bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials
Authors: Gallagher J. Christopher , Palacios Santiago , Ryan Kelly A. , Yu Ching-Ray , Pan Kaijie , Kendler David L. , Mirkin Sebastian , Komm Barry S.
Published: July 2016

Objective:

Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials.

Methods:

Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region.

Results:

There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores −1.05 and −0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001).

Conclusions:

Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.
Jeryl-Lynn Mumps Vaccine-Derived Parotitis Diagnosed in the Setting of a Recent Mumps Outbreak
Authors: Coster Laura O'Bryan , Mohanraj B. Sharmila , Kessler Roanna , Timpone Joseph , Kumar Princy
Published: July 2016

This report details the diagnosis of Jeryl-Lynn vaccine-derived parotitis in a medical student after receiving the measles-mumps-rubella vaccine. Diagnostic verification of mumps vaccine-induced disease was a priority given a recent mumps outbreak affecting 13 students in the undergraduate university and another medical student at the same university's affiliated medical school. Ultimately, genotypic analysis of the medical student's buccal mumps polymerase chain reaction sample confirmed vaccine-induced disease.
Postneurosurgical Meningitis Due to Haemophilus influenzae Type D
Authors: Urich Ryan M. , Lee Samuel A.
Published: July 2016

Postsurgical meningitis is an uncommon but serious postoperative complication of intracranial surgery. Central nervous system infection due to Haemophilus influenzae type D is exceedingly rare. We describe a case of postsurgical meningitis due to H. influenza type D in an immunocompetent patient after transphenoidal pituitary adenoma resection.
Reporting of cross-over clinical trials of analgesic treatments for chronic pain: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations
Authors: Gewandter Jennifer S. , McDermott Michael P. , McKeown Andrew , Hoang Kim , Iwan Katarzyna , Kralovic Sarah , Rothstein Daniel , Gilron Ian , Katz Nathaniel P. , Raja Srinivasa N. , Senn Stephen , Smith Shannon M. , Turk Dennis C. , Dworkin Robert H.
Published: July 2016

Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided.
Is alcohol consumption related to likelihood of reporting chronic widespread pain in people with stable consumption? Results from UK biobank
Authors: Beasley Marcus J. , Macfarlane Tatiana V. , Macfarlane Gary J.
Published: July 2016

Studies have suggested that alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40 to 69 years, registered at medical practices nationwide. Participants provided detailed information on health and lifestyle factors including pain and alcohol consumption. Total units consumed per week were calculated for current drinkers. Information was also collected on changes in alcohol consumption and reasons for such changes. Analysis was performed with logistic regression expressed as odds ratios (ORs) with 95% confidence intervals, then adjusted for a large number of potential confounding factors (adjORs). In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (nondrinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% confidence intervals [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females, there was a decrease in the proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (nondrinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption because of health concerns, after adjustment for potential confounding factors.
Gastrointestinal Dysfunction and Neuropathologic Correlations in Parkinson Disease
Authors: Mrabet Saloua , Ben Ali Nadia , Achouri Afef , Dabbeche Radhouene , Najjar Taoufik , Haouet Slim , Belal Samir
Published: July 2016

Introduction:

Recently, an increasing interest to nonmotor symptoms of Parkinson disease (PD) has shown. Gastrointestinal dysfunction is a prominent nonmotor manifestation of PD and precedes motor symptoms for several years. Neuropathologic studies show early accumulation of α-synuclein (α-SYN) in Lewy neurites and Lewy body in the enteric nervous system (ENS) and dorsal motor nucleus of the vagus in PD. Our study aims to investigate relationship between α-SYN deposition in ENS and gastrointestinal dysfunction in PD.

Materials and Methods:

We conducted a study in Neurology Department of Charles Nicolle Hospital of Tunis during 2 years (2013 to 2014) including PD patients. Clinical data were analyzed. Digestive endoscopy with biopsies of upper digestive tract (UDT) and immunohistochemistry study were performed.

