fallopian tube is presented.
Fascin as a Useful Marker for Identifying Neural Components in Immature Teratomas of Human Ovary and Those Derived From Murine Embryonic Stem Cells
Authors: Umehara Ryunosuke , Kurata Atsushi , Takanashi Masakatsu , Hashimoto Hirotsugu , Fujita Koji , Nagao Toshitaka , Kuroda Masahiko
Published: May 2018

Immature teratoma of the human ovary is a rare disease, and its diagnosis and grading are currently based on histologic evaluation of the presence and amount of immature neural components in the tumor. Despite the importance of tumor grading, immature neural components especially without rosette formation are difficult to identify, partly because useful biomarkers for them are not yet available. Toward this goal, we investigated 16 immature teratomas from human ovaries as well as 10 of those derived from murine embryonic stem cells transplanted into immunodeficient mice. Immunohistochemistry was performed for cytokeratin, glial fibrillary acidic protein, S100, and fascin. It was demonstrated that glial fibrillary acidic protein and S100 expression was not observed in the immature neural components of immature teratomas derived from both human ovary and embryonic stem cells, although their expression was detected in mature neural tissues. In contrast, fascin immunopositivity was clearly found in both mature and immature neural components regardless of rosette formation in immature teratomas derived from both human ovary and embryonic stem cells. Assessment of immature neural components by fascin immunostaining yielded the same or slightly increased quantity than quantification based on hematoxylin and eosin staining. These results suggest that fascin immunostaining is useful as a biomarker in correctly diagnosing and grading human immature teratomas. Further, fascin immunostaining may contribute to the development of regenerative medicine through accurate assessment of the maturation status of pluripotent stem cell-derived tumors transplanted into immunodeficient mice.
Fatigue After Aneurysmal Subarachnoid Hemorrhage Is Highly Prevalent in the First-Year Postonset and Related to Low Physical Fitness
Authors: Harmsen Wouter J. , Ribbers Gerard M. , Heijenbrok-Kal Majanka H. , Khajeh Ladbon , Sneekes Emiel M. , van Kooten Fop , Neggers Sebastian J.C.M.M. , van den Berg-Emons Rita J.
Published: May 2018

Objective

The aim of the study was to investigate whether low physical fitness and inactive and sedentary lifestyles play a role in the severity of fatigue in patients with aneurysmal subarachnoid hemorrhage (a-SAH).

Design

This is a prospective 1-yr follow-up study, including a total of 52 patients with a-SAH. Outcome measures included the Fatigue Severity Scale score, peak oxygen uptake (VO2peak), isokinetic knee muscle strength (peak torque), physical activity (% 24-hr period), and sedentary behavior (% waking hours) and were evaluated at 6 and 12 mos after onset.

Results

Fatigue was highly prevalent in the first year and reported by 48% of the patients at 6 mos and by 52% at 12 mos after a-SAH. Fatigue was associated with the knee extension (P < 0.001) and flexion strength (P < 0.001). A nonsignificant trend for a relationship was found between fatigue and the aerobic capacity (P = 0.079). No relationships were found between fatigue and physical activity or sedentary behavior. Fatigue could not be predicted by disease-related characteristics.

Conclusions

Half of the patients were fatigued in the first year after a-SAH. Interventions are necessary to reduce fatigue and should consider exercise training as a potential contributor to a multimodal treatment, preventing debilitating conditions after a-SAH.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Upon completion of this article, the reader should be able to: (1) Recognize the association between fatigue and physical fitness in patients after aneurysmal subarachnoid hemorrhage; (2) Determine the severity of fatigue complaints in patient after aneurysmal subarachnoid hemorrhage; and (3) Discuss the role of physical deconditioning in the management of fatigue in patients after aneurysmal subarachnoid hemorrhage.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Influence of Creatine Supplementation on Apoptosis Markers After Downhill Running in Middle-Aged Men
Authors: Sheikholeslami-Vatani Dariush , Faraji Hassan
Published: May 2018

Objective

Strenuous exercise can induce apoptosis in a variety of tissues. We investigated the effects of creatine loading on apoptosis markers after downhill running.

