bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Steroids With Antibiotics on Admission for Children With Orbital Cellulitis
Authors: Chen Lena , Silverman Nora , Wu Andrew , Shinder Roman
Published: April 2017

Purpose:

To compare the outcomes of children with orbital cellulitis treated with intravenous (IV) dexamethasone and antibiotics on admission to patients treated with antibiotics alone.

Methods:

Prospective comparative interventional study. Forty-three children admitted to a tertiary institution with orbital cellulitis were enrolled. On admission, all patients were started on broad spectrum IV antibiotics and parents were offered IV dexamethasone (0.3 mg/kg/d every 6 hours for 3 days). Patients whose parents refused steroid treatment served as the control group.

Results:

Twenty-eight (65%) patients received IV steroids and antibiotics on admission while 15 (35%) received IV antibiotics alone. Children who received IV steroids had significantly shorter hospital stays than those who did not receive steroids (3.8 ± 0.2 days vs. 6.7 ± 0.3 days; p < 0.001). This was true both for children who underwent surgery (5/28 with steroids, 3/15 without; 5.0 ± 0.7 days vs. 7.3 ± 1.2 days; p = 0.011) and for those who did not require surgical intervention (23/28 with steroids, 12/15 without; 3.6 ± 0.6 and 6.5 ± 1.0 days; p < 0.001). Side effects of steroid treatment were mild and did not require termination of therapy. During follow up, all study patients had returned to their baseline health without any cases of decreased vision or disease recurrence.

Conclusions:

The results of the current study give additional evidence to the relative safety and efficacy of systemic steroid use concurrently with IV antibiotics in children with orbital cellulitis. This is the first study to recommend IV steroids on hospital admission and a standardized dosing regimen. Children who received steroids had a shorter hospital stay than those who did not.
Volumization of the Brow at the Time of Blepharoplasty: Treating the Eyebrow Fat Pad as an Independent Unit
Authors: Vrcek Ivan , Chou Eva , Somogyi Marie , Shore John W.
Published: April 2017

Purpose:

Loss of volume in the sub-brow fat pad with associated descent of the eyebrow is a common anatomical finding resulting in both functional and aesthetic consequences. A variety of techniques have been described to address brow position at the time of blepharoplasty. To our knowledge, none of these techniques treat the sub-brow fat pad as an isolated unit. Doing so enables the surgeon to stabilize and volumize the brow without resultant tension on the blepharoplasty wound. The authors describe a technique for addressing volume loss in the eyebrow with associated brow descent that treats the sub-brow fat pad as an isolated unit.

Methods:

A retrospective review of all patients undergoing brow ptosis repair by a single surgeon (J.W.S.) over an 11-month period was performed.

Results:

Eighteen patients and 33 brows underwent the technique described. Patients were followed for an average of 11 weeks (range: 4 weeks to 20 weeks). All patients preoperatively displayed both visually significant dermatochalasis and brow descent below the orbital rim. Evaluation of pre- and postoperative photos demonstrates successful volumization of the brow with skin redraping without focal dimpling or undue tension on the eyelid wound.

Conclusions:

Performing a dissection that allows the sub-brow fat pad to be elevated in isolation from the overlying orbicularis and underlying periosteum allows for volumization and of the brow without compromising closure. This technique is a safe and effective means of volumizing the brow and treating secondary brow descent.
C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study
Authors: Schistad Elina Iordanova , Stubhaug Audun , Furberg Anne-Sofie , Engdahl Bo Lars , Nielsen Christopher Sivert
Published: April 2017

The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.
Clinical usefulness of controlled attenuation parameter to screen hepatic steatosis for potential donor of living donor liver transplant
Authors: Hong Young Mi , Yoon Ki Tae , Cho Mong , Chu Chong Woo , Rhu Je Ho , Yang Kwang Ho , Lee Jun Woo
Published: April 2017

Objective

Hepatic steatosis is associated with an increased risk of graft loss. Although the controlled attenuation parameter (CAP), a process based on transient elastography, has been suggested as a noninvasive method of assessing hepatic steatosis, to date, there is no study on the usefulness of CAP as a single screening tool for detecting hepatic steatosis in potential living donor liver. We evaluated the accuracy of CAP for detecting hepatic steatosis in potential liver donors.

Patients and methods

All potential donors of living-donor liver transplantation who underwent a CAP assessment and ultrasonography-guided liver biopsy were enrolled. The steatosis grades were as follows: S0 less than 5%; S1, 5–33%; S2, 34–66%; and S3, more than 66%.

Results

According to the liver biopsies, 19 (34.5%) patients had S0, 30 (54.5%) patients had S1, and 6 (11.0%) patients had S2. The CAP value was correlated positively with BMI (r=0.242, P=0.01), waist circumference (r=0.268, P=0.006), hip circumference (r=0.334, P=0.001), Magnetic resonance fat signal fraction (r=0.465, P=0.001), and histologic steatosis grade (r=0.542, P=0.001). The area under the receiver operator characteristic curve for the diagnosis of steatosis (≥S2) by CAP was 0.88 (sensitivity 83.3% and specificity 81.6% at a cutoff value of 276 dB/m, P<0.0001).