Results:

Thirty patients (16♂/14♀) and 13 (7♂/6♀) controls were included. Average age was 65 years for patients and 63.5 years for controls. Gastrointestinal symptoms were the most frequent nonmotor symptoms occurring in 73%. Endoscopy showed motor dysfunction of upper digestive tract in 5 patients. Lesion load in α-SYN was significantly correlated with frequency and severity of gastrointestinal dysfunction and PD motor disability.

Conclusions:

Gastrointestinal disturbances are frequent in PD. ENS’s synucleinopathy could entirely explain pathophysiology of digestive dysfunction and is correlated with severity of gastrointestinal symptoms in PD. Biopsies may show α-SYN aggregates in immunoreactive Lewy neurites in the submucosal and myenteric plexus. Thus, endoscopic and immunohistochemical exploration of ENS may be a biomarker for Parkinson enteropathy and for PD overall.
Dilation of Pediatric Eosinophilic Esophagitis
Authors: Menard‐Katcher Calies , Furuta Glenn T. , Kramer Robert E.
Published: July 2016

Objectives:

Although several studies report on the experience with adult eosinophilic esophagitis (EoE)–related stricture, outcomes for pediatric patients with EoE–associated fibrostenosis and stricture is more limited. To address this, we aim to identify the adverse event (AE) rate and short‐term outcomes of the largest reported cohort of children with EoE to undergo esophageal dilation for management of symptomatic esophageal narrowing.

Methods:

A retrospective assessment of all children, 18 years and younger, who underwent esophageal dilation at an academic children's hospital during a 5‐year period was conducted. Clinical, endoscopic, histologic, and outcomes of dilation were extracted from the medical record. AEs were captured within a standardized endoscopic AE database. Grade 2 AEs (requiring unanticipated medical intervention) were termed significant. Dilation‐related events were compared between patients with EoE, without EoE, and those undergoing standard upper endoscopy.

Results:

Of the 451 total dilations, 68 dilations were performed in 40 EoE patients (mean age 13.8 years, standard deviation 3.3 years [4.6–18.9 years]). Forty‐three percent (17/40) had repeat dilation during the study period. Dilation‐related grade 2 AE rates in EoE and in non‐EoE patients were 2.9% and 3.1%, respectively (P > 0.5). Chest pain (any grade AE) was reported in 14.7% of EoE dilations. No significant associations were found between postprocedural pain and dilation method, final dilator size, medical therapy, or esophageal eosinophilia. No perforations or significant hemorrhage were reported.

Conclusions:

We conclude that dilation can be performed safely in children with EoE. In the appropriate clinical setting, cautious dilation may be considered in the management of fibrostenotic EoE.
Gender and Age Differences in Trauma and PTSD Among Dutch Treatment-Seeking Police Officers
Authors: van der Meer Christianne A.I. , Bakker Anne , Smit Annika S. , van Buschbach Susanne , den Dekker Melissa , Westerveld Gré J. , Hutter Renée C. , Gersons Berthold P.R. , Olff Miranda
Published: July 2016

Little is known about how age and gender are associated with posttraumatic stress disorder (PTSD) symptoms and traumatic experiences in treatment-seeking police offers. In this study, we examined 967 diagnostic files of police officers seeking treatment for PTSD. Six hundred twelve (63%) of the referred police officers were diagnosed with PTSD (n = 560) or partial PTSD (n = 52). Police officers reported on average 19.5 different types of traumatic events (range 1–43). Those who experienced a greater variety of traumatic events suffered from more PTSD symptoms. Also, women reported more often direct life-threatening or private events as their index trauma than men and suffered from more PTSD symptoms than their male colleagues. Results indicate that police officers experience a considerable number of different traumatic events, which is significantly associated with PTSD symptoms. The results highlight the importance of early detection of PTSD symptoms in the police force.
Neurocognitive Phenotypes in Severe Childhood Psychiatric Disorders
Authors: Kavanaugh Brian C. , Dupont-Frechette Jennifer A. , Tellock Perrin P. , Maher Isolde D. , Haisley Lauren D. , Holler Karen A.
Published: July 2016