Design

Twenty-two middle-aged men were randomly assigned to either a creatine or a placebo group. Crossover design, double-blind controlled supplementation was performed using 20 g/d−1 of creatine or maltodextrin for 7 days. Downhill running (12% incline) at 70% of heart rate maximum for 40 mins was performed on the eighth day. Blood samples were taken on the day before supplementation, after supplementation and after running.

Results

There were no significant changes in the caspase-3, caspase-9, p53, Bax, and IGF-1 concentrations from presupplementation to postsupplementation in both groups of creatine and placebo (P > 0.05). There were significant increases (P < 0.05) in serum caspase-3, caspase-9, p53, and Bax after running in the placebo group. These markers were not noticeably changed in the creatine group (P > 0.05). Bcl-2 was unchanged in the placebo group but substantially increased (P < 0.05) in the creatine group. No significant changes were observed in IGF-1 concentration after running comparing to prerunning in both groups (P > 0.05). Lactate levels increased similarly in both groups (P < 0.05).

Conclusions

The findings indicate that creatine supplementation could prevent exercise-induced apoptotic markers.
HIV Pre-Exposure Prophylaxis Stigma as a Multidimensional Barrier to Uptake Among Women Who Attend Planned Parenthood
Authors: Calabrese Sarah K. , Dovidio John F. , Tekeste Mehrit , Taggart Tamara , Galvao Rachel W. , Safon Cara B. , Willie Tiara C. , Caldwell Abigail , Kaplan Clair , Kershaw Trace S.
Published: May 2018

Background:

Pre-exposure prophylaxis (PrEP) uptake has lagged among US women. PrEP stigma is a recognized barrier to uptake among men who have sex with men but remains largely unexplored among women. This study examined the pervasiveness of PrEP stigma among US women and its implications for uptake.

Setting/Methods:

In a 2017 online survey of Planned Parenthood patients drawn from the 3 cities with the highest numbers of new HIV infections in Connecticut, 597 heterosexually active, HIV-negative, PrEP-inexperienced women reported background characteristics, 2 dimensions of anticipated PrEP stigma (PrEP-user stereotypes and PrEP disapproval by others), and 3 indicators of potential PrEP uptake (interest in learning more about PrEP, intention to use PrEP, and comfort discussing PrEP with a provider).

Results:

Participants commonly perceived PrEP-user stereotypes, with many believing that others would regard them as promiscuous (37%), HIV-positive (32%), bad (14%), or gay (11%) if they used PrEP. Thirty percent would feel ashamed to disclose PrEP use. Many participants expected disapproval by family (36%), sex partners (34%), and friends (25%). In adjusted analyses, perception of PrEP-user stereotypes was uniquely associated with less comfort discussing PrEP with a provider. Expected PrEP disapproval by others was uniquely associated with less PrEP interest, less intention to use PrEP, and less comfort discussing PrEP with a provider. Exploratory moderation analyses suggested that intention to use PrEP was greatest when participants anticipated low levels of both PrEP-user stereotypes and PrEP disapproval by others.

Conclusions:

Findings highlight the need for positive messaging targeting potential PrEP users and their social networks to increase PrEP acceptance and uptake.
Differences in Cognitive Function Between Women and Men With HIV
Authors: Maki Pauline M. , Rubin Leah H. , Springer Gayle , Seaberg Eric C. , Sacktor Ned , Miller Eric N. , Valcour Victor , Young Mary A. , Becker James T. , Martin Eileen M. ,   for the Neuropsychology Working Groups of the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study
Published: May 2018

Background:

Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic, lifestyle, mental health, and biological factors. However, studies to date have yielded inconsistent findings on the existence, magnitude, and pattern of sex differences. We examined these issues using longitudinal data from 2 large, prospective, multisite, observational studies of US women and men with and without HIV.