Conclusion

This study suggests that CAP, as a simple and noninvasive preoperative assessment for hepatic steatosis, may be sufficient for identifying and thus excluding significant hepatic steatosis (>33%) in potential liver donors.
Distinct functions of histone H3, lysine 4 methyltransferases in normal and malignant hematopoiesis
Authors: Yang Weiwei , Ernst Patricia
Published: April 2017

Purpose of review

Histone H3, lysine 4 (H3K4) methylation is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express six main histone methyltransferase (HMT) enzymes that modify H3K4 by monomethylation, dimethylation or trimethylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem data, revealing how these enzymes function.

Recent findings

Murine models have been employed to conditionally or constitutively knockout HMTs (MLL1/KMT2A, MLL2/KMT2B, MLL3/KMT2C, MLL4/KMT2D, SETD1A/KMT2F and SETD1B/KMT2G) as well as specific domains or partners of these enzymes in normal hematopoietic populations and in the context of hematologic malignancies. These studies demonstrate that global or gene-specific changes in H3K4 modification levels can be attributed to particular enzymes in particular tissues.

Loss-of-function studies indicate largely nonoverlapping roles of the six H3K4 HMTs. These roles are not all necessarily due to differences in enzymatic activity and are not always accompanied by large global changes in histone modification. Both gain-of-function and loss-of-function mutations in hematologic malignancy are restricted to MLL1 and MLL3/MLL4, but emerging data indicate that SETD1A/SETD1B and MLL2 can be critical in leukemia as well.
The new frontier of epigenetic heterogeneity in B-cell neoplasms
Authors: Dominguez Pilar M. , Teater Matt , Shaknovich Rita
Published: April 2017

Purpose of review

There is mounting evidence that heterogeneity of the epigenome is a feature of many cancers, including B-cell lymphomas, and presents important clinical implications. The purpose of this review is to explain the biological and clinical relevance of this epigenetic phenomenon in B-cell neoplasms.

Recent findings

Here, we summarize new findings demonstrating that B-cell lymphomas display increased DNA methylation heterogeneity compared to their normal counterparts. This plasticity of cytosine methylation manifests both as intertumor and intratumor heterogeneity and is associated with worse prognosis and poor clinical outcome in lymphoma patients. Recent studies of different subtypes of B-cell lymphomas have revealed that epigenetic aberrations and heterogeneous cytosine methylation patterning are common features of all neoplasms derived from B-lymphocytes, irrespective of maturation stage. With regard to mechanisms driving this process, recent reports suggest that cytosine methylation heterogeneity arises through passive and active processes. One factor implicated in active generation of cytosine methylation heterogeneity is activation-induced cytidine deaminase, which mediates DNA methylation changes and introduces epigenetic heterogeneity in normal germinal center B cells, the cells of origin of mature B-cell neoplasms such as diffuse large B-cell lymphoma and follicular lymphoma.

Understanding the scope and mechanism of epigenetic heterogeneity in cancer is of paramount importance to our understanding of clonal plasticity and treatment responses in B-cell lymphomas.
Rehabilitation of Guillain-Barré syndrome patients: an observational study
Authors: Novak Primož , Šmid Sonja , Vidmar Gaj
Published: April 2017

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy resulting in severe impairments of many body structures and functions with consequent limitations of activities and participation. The aim of our study was to evaluate rehabilitation outcome in these patients. Forty-five (20 women, 25 men) with GBS patients who had completed primary comprehensive rehabilitation were included in the study. Medical Research Council Scale for Muscle Strength was used for assessment of lower-limb function. Patients’ activities were assessed using the Functional Independence Measure and two walking tests (6 min and 10 m). The patients were also described using an adapted International Classification of Functioning, Disability and Health checklist. Assessment was performed at admission and at discharge. Clinically important and statistically significant improvements were found in all outcome measures. Strong and significant correlations were found between the outcome measures. International Classification of Functioning, Disability and Health coding also clearly reflected the progress. Improvement in patients’ activities increased statistically significantly with time for up to 3 months of rehabilitation. The outcome was not related to the time interval from establishing the diagnosis to the start of rehabilitation. Hence, multidisciplinary care for GBS patients is effective, because clinically important and statistically significant improvements regarding body functions and activities are achieved during relatively short inpatient rehabilitation.
Psychometric properties of the Oswestry Disability Index
Authors: Saltychev Mikhail , Mattie Ryan , McCormick Zachary , Bärlund Esa , Laimi Katri
Published: April 2017