This study investigated the presence of potential neurocognitive phenotypes within a severe childhood psychiatric sample. A medical chart review was conducted for 106 children who received a neuropsychological evaluation during children’s psychiatric inpatient program hospitalization. A hierarchical cluster analysis was conducted to identify distinct clinical clusters based on neurocognitive measures. Cluster analysis identified four distinct clusters, subsequently labeled neurocognitive phenotypes: “intact cognition” (27%), “global dysfunction” (20%), “organization/planning” (21%), and “inhibition-memory” (32%). Significant differences were identified in history of legal involvement and antipsychotic medications at hospital admission. Differences between none-minimal and moderate-high neurocognitive dysfunction were identified in age, amount of diagnoses and antipsychotic medications at admission, and hospital length of stay. Current findings provide preliminary evidence of underlying neurocognitive phenotypes within severe childhood psychiatric disorders. Findings highlight the importance of neuropsychological evaluation in the treatment of childhood psychiatric disorders.
Learning Needs Assessment
Authors: Pilcher Jobeth
Published: July 2016

An accurate assessment of what participants need to learn is a crucial initial step in planning educational activities. Methods for assessing learner needs can include reviewing the literature, benchmarking, reviewing documents, seeking learner input, and multiple other data collection methods. The purpose of this article is to provide nursing professional development practitioners with an overview of learning needs assessments, including definitions, categories, measurement tools, and steps to perform the assessment.
Measuring Return on Investment for Professional Development Activities:
Authors: Opperman Cathleen , Liebig Debra , Bowling Judith , Johnson Carol Susan , Harper Mary
Published: July 2016

What is the return on investment (ROI) for the time and resources spent for professional development activities? This is Part 2 of a two-part series to report findings and demonstrate how financial analysis of educational activities can drive decision-making. The resources consumed for professional development activities need to be identified and quantified to be able to determine the worth of such activities. This article defines terms and formulas for financial analysis for nursing professional development practitioners to use in analysis of their own programs. Three fictitious examples of common nursing professional development learning activities are provided with financial analysis. This article presents the “how to” for the busy practitioner.
Introduction of the Engaged Feedback Reflective Inventory During a Preceptor Training Program
Authors: Rosa William , Santos Sarla
Published: July 2016

The purpose of this article is to explore how effective communication, in the form of engaged feedback, may aid in the self-care of the preceptor and an improved working relationship between preceptor and orientee. The application of the Engaged Feedback Reflective Inventory offers opportunity for both new and seasoned preceptors to discover growth opportunities in the realms of effective communication and self-care. Further research needs to be conducted in order to assess improved outcomes post training.
Modulation of PD-L1 and CD8 Activity in Idiopathic and Infectious Chronic Inflammatory Conditions
Authors: Mezache Louisa , Magro Cynthia , Hofmeister Craig , Pichiorri Flavia , Sborov Douglas , Nuovo Gerard J.
Published: July 2016

Programmed death-ligand 1 (PD-L1) can reduce the immune response by inhibiting CD8 T-cell proliferation and cytotoxic activity. We studied a series of human viral (molloscum, human papillomavirus, herpes simplex, cytomegalovirus, Epstein-Barr virus, smallpox) and bacterial infections (Helicobacter pylori) for the in situ expression of PD-L1, mononuclear cell infiltration, and CD8 activity and compared this to noninfectious idiopathic inflammatory conditions to better define which immune responses may be more highly correlated with an infectious agent. Each viral and bacterial infection showed an increased PD-L1 expression that was most prominent in the mononuclear cell/CD8+ infiltrate surrounding the infection. However, the CD8 cells were mostly quiescent as evidenced by the low Ki67 index and minimal granzyme expression. Using a melanoma mouse model, acute reovirus infection increased PD-L1 expression, but decreased CD8 cytotoxic activity and Treg (FOXP3) cell numbers. In comparison, idiopathic noninfectious chronic inflammatory processes including lichen sclerosis, eczema, Sjogren’s disease, and ulcerative colitis showed a comparable strong PD-L1 expression in the mononuclear cell infiltrates but much greater Treg infiltration. However, this strong immunosuppressor profile was ineffective as evidenced by