Setting:

The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS).

Methods:

HIV-infected (HIV+) and uninfected (HIV−) participants in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed, executive function, and fine motor skills. Groups were matched on HIV status, sex, age, education, and black race. Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores. Results were adjusted for other confounding factors.

Results:

The sample (n = 1420) included 710 women (429 HIV+) and 710 men (429 HIV+) (67% non-Hispanic black; 53% high school or less). For continuous T-scores, sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B, Grooved Pegboard, and Symbol Digit Modalities Test. For these tests, HIV+ women scored lower than HIV+ men, with no sex differences in HIV− individuals. In analyses of categorical scores, particularly the Trail Making Test part A and Grooved Pegboard nondominant, HIV+ women also had a higher odds of impairment compared with HIV+ men. Sex differences were constant over time.

Conclusions:

Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages. Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions.
Influence of Gadolinium-Based Contrast Agents on Tissue Sodium Quantification in Sodium Magnetic Resonance Imaging
Authors: Paschke Nadia Karina , Neumann Wiebke , Uhrig Tanja , Winkler Manuel , Neumaier-Probst Eva , Fatar Marc , Schad Lothar Rudi , Zöllner Frank Gerrit
Published: May 2018

Objectives

Sodium magnetic resonance (MR) imaging provides noninvasive insights to cellular processes by measuring tissue sodium concentration (TSC). Many clinical studies combine sodium MR imaging with clinical standard MR procedures, in which contrast media is frequently administered. This work investigates the influence of gadolinium-based contrast agents on quantification of TSC. Thus, either scan pauses between early and late contrast-enhanced acquisitions can be used efficiently or sodium imaging can be performed as the final scan after dynamic contrast-enhanced acquisition.

Materials and Methods

For this study, 2 gadolinium-based contrast agents, Dotarem and Gadovist, were diluted with saline solution covering contrast agent concentrations in a clinical range. In addition, agarose-based sample series were created to simulate tissue relaxation time behavior. In vivo, the influence of Dotarem on sodium acquisition and TSC quantification was investigated in 1 ischemic stroke patient.

Results

Proton relaxation times decreased for increasing contrast agent concentrations as hyperbolic functions. Sodium relaxation times displayed a negative slope in regression analysis in most cases. The largest influence (−1.52 milliseconds per mmol/L contrast agent) was measured for sodium T1. Worst case calculations in ultrashort echo time sequence signal analysis showed a signal drop of (1.21% ± 0.56%) on tissue sodium quantification. In vivo sodium brain acquisitions of a stroke patient before and after Dotarem injection resulted in statistically nonsignificant differences in TSC quantification of relevant tissues and stroke areas (P > 0.05).

Conclusions

Our study showed a quantitative influence of Dotarem and Gadovist on sodium relaxation times. However, quantification of TSC was not impaired, which was proven by worst case calculations and nonsignificant differences in vivo in an ischemic stroke patient. We suggest performing sodium imaging in useful clinical positions in protocols regardless of included Dotarem or Gadovist administrations. Being flexible in the study protocol design will strengthen ongoing sodium imaging investigations for various pathologies.
Anatomic Study of Craniocervical Junction and Its Surrounding Structures in Endoscopic Transoral-Transpharyngeal Approach
Authors: Zhong Sheng , Ren Jiaxin , Zhang Yuan , Li Weihang , Li Hui , Song Siying , Zhao Gang , Cheng Ye
Published: May 2018

Purpose:

This study aims to provide accurate and comprehensive data of craniocervical junction and its peripheral structures in order to provide a profound insight of craniocervical junction as well as to avoid complications during surgical procedures related to it.

Methods:

Computed tomographic angiography (CTA) images of 120 individuals were reviewed, the measurements were performed on coronal, sagittal, and axial planes after 3-dimensional volume reconstruction. The authors measured pharyngeal tubercle, foramen magnum, and tuberculum anterius atlantis, which located based on the position of incisor. The anatomic features of other important bony landmarks, internal carotid artery, and vertebral artery were also fully studied so as to avoid being injured during the transoral-transpharyngeal procedure.