The aim of this study was to investigate the psychometric properties of the Oswestry Disability Index (ODI) in a large cross-sectional cohort of individuals with chronic low back pain by defining its internal consistency, construct structure and validity, and its ability to differentiate between different degrees of functional limitation. A total of 837 consecutive outpatient patients with low back pain were studied. The internal consistency of ODI was assessed by Cronbach's α, construct structure by exploratory factor analysis, construct validity by confirmatory factor analysis, and discrimination was determined by item response theory analysis. The ODI showed good internal consistency (α=0.85). Explanatory factor analysis showed that ODI is a unidimensional test measuring functional level and nothing else. The confirmatory factor analysis showed that the standardized regression weights of all ODI items were relatively high, varying from 0.5 to 0.7. The item response theory analysis suggested that eight out of 10 ODI items have a close to perfect ability to measure functional limitations in accordance with the actual severity of disability experienced by the respondents. Discrimination of all the items was high to perfect (1.08–2.01). The test characteristic and test information curves showed that the discriminative ability of the ODI is superior at higher levels of disability. The present data showed that the ODI is an internally consistent, unidimensional scale with overall excellent construct validity and ability to discriminate the severity of functional disability. The analysis suggests that the ODI may better distinguish between the relative degrees of function at above-average disability levels.
Reporting and Staging of Testicular Germ Cell Tumors
Authors: Verrill Clare , Yilmaz Asli , Srigley John R. , Amin Mahul B. , Compérat Eva , Egevad Lars , Ulbright Thomas M. , Tickoo Satish K. , Berney Daniel M. , Epstein Jonathan I.
Published: April 2017

The International Society of Urological Pathology held a conference devoted to issues in testicular and penile pathology in Boston in March 2015, which included a presentation and discussion led by the testis microscopic features working group. This conference focused on controversies related to staging and reporting of testicular tumors and was preceded by an online survey of the International Society of Urological Pathology members. The survey results were used to initiate discussions, but decisions were made by expert consensus rather than voting. A number of recommendations emerged from the conference, including that lymphovascular invasion (LVI) should always be reported and no distinction need be made between lymphatic or blood invasion. If LVI is equivocal, then it should be regarded as negative to avoid triggering unnecessary therapy. LVI in the spermatic cord is considered as category pT2, not pT3, unless future studies provide contrary evidence. At the time of gross dissection, a block should be taken just superior to the epididymis to define the base of the spermatic cord, and direct invasion of tumor in this block indicates a category of pT3. Pagetoid involvement of the rete testis epithelium must be distinguished from rete testis stromal invasion, with only the latter being prognostically useful. Percentages of different tumor elements in mixed germ cell tumors should be reported. Although consensus was reached on many issues, there are still areas of practice that need further evidence on which to base firm recommendations.
A Novel Numerical Scoring System for Melanoma Tumor-infiltrating Lymphocytes Has Better Prognostic Value Than Standard Scoring
Authors: Saldanha Gerald , Flatman Katarina , Teo Kah Wee , Bamford Mark
Published: April 2017

The purpose of this study was to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) in melanoma and to determine whether a simpler numerical scoring system would be more effective. In total, 655 patients presenting to a UK teaching hospital with primary invasive melanoma were analyzed. TILs were rescored using the standard Clark’s method and univariable and multivariable analyses of the effect of TILs on overall survival (OS), disease-specific survival (DSS), and metastasis-free survival (MFS) was assessed using Cox regression. In total, 30 (5%) melanomas showed absent, 464 (71%) nonbrisk, and 161 (24%) brisk TILs. There was a statistically significant relationship between TILs and Breslow thickness, age, melanoma type, mitotic rate, and histologic regression. TIL grade was a significant predictor of MFS in multivariable analysis (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.77) but was not significant for OS or DSS. By contrast, when a simple numerical TIL percentage score was used this was a strong predictor of OS (HR, 0.55; 95% CI, 0.38-0.78), DSS (HR, 0.25; 95% CI, 0.14-0.44), and MFS (HR, 0.32; 95% CI, 0.21-0.51) in multivariable analysis. The percentage TIL score was also significant when adjusted for the prognostic gold standard, American Joint Committee on Cancer stage: OS (HR, 0.66; 95% CI, 0.46-0.95), DSS (HR, 0.33; 95% CI, 0.19-0.60), and MFS (HR, 0.41; 95% CI, 0.26-0.65). The TIL percentage score was subsequently validated in new cases. In summary, this study strongly confirms that higher amounts of TILs are associated with better prognosis and in addition demonstrates the value of a simplified numerical TIL scoring system.
Panfacial Fat Injection Approach in Young Asian Patients for Facial Contouring: A Goal-Oriented Classification Method Based on the Facial Fat Compartments Theory
Authors: Li Zhanqiang , Li Jie , Ma Jiguang , Li Xin , Wang Keming , Wang Chunhu , Qi Zuoliang
Published: April 2017

Background:

In Asia, young patients tend to undergo panfacial fat injection for facial contouring rather than for rejuvenation. Although the procedure is widely performed, there is no single approach that has been shown to have consistent results.