Results:

During the endoscopic surgery to craniocervical junction, the bending angle of neuroendoscopy should be 14.27 ± 4.51° and the entering depth should be about 72.57 ± 8.72 mm. It is safe to work within the angle of 77.73 ± 3.15° in axial plane and the safe penetration width from the axial midline is 20.05 ± 3.11 mm in the level of foramina magnum. The distance from axial middle line to hypoglossal canal, external opening of carotid canal, and inner edge of jugular foramen was 9.78 ± 0.72, 24.50 ± 1.26, and 24.33 ± 1.68 mm, respectively.

Conclusions:

These data in this study are valuable for neurosurgeons in clinical practice to reduce the possibility of complications and maximize the safety of surgeries; these data also contribute to the understanding of the anatomy of craniocervical junction and its surrounding structures.
The Effect of Mandibular Distraction Osteogenesis on Weight Velocity in Infants With Severe Pierre Robin Syndrome
Authors: Luo Dongyuan , Chen Yiyang , Wang Hongtao , Li Ting , Fan Li , Wenli Wu , Jiayu Liu , Jiansuo Hao
Published: May 2018

Mandibular distraction osteogenesis (MDO) effectively improves airway obstruction in Pierre Robin syndrome (PRS) patients. However, whether or not early MDO is beneficial to the development of children is still controversial. To observe the influence of PRS patient age at the time of MDO on their development, the authors retrospectively analyzed preoperative and postoperative body weight in 41 children with PRS who underwent MDO treatment from 2014 to 2016. The body weight of the infants at the time of birth, first visit, MDO surgery, distractor removal, and palatoplasty surgery was recorded. The body weight percentile significantly fell from 34.4 ± 5.8 at birth to 13.1 ± 3.6 at the time of MDO (P < 0.001), and increased to 28.3 ± 5.3 at distractor removal (P < 0.05) following MDO, finally reaching 42.4 ± 6.5 at palatoplasty surgery (P < 0.001). The infants who accepted MDO treatment at <1 month of age maintained a significantly higher body weight percentile than those who accepted MDO surgery at 1 to 3 months or 4 to 7 months of age, at the time of both MDO and palatoplasty surgeries (P < 0.05). After the MDO procedure, the body weight percentiles of the PRS infants with a cleft palate were comparable to those without a cleft palate at the time of palatoplasty surgery. The body weight percentile quickly climbed to 74.0 ± 35.2 at the time of distractor removal, from 46.7 ± 18.2 at the time of MDO. In conclusion, early MDO was beneficial in severe cases of PRS for patients to recover body weight and to allow for earlier palatoplasty surgery.
Hydrogen-Rich Saline Attenuates Acute Lung Injury Induced by Limb Ischemia/Reperfusion via Down-Regulating Chemerin and NLRP3 in Rats
Authors: Zou Run , Wang Mao-Hua , Chen Ye , Fan Xin , Yang Bo , Du Juan , Wang Xiao-Bin , Liu Ke-Xuan , Zhou Jun
Published: May 2018

Limb ischemia/reperfusion (LI/R) injury is associated with high morbidity and mortality. The hypothesis of this study is that hydrogen-rich solution could attenuate

acute lung injury and improve mortality via chemerin and NLRP3 after LI/R in rats. A rat model of LI/R was performed by clamping the bilateral femoral arteries for 3 h followed by reperfusion. Hydrogen-rich saline (HRS) was administered intraperitoneally (10 mL/kg or 2.5 mL/kg) when the atraumatic micro clips were released. The rats were euthanized at 2 h after reperfusion and then the arterial blood and lung specimens were harvested for further analyses. Meanwhile, survival rate was observed. The results showed that HRS improved the survival rate and attenuated pulmonary edema, injury, and apoptosis. HRS also decreased the levels of tumor necrosis factor-α, interleukin-6, myeloperoxidase and malondialdehyde, and increased the activity of superoxide dismutase in serum and lung after the LI/R event. HRS downregulated the expression of chemerin and NLRP3 in lung. The study demonstrated that chemerin and NLRP3 could serve as important response factors that were involved in the lung injury following LI/R. HRS could significantly attenuate LI/R-mediated acute lung injury, at least in part, by inhibiting the activated chemerin/NLRP3 signaling pathway.
The novel oral anticoagulants (NOACs) have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI
Authors: Zeeshan Muhammad , Jehan Faisal , O’Keeffe Terence , Khan Muhammad , Zakaria El Rasheid , Hamidi Mohammad , Gries Lynn , Kulvatunyou Narong , Joseph Bellal
Published: May 2018

INTRODUCTION

Novel oral anticoagulant (NOAC) use is increasing in trauma patients. The reversal of these agents after hemorrhage is still evolving. The aim of our study was to evaluate outcomes after traumatic brain injury in patients on NOACs.

METHODS

3-year (2014–2016) analysis of our prospectively maintained traumatic brain injury (TBI) database. We included all TBI patients with intracranial hemorrhage (ICH) on anticoagulants. Patients were stratified into two groups, those on NOACs and on warfarin, and were matched in a 1:2 ratio using propensity score matching for demographics, injury and vital parameters, type, and size of ICH. Outcome measures were progression of ICH, mortality, skilled nursing facility (SNF) disposition, and hospital and intensive care unit (ICU) length of stay (LOS).

RESULTS

We analyzed 1,459 TBI patients, of which 210 patients were matched (NAOCs, 70; warfarin, 140). Matched groups were similar in age (p = 0.21), mechanism of injury (p = 0.61), Glasgow Coma Scale (GCS) score (p = 0.54), Injury Severity Score (p = 0.62), and type and size of ICH (p = 0.09). Patients on preinjury NOACs had higher rate of progression (p = 0.03), neurosurgical intervention (p = 0.04), mortality (p = 0.04), and longer ICU LOS (p = 0.04) compared with patients on warfarin. However, there was no difference in hospital LOS (p = 0.22) and SNF disposition (p = 0.14). On sub-analysis of severe TBI patients (GCS ≤ 8), rate of progression (p = 0.59), neurosurgical intervention (p = 0.62), or mortality (p = 0.81) was similar in both groups.

CONCLUSIONS

The use of NOACs generally carries a high risk of bleeding and can be detrimental in head injuries with ICH. NOAC use is associated with increased risk of progression of ICH, neurosurgical intervention, and mortality after a mild and moderate TBI. Primary care physicians and cardiologists need to reconsider the data on the need for anticoagulation and the type of agent used and weigh it against the risk of bleeding. In addition, development of reversal agents for the NOACs and implementation of a strict protocol for the reversal of these agents may lead to improved outcomes.

LEVEL OF EVIDENCE

Therapeutic studies, level III.
Domino Liver Transplant in Maple Syrup Urine Disease: Technical Details of Cases in Which the First Surgery Involved a Living Donor
Authors: Roda Karina M. O. , Vincenzi Rodrigo , Fonseca Eduardo A. , Benavides Marcel , Turine Plínio , Afonso Rogerio C. , Tonon Tassia , Schwartz Ida , Miura Irene K. , Pugliese Renata , Porta Gilda , Chapchap Paulo , Seda Neto Joao
Published: May 2018

Background.

Data describing the technical aspects of living donor (LD) domino liver transplantation (DLT) in maple syrup urine disease (MSUD) are limited. The largest published series includes only 3 cases. One great challenge of this procedure is to ensure adequate vascular stumps for the LD, the MSUD patient, and the recipient of the domino graft. Here, we describe our experience in 11 cases of LD-DLT in MSUD, highlighting the technical aspects of LD-DLT.

Methods.

From September 2012 to September 2017, 11 patients with MSUD underwent LD liver transplantation at our institution, and MSUD livers were used as domino grafts in 11 children.