Method:

One personalized approach based on the facial fat compartment theory is presented here. Under the theory of facial fat compartments, the injection area is classified into functional zones and transition zones. A retrospective review of 105 cases over 6 years was performed to evaluate the effectiveness of this approach.

Results:

Follow-up ranged from 6 to 47 months. Satisfactory results were achieved in 96 percent of cases. Typical cases were also reviewed.

Conclusions:

In the authors’ view, this approach is safe and easy to learn, and produces aesthetically satisfactory results. The approach is stable, and satisfactory clinical results were achieved under the guidance of the facial fat compartment theory, which in turn verified the accuracy of this theory.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Current Status of Parkinsonism-Related Adverse Events and Associated Drugs in Korea
Authors: Kim Siin , Suh Hae Sun
Published: April 2017

Objective

The aim of the study was to explore the current status of drug-induced parkinsonism and drugs possibly related to drug-induced parkinsonism in Korea.

Methods

We conducted a cross-sectional study using the Korea Adverse Event Reporting System database between July 1, 2010, and June 30, 2015. We identified all adverse event reports associated with parkinsonism.

Results

There were 1402 adverse event reports associated with parkinsonism. The number of adverse event reports has increased annually. Among the 1499 drugs associated with parkinsonism, the most common were metoclopramide (49.77%) and paliperidone (16.14%). The major therapeutic groups (the third level of the Anatomical Therapeutic Chemical code) were propulsives (53.87%) and antipsychotics (35.58%). The mean time of onset of parkinsonism was 34.9 days. However, the time of onset of parkinsonism varied by drug, for example, it was 4.6 days for metoclopramide and 37.2 days for paliperidone.

Conclusions

Metoclopramide and antipsychotics were reported in most adverse event reports associated with parkinsonism in Korea.
Intravenous Administration Errors Intercepted by Smart Infusion Technology in an Adult Intensive Care Unit
Authors: Ibarra-Pérez Rebecca , Puértolas-Balint Fabiola , Lozano-Cruz Elizabeth , Zamora-Gómez Sergio E. , Castro-Pastrana Lucila I.
Published: April 2017

Objectives

The aim of the study was to investigate the efficacy of intravenous (IV) smart pumps with drug libraries and dose error reduction system (DERS) to intercept programming errors entailing high risk for patients in an adult intensive care unit (ICU).

Methods

A 2-year retrospective study was conducted in the adult ICU of the Hospital Juárez de México in Mexico City to evaluate the impact of IV smart pump/DERS (Hospira MedNet) technology implementation. We conducted a descriptive analysis of the reports generated by the system’s software from April 2014 through May 2016. Our study focused on the upper hard limit alerts and used the systems’ variance reports and IV Medication Harm Index methodology to determine the severity of the averted overdoses for medications with the highest number of edits.

Results

The system monitored 124,229 infusion programs and averted on 36,942 deviations of the preset safe limits. Upper hard limit alerts accounted for 26.4% of pump reprogramming events. One hundred sixty-six significant administration errors were intercepted and prevented, and IV Medication Harm Index analysis identified 83 of them as highest-risk averted overdoses with insulin accounting for 51.8% of those. The rate of compliance with the safety software during the study period was 69.8%.

Conclusions

Our study contributes additional evidence of the impact of IV smart pump/DERS technology. These pumps effectively intercepted severe infusion errors and significantly prevented adverse drug events related to dosing. Our results support the implementation of this technology in ICUs as a minimum safety standard and could help drive an IV infusion safety initiative in Mexico.
Bowel Angioedema Associated With Iodinated Contrast Media
Authors: Seo Nieun , Chung Yong Eun , Lim Joon Seok , Song Mi Kyung , Kim Myeong-Jin , Kim Ki Whang
Published: April 2017

Objective

Bowel angioedema is an acute adverse reaction to iodinated contrast media (CM) that involves the gastrointestinal tract. We aimed to investigate the incidence and predisposing factors of iodinated CM-associated bowel angioedema during computed tomography (CT) examinations.

Materials and Methods

This study was approved by our institutional review board, and informed consent was waived due to its retrospective design. From July 2013 to July 2015, adult patients with a history of adverse reactions to iodinated CM during CT (group A, n = 427) and patients without adverse reactions matched for age and sex with the propensity-score matching method (group B, n = 427) were studied. Contrast media–associated bowel angioedema was determined when bowel wall thickness increased after contrast enhancement compared with the precontrast scan. Potential predisposing factors including patient demographics, symptoms and time of adverse reactions, and CM-related factors were compared between patients with and without angioedema in group A. In addition, the incidence of bowel angioedema was compared between groups A and B.

Results

The incidence of CM-associated bowel angioedema in group A was 3.3% (14/427) in the per-patient analysis and 2.6% (15/578) in the per-examination analysis. The CM–associated bowel angioedema involved the distal duodenum and/or proximal jejunum and showed long-segmental circumferential bowel wall thickening on CT. None of the studied predisposing factors was different between patients with and without bowel angioedema (P > 0.05). The incidence of CM-associated bowel angioedema in group B was 1.9% (8/427) and 1.7% (8/458) for per-patient and per-examination analyses, respectively, and these rates were not significantly different between groups A and B (P = 0.346 and P = 0.370, respectively).

Conclusions

The incidence of CM-associated bowel angioedema during CT was 1.7% to 3.3%, and none of the studied predisposing factors was associated with bowel angioedema.
Improved Retention of Chest Compression Psychomotor Skills With Brief “Rolling Refresher” Training
Authors: Niles Dana E. , Nishisaki Akira , Sutton Robert M. , Elci Okan U. , Meaney Peter A. , O'Connor Kathleen A. , Leffelman Jessica , Kramer-Johansen Jo , Berg Robert A. , Nadkarni Vinay
Published: April 2017

Introduction

High-quality cardiopulmonary resuscitation (CPR) is critical to improve survival from cardiac arrest. However, cardiopulmonary resuscitation knowledge and psychomotor skill proficiency are transient. We hypothesized that brief, in situ refresher training will improve chest compression (CC) psychomotor skill retention for bedside providers.

Methods

Nurses completed a baseline skill evaluation of CC quality 6 months after traditional basic life support recertification. Data collected using ResusciAnne with SkillReporter included the following: CC depth, rate, complete release, and correct hand position. Total compliance was defined as 100% CC with depth of 50 mm or greater, rate of 100/min or greater, and more than 90% complete release. After the baseline evaluation, the subjects completed “Rolling Refresher” (RR) CC psychomotor training using audiovisual feedback every 2 to 3 months for 12 months until 30 seconds of CCs fulfilling total compliance criteria was achieved. Chest compression quality evaluations were repeated twice (“RR 6 month” and “RR 12 month” evaluation) after implementation of RR program.

Results

Thirty-seven providers enrolled and completed the baseline evaluation. Mean depth was 36.3 (9.7) mm, and 8% met criteria for depth, 35% for rate, and 5% for total compliance. After RRs were implemented, CC quality improved significantly at RR 6-month evaluation: odds ratio for meeting criteria were the following: depth of 35.1 (95% confidence interval = 2.5496, P = 0.009) and total compliance of 22.3 (95% confidence interval = 2.1239, P = 0.010). There was no difference in CC quality at RR 12-month versus RR 6-month evaluation.

Conclusions

Retention of CC psychomotor skill quality is limited to 6 months after traditional basic life support recertification. Rolling Refresher CC training can significantly improve retention of CC psychomotor skills. Whether CC skills are improved, maintained, or deteriorate after 12 months of Refresher training and optimal frequency of Refreshers is unknown.
Colovesical Fistula Complicating Diverticular Disease: A 14-Year Experience
Authors: Badic Bogdan , Leroux Geoffroy , Thereaux Jérémie , Joumond Aurélien , Gancel Charles H. , Bail Jean P. , Meurette Guillaume
Published: April 2017

Objective:

Colovesical fistulas (CVF) constitute the most common type of spontaneously occurring fistulas associated with diverticular disease. One-stage laparoscopic resection has been shown to be feasible, but studies comparing this approach to open surgery are scarce. The aim of this study was to compare the clinical outcomes of open and laparoscopic surgery for CVF of diverticular origin.

Materials and Methods:

From January 2000 to July 2014, 37 colectomies were performed for diverticular disease–related CVF. Twenty-eight patients who underwent resection and primary anastomosis were divided in 2 groups: the laparoscopic surgery group (group A) and the open surgery group (group B). We have analyzed the following parameters: operative time, complication rate, hospital stay, recurrence, and early mortality rate.

Results:

Groups A and B were comparable in terms of age, sex, diverticulitis episodes, previous abdominal surgery, and body mass index.

The mean duration of surgery was significantly shorter in group B: 175 versus 237 minutes (P=0.011). There was a faster recovery of gastrointestinal transit in group A (2 vs. 13; P=0, 0002). However, there were no significant differences between the groups with respect to serious postoperative morbidity [(Clavien-Dindo scores of 3, 4, and 5) 4 vs. 0; P=0.098)] and with respect to hospital stay (10.5 vs. 9.5 d; P=0.537). There was no recurrence during a median follow-up of 12 months.