Results.

(1) MSUD patients: 10 patients received a left lateral segment. The donor’s left hepatic vein (HV) was anastomosed to the confluence of the recipient’s 3 HVs. No vascular grafts (VG) were required for portal vein (PV) anastomosis. Single arterial anastomosis was performed with microsurgery in 10 of 11 patients. (2) MSUD graft recipients: In 8 cases, HV reconstruction was performed between the graft’s HV confluence and the recipient’s HV confluence, and in 3 cases, a vena cava triangulation was necessary; 6 MSUD grafts required HV venoplasty. No VG were needed for HV reconstruction. VG were used for PV reconstruction in 3 cases due to sclerotic PV. In 2 cases, double arterial anastomoses were performed in the MSUD liver. All patients remain alive and well.

Conclusions.

Living donor liver transplantation followed by DLT for MSUD is a complex procedure and demands technical refinement. Special attention must be paid to vascular reconstruction.
Donating Another Person’s Kidney: Avoiding the Discard of Organs by Retransplantation
Authors: Veale Jeffrey L. , Lum Erik L. , Cowan Nicholas G. , Wong Melissa , Skovira Kelly A. , Armijo Mauri J. , Danovitch Gabriel M. , Mone Thomas D.
Published: May 2018

Background

Procurement and retransplantation of a previously transplanted kidney reclaim a functioning organ that would otherwise have been discarded.

Methods

Case series of 3 retransplantation cases within the course of 1 calendar year.

Results

These cases illustrate how to overcome the immunological, logistical, and technical barriers that have thus far limited the potential of this approach. Within this series, we report kidney reuse weeks and years after the original transplantation, as well as the previously undescribed “living donation of a deceased donor kidney”.

Conclusions

Retransplantation of previously transplanted kidneys can be performed successfully and should be considered in the face of the current organ shortage.
Week-long imaging of cell divisions in the Arabidopsis root meristem
Authors: Rahni Ramin , Birnbaum Kenneth D.
Published: May 2018

Characterizing the behaviors of dynamic systems requires capturing them with high temporal and spatial resolution. Owing to its transparency and genetic tractability, theArabidopsis thalianaroot lends itself well to live imaging when combined with cell and tissue-specific fluorescent reporters. We developed a novel 4D imaging method that utilizes simple confocal microscopy and readily available components to track cell divisions in the root stem cell niche and surrounding region for up to one week. This new setup allows us to finely analyze meristematic cell division rates that lead to patterning. Using this method, we performed a direct measurement of cell division intervals within and around the root stem cell niche. The results reveal a short, steep gradient of cell division in proximal stem cells, with progressively more rapid cell division rates from QC, to cells in direct contact with the QC (initials), to their immediate daughters, after which division rates appear to become more homogeneous. These results provide a baseline to study how perturbations in signaling could affect cell division patterns in the root meristem.
Human and Rodent Temporal Lobe Epilepsy is Characterized by Changes in O-GLCNAC Homeostasis that can be Reversed to Dampen Epileptiform Activity
Authors: Sanchez Richard G. , Parrish R. Ryley , Rich Megan , Webb William M. , Lockhart Roxanne M. , Nakao Kazuhito , Ianov Lara , Buckingham Susan C. , Cunningham Mark , Broadwater Devin R. , Jenkins Alistar , De Lanerolle Nihal C , Eid Tore , Riley Kristen , Lubin Farah D.
Published: May 2018

Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that integrate energy supply with demand. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to determine whether changes in OGT/OGA cycling and disruptions in protein O-GlcNAcylation occur in the epileptic hippocampus. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
Limited One-time Sampling Irregularity Map (LOTS-IM): Automatic Unsupervised Quantitative Assessment of White Matter Hyperintensities in Structural Brain Magnetic Resonance Images
Authors: Rachmadi Muhammad Febrian , Valdés-Hernández Maria del C. , Li Hongwei , Guerrero Ricardo , Meijboom Rozanna , Wiseman Stewart , Waldman Adam , Zhang Jianguo , Rueckert Daniel , Komura Taku
Published: May 2018