Conclusions:

Laparoscopic resection and primary anastomosis should be considered a safe and feasible option for the management of diverticular CVF. Despite progresses in minimally invasive colorectal surgery, the conversion rate and morbidity are still high.
Improving the treatment of infant pain
Authors: Moultrie Fiona , Slater Rebeccah , Hartley Caroline
Published: April 2017

Purpose of review

Pain management presents a major challenge in neonatal care. Newborn infants who require medical treatment can undergo frequent invasive procedures during a critical period of neurodevelopment. However, adequate analgesic provision is infrequently and inconsistently provided for acute noxious procedures because of limited and conflicting evidence regarding analgesic efficacy and safety of most commonly used pharmacological agents. Here, we review recent advances in the measurement of infant pain and discuss clinical trials that assess the efficacy of pharmacological analgesia in infants.

Recent findings

Recently developed measures of noxious-evoked brain activity are sensitive to analgesic modulation, providing an objective quantitative outcome measure that can be used in clinical trials of analgesics.

Noxious stimulation evokes changes in activity across all levels of the infant nervous system, including reflex activity, altered brain activity and behaviour, and long-lasting changes in infant physiological stability. A multimodal approach is needed if we are to identify efficacious and well tolerated analgesic treatments. Well designed clinical trials are urgently required to improve analgesic provision in the infant population.
HiGlass: Web-based Visual Exploration and Analysis of Genome Interaction Maps
Authors: Kerpedjiev Peter , Abdennur Nezar , Lekschas Fritz , McCallum Chuck , Dinkla Kasper , Strobelt Hendrik , Luber Jacob M , Ouellette Scott , Azhir Alaleh , Kumar Nikhil , Hwang Jeewon , Lee Soohyun , Alver Burak H , Pfister Hanspeter , Mirny Leonid A , Park Peter J , Gehlenborg Nils
Published: April 2017

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online athttp://higlass.ioand is also available as a containerized application that can be run on any platform.
Discovery and reduction of nonspecific activities of the major herbicide-resistance gene BAR
Authors: Christ Bastien , Hochstrasser Ramon , Guyer Luzia , Francisco Rita , Aubry Sylvain , Hörtensteiner Stefan , Weng Jing-Ke
Published: April 2017

Herbicide resistance is a major trait of genetically modified (GM) crops. Currently, resistance to phosphinothricin (also known as glufosinate) is the second most widespread genetically engineered herbicide-resistance trait in crops after glyphosate resistance1,2. Resistance to phosphinothricin in plants is achieved by transgenic expression of the bialaphos resistance (BAR) or phosphinothricin acetyltransferase (PAT) genes, which were initially isolated from the natural herbicide bialaphos-producing soil bacteriaStreptomyces hygroscopicusandS. viridochromogenes, respectively3,4. Mechanistically,BARandPATencode phosphinothricin acetyltransferase, which transfers an acetyl group from acetyl coenzyme A (acetyl-CoA) to the α-NH2group of phosphinothricin, resulting in herbicide inactivation1. Although early in vitro enzyme assays showed that recombinant BAR and PAT exhibit substrate preference toward phosphinothricin over the 20 proteinogenic amino acids1, whether transgenic expression of BAR and PAT affects plant endogenous metabolism in vivo was not known. Combining metabolomics, plant genetics, and biochemical approaches, we show that transgenic BAR indeed converts two plant endogenous amino acids, aminoadipate and tryptophan, to their respective N-acetylated products in several plant species examined. We report the crystal structures of BAR, and further delineate structural basis for its substrate selectivity and catalytic mechanism. Through structure-guided protein engineering, we generated several BAR variants that display significantly reduced nonspecific activities compared to its wild-type counterpart. Our results demonstrate that transgenic expression of enzymes as a common strategy in modern biotechnology may render unintended metabolic consequences arisen from enzyme promiscuity. Understanding of such phenomena at the mechanistic level will facilitate better design of maximally insulated systems featuring heterologously expressed enzymes.
Mitochondrial genome variation affects the mutation rate of the nuclear genome inDrosophila melanogaster
Authors: Wolff Jonci N. , Camus M. Florencia , Dowling Damian K. , Rogell Björn
Published: April 2017

Mutations are the raw material for evolutionary change. While the mutation rate has been thought constant between individuals, recent research has shown that poor genetic condition can elevate the mutation rate. Mitonuclear genetic conflict is a potential source of poor genetic condition, and considering the high mutation rate of mitochondrial genomes, there should be ample scope for mitochondrial mutations to interfere with genetic condition, with concomitant effects on the nuclear mutation rate. Moreover, because theory suggests mitochondrial genetic effects will often be male-biased, such effects could be more strongly felt in males than females. Here, by mating irradiated maleDrosophila melanogasterto isogenic females bearing six distinct mitochondrial haplotypes, we tested whether mitochondrial genetic variation affects DNA repair capacity, and whether effects of mutation load on reproductive function are shaped by interactions between sex and mitochondrial haplotype. We found mitochondrial genetic effects on DNA repair, and that the mutational variance of reproductive fitness was higher in males bearing haplotypes characterized by high female fitness. These results suggest that mitochondrial genome variation may affect the mutation rate, and that induced mutations interact more strongly with male than female reproductive function. The potential for haplotype-specific effects on the nuclear mutation rate has broad implications for evolutionary dynamics, such as the accumulation of genetic load, adaptive potential, and the evolution of sexual dimorphism.
Classifying cancer genome aberrations by their mutually exclusive effects on transcription
Authors: Dayton Jonathan B. , Piccolo Stephen R.
Published: April 2017

Background

Malignant tumors are typically caused by a conglomeration of genomic aberrations—including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns. Even though two tumors harbor different genomic aberrations, the transcriptional effects of those aberrations may be similar. These patterns could be used to inform treatment choices.

Methods

We used data from 9300 tumors across 25 cancer types from The Cancer Genome Atlas. We used supervised machine learning to evaluate our ability to distinguish between tumors that had mutually exclusive genomic aberrations in specific genes. An ability to accurately distinguish between tumors with aberrations in these genes suggested that the genes have a relatively different downstream effect on transcription, and vice versa. We compared these findings against prior knowledge about signaling networks and drug responses.

Results

Our analysis recapitulates known relationships in cancer pathways and identifies gene pairs known to predict responses to the same treatments. For example, in lung adenocarcinomas, gene-expression profiles from tumors with somatic aberrations in EGFR or MET were negatively correlated with each other, in line with prior knowledge that MET amplification causes resistance to EGFR inhibition. In breast carcinomas, we observed high similarity between PTEN and PIK3CA, which play complementary roles in regulating cellular proliferation. In a pan-cancer analysis, we found that genomic aberrations in BRAF and VHL exhibit downstream effects that are clearly distinct from other genes.

Conclusion

We show that transcriptional data offer promise as a way to group genomic aberrations according to their downstream effects, and these groupings recapitulate known relationships. Our approach shows potential to help pharmacologists and clinical trialists narrow the search space for candidate gene/drug associations, including for rare mutations, and for identifying potential drug-repurposing opportunities.
RRM domain of ALS/FTD-causing FUS interacts with membrane: an anchor of membraneless organelles to membranes?
Authors: Lu Yimei , Lim Liangzhong , Song Jianxing
Published: April 2017

526-residue FUS functions to self-assemble into reversible droplets/hydrogels, which could be further solidified into pathological fibrils. FUS is composed of N-terminal low-sequence complexity (LC); RNA-recognition motif (RRM) and C-terminal LC domains. FUS belongs to an emerging category of proteins which are capable of forming membraneless organelles in cells via phase separation. On the other hand, eukaryotic cells contain a large network of internal membrane systems. Therefore, it is of fundamental importance to address whether membraneless organelles can interact with membranes. Here we attempted to explore this by NMR HSQC titrations of three FUS domains with gradual addition of DMPC/DHPC bicelle, which mimics the bilayer membrane. We found that both N- and C-terminal LC domains showed no significant interaction with bicelle, but its well-folded RRM domain does dynamically interact with bicelle with an interface opposite to that for binding nucleic acids including RNA and ssDNA. If thisin vitroobservation also occurs in cells, to interact with membrane might represent a mechanism for dynamically organizing membraneless organelles to membranes to facilitate their physiological functions.
The microprotein Minion controls cell fusion and muscle formation
Authors: Zhang Qiao , Vashisht Ajay , O’Rourke Jason , Corbel Stéphane Y. , Moran Rita , Romero Angelica , Miraglia Loren , Zhang Jia , Durrant Eric , Schmedt Christian , Sampath Srinath C. , Sampath Srihari C.
Published: April 2017

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, the functional repertoire of this microproteome remains to be determined1. In skeletal muscle, proper development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process2,3. Here we report the identification of a small ORF encoding an essential skeletal muscle specific microprotein we term Minion (microproteininducer of fusion). Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally with marked reduction in fused muscle fibers. This fusogenic activity is conserved to the human Minion ortholog, previously annotated as a long noncoding RNA. Loss-of-function studies demonstrate that Minion is the factor providing muscle specific fusogenic function for the transmembrane protein Myomaker4. Remarkably, we demonstrate that co-expression of Minion and Myomaker is sufficient to induce rapid cytoskeletal rearrangement and homogeneous cellular fusion, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component program for the induction of mammalian cell fusion, enabling both research and translational applications. Importantly, these data also significantly expand the known functions of smORF-encoded microproteins, an under-explored source of proteomic diversity.
Learning and recognition of tactile temporal sequences by mice and humans
Authors: Bale Michael , Bitzidou Malamati , Pitas Anna , Brebner Leonie , Khazim Lina , Anagnou Stavros , Stevenson Caitlin , Maravall Miguel
Published: April 2017