We present a complete study of limited one-time sampling irregularity map (LOTS-IM), a fully automatic unsupervised approach to extract brain tissue irregularities in magnetic resonance images (MRI), including its application and evaluation for quantitative assessment of white matter hyperintensities (WMH) of presumed vascular origin and assessing multiple sclerosis (MS) lesion progression. LOTS-IM is unique compared to similar other methods because it yields irregularity map (IM) which represents WMH as irregularity values, not probability values, and retains the original MRI’s texture information. We tested and compared the usage of IM for WMH segmentation on T2-FLAIR MRI with various methods, including the well established unsupervised WMH segmentation Lesion Growth Algorithm from the public toolbox Lesion Segmentation Toolbox (LST-LGA), conventional supervised machine learning schemes andstate-of-the-artsupervised deep neural networks. In our experiments, LOTS-IM outperformed unsupervised method LST-LGA, both in performance and processing speed, thanks to the limited one-time sampling scheme and its implementation on GPU. Our method also outperformed supervised conventional machine learning algorithms (i.e., support vector machine (SVM) and random forest (RF)) and deep neural networks algorithms (i.e., deep Boltzmann machine (DBM) and convolutional encoder network (CEN)), while yielding comparable results to the convolutional neural network schemes that rank top of the algorithms developed up to date for this purpose (i.e., UResNet and UNet). The high sensitivity of IM on depicting signal change deems suitable for assessing MS progression, although care must be taken with signal changes not reflective of a true pathology.
Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia
Authors: Merker Matthias , Barbier Maxime , Cox Helen , Rasigade Jean-Philippe , Feuerriegel Silke , Kohl Thomas A. , Diel Roland , Borrell Sonia , Gagneux Sebastien , Nikolayevskyy Vladyslav , Andres Sönke , Nübel Ulrich , Supply Philip , Wirth Thierry , Niemann Stefan
Published: May 2018

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.

We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).

One MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.

The genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.
Applications for deep learning in ecology
Authors: Christin Sylvain , Hervet Éric , Lecomte Nicolas
Published: May 2018

A lot of hype has recently been generated around deep learning, a group of artificial intelligence approaches able to break accuracy records in pattern recognition. Over the course of just a few years, deep learning revolutionized several research fields such as bioinformatics or medicine. Yet such a surge of tools and knowledge is still in its infancy in ecology despite the ever-growing size and the complexity of ecological datasets. Here we performed a literature review of deep learning implementations in ecology to identify its benefits in most ecological disciplines, even in applied ecology, up to decision makers and conservationists alike. We also provide guidelines on useful resources and recommendations for ecologists to start adding deep learning to their toolkit. At a time when automatic monitoring of populations and ecosystems generates a vast amount of data that cannot be processed by humans anymore, deep learning could become a necessity in ecology.
Overcoming bottlenecks for in vitro synthesis and initial structural insight of ice nucleating protein InaZ
Authors: Novikova Irina V. , China Swarup , Evans James E.
Published: May 2018

Unlike inorganic or other synthetic alternatives, ice nucleating proteins (INPs) remain the most efficient ice nuclei today. Their potential applications in cryo-preservation, biomedicine, food industry and in the modulation of climate are widespread. Nevertheless, over several decades, cell-based recombinant methods have experienced multiple difficulties expressing these large proteins in full-length and in necessary yields while retaining functionality. As a result, our understanding of the structure and ice nucleation mechanism for this class of proteins is incomplete, and, most importantly, the full extent of possible applications unrealized. Using a wheat-germ cell-free expression pipeline, we successfully expressed and purified full-length ice nucleating protein InaZ fromPseudomonas syringae, known as a model INP. High protein yield and solubility has been achieved using this system. Ice nucleation experiments inside a dynamic environmental scanning electron microscope (ESEM) confirmed that the produced InaZ products remain functional. Preliminary structural assessments of these proteins using Transmission Electron Microscopy (TEM) showed experimental evidence for their structural organization as fibrils. We believe that the current platform will be suitable for expressing other INPs of interest and can be further employed as new engineering system either for industrial or scientific needs.
Genome sequence ofJaltomataaddresses rapid reproductive trait evolution and enhances comparative genomics in the hyper-diverse Solanaceae
Authors: Wu Meng , Kostyun Jamie L. , Moyle Leonie C.
Published: May 2018