The world around us is replete with stimuli that unfold over time. When we hear an auditory stream like music or speech or scan a texture with our fingertip, physical features in the stimulus are concatenated in a particular order, and this temporal patterning is critical to interpreting the stimulus. To explore the capacity of mice and humans to learn tactile sequences, we developed a task in which subjects had to recognise a continuous modulated noise sequence delivered to whiskers or fingertips, defined by its temporal patterning over hundreds of milliseconds. GO and NO-GO sequences differed only in that the order of their constituent noise modulation segments was temporally scrambled. Both mice and humans efficiently performed tactile sequence learning. Mouse performance relied mainly on detecting relative changes in noise amplitude over time, whereas humans appeared to have access to more cues, including the duration of noise modulation segments.
Regulation of intercellular TARGET OF MONOPTEROS 7 protein transport in theArabidopsisroot
Authors: Lu Kuan-Ju , De Rybel Bert , van Mourik Hilda , Weijers Dolf
Published: April 2017

Intercellular communication coordinates hypophysis establishment in the Arabidopsis embryo. Previously, TARGET OF MONOPTEROS 7 (TMO7) was reported to be transported to the hypophysis, the founder cell of the root cap, and RNA suppression experiment implicated its function in embryonic root development. However, it remained unclear what protein properties and mechanisms mediate TMO7 protein transport, and what role the movement plays in development. Here, we report that in the post-embryonic root, TMO7 and its close relatives are transported into the root cap through plasmodesmata in a sequence, but not size dependent manner. We also show that nuclear residence is critical for TMO7 transport, and postulate that modification, potentially phosphorylation, labels TMO7 for transport. Additionally, three novel CRISPR/Cas9-inducedtmo7alleles confirmed a role in hypophysis division, but suggest complex redundancies with close relatives in root formation. Finally, we demonstrate that TMO7 transport is biologically meaningful, as local expression partially restores hypophysis division in a plasmodesmatal protein transport mutant. Our study identifies motifs and amino acids critical for TMO7 protein transport and establishes the importance of TMO7 in hypophysis and root development.

Summary Statement

Unique protein motifs, subcellular localization and post-translational modification, rather than protein size regulate plasmodesmatal transport of TMO7 family proteins during Arabidopsis root development.
Feel the way with a vibrotactile compass: Does a navigational aid aid navigation?
Authors: Weisberg Steven M. , Badgio Daniel , Chatterjee Anjan
Published: April 2017

Knowing where north is provides a navigator with invaluable information for learning and recalling a space, particularly in places with limited navigational cues, like complex indoor environments. Although north is effectively used by orienteers, pilots, and military personnel, very little is known about whether non-expert populations can or will use north to create an accurate representation of an indoor space. In the current study, we taught people two non-overlapping routes through a complex indoor environment, with which they were not familiar – a university hospital with few windows and several turns. Along one route, they wore a vibrotactile compass on their arm, which vibrated continuously indicating the direction of north. Along the other route, they were only told where north was at the start of the route. At the beginning, the end, and back at the beginning of each route, participants pointed to well-known landmarks in the surrounding city and campus (external landmarks), and newly-learned landmarks in the hospital (internal landmarks). We found improved performance with the compass only for external landmarks, driven by people’s use of the availability of north to orient these judgments. No such improved orientation occurred for the internal landmarks. These findings reveal the utility of vibrotactile compasses for learning new indoor spaces. We speculate that such cues help users map new spaces onto familiar spaces or to familiar reference frames.
Systematic gene tagging using CRISPR/Cas9 in human stem cells to illuminate cell organization
Authors: Roberts Brock , Haupt Amanda , Tucker Andrew , Grancharova Tanya , Arakaki Joy , Fuqua Margaret A. , Nelson Angelique , Hookway Caroline , Ludmann Susan A. , Mueller Irina A. , Yang Ruian , Horwitz Alan R. , Rafelski Susanne M. , Gunawardane Ruwanthi N.
Published: April 2017

We present a CRISPR/Cas9 genome editing strategy to systematically tag endogenous proteins with fluorescent tags in human inducible pluripotent stem cells. To date we have generated multiple human iPSC lines with GFP tags for 10 proteins representing key cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, lamin B1, non-muscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20. Our genome editing methodology using Cas9 ribonuclear protein electroporation and fluorescence-based enrichment of edited cells resulted in <0.1-24% HDR across all experiments. Clones were generated from each edited population and screened for precise editing. ∼25% of the clones contained precise mono-allelic edits at the targeted locus. Furthermore, 92% (36/39) of expanded clonal lines satisfied key quality control criteria including genomic stability, appropriate expression and localization of the tagged protein, and pluripotency. Final clonal lines corresponding to each of the 10 cellular structures are now available to the research community. The data described here, including our editing protocol, genetic screening, quality control assays, and imaging observations, can serve as an initial resource for genome editing in cell biology and stem cell research.