Within the economically important plant family Solanaceae,Jaltomatais a rapidly evolving genus that has extensive diversity in flower size and shape, as well as fruit and nectar color, among its ∼80 species. Here we report the whole-genome sequencing, assembly, and annotation, of one representative species (Jaltomata sinuosa) from this genus. Combining PacBio long-reads (25X) and Illumina short-reads (148X) achieved an assembly of approximately 1.45 Gb, spanning ∼96% of the estimated genome. 96% of curated single-copy orthologs in plants were detected in the assembly, supporting a high level of completeness of the genome. Similar to other Solanaceous species, repetitive elements made up a large fraction (∼80%) of the genome, with the most recently active element,Gypsy, expanding across the genome in the last 1-2 million years.

Computational gene prediction, in conjunction with a merged transcriptome dataset from 11 tissues, identified 34725 protein-coding genes. Comparative phylogenetic analyses with six other sequenced Solanaceae species determined thatJaltomatais most likely sister toSolanum, although a large fraction of gene trees supported a conflicting bipartition consistent with substantial introgression betweenJaltomataandCapsicumafter these species split. We also identified gene family dynamics specific toJaltomata, including expansion of gene families potentially involved in novel reproductive trait development, and loss of gene families that accompanied the loss of self-incompatibility. This high-quality genome will facilitate studies of phenotypic diversification in this rapidly radiating group, and provide a new point of comparison for broader analyses of genomic evolution across the Solanaceae.
The evolutionary game of interspecific mutualism in the multi-species model
Authors: Shibasaki Shota
Published: May 2018

Mutualistic interspecific interactions, including Müllerian mimicry and division of labor, are common in nature. In contrast to antagonistic interactions, where faster evolution is favored, mutualism can favor slower evolution under some conditions. This is called the Red King effect. After Bergstrom and Lachmann (2003) proposed Red King effect, it has been investigated in two species models. However, biological examples suggest that the mutualisms can include three or more species. Here, I modeled the evolutionary dynamics of mutualism in communities where there exist two or more species, and all species mutually interact with one another. Regardless of the number of species in the community, it is possible to derive conditions for the stable equilibria. Although there exist nonlinear relationship between the evolutionary rates and the evolutionary fate of each species in the multi-species communities, the model suggests that it is possible to predict whether the faster evolution is favored or disfavored for the relatively fast species; on the other hand, it is difficult to predict the evolutionary fate of relatively slow species because the evolutionary dynamics of the slow species is affected by the evolutionary fate of the fast species.
Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images
Authors: Caicedo Juan C. , Roth Jonathan , Goodman Allen , Becker Tim , Karhohs Kyle W , Broisin Matthieu , Csaba Molnar , McQuin Claire , Singh Shantanu , Theis Fabian , Carpenter Anne E.
Published: May 2018

Identifying nuclei is often a critical first step in analyzing microscopy images of cells, and classical image processing algorithms are most commonly used for this task. Recent developments in deep learning can yield superior accuracy, but typical evaluation metrics for nucleus segmentation do not satisfactorily capture error modes that are relevant in cellular images. We present an evaluation framework to measure accuracy, types of errors, and computational efficiency; and use it to compare deep learning strategies and classical approaches. We publicly release a set of 23,165 manually annotated nuclei and source code to reproduce experiments and run the proposed evaluation methodology. Our evaluation framework shows that deep learning improves accuracy and can reduce the number of biologically relevant errors by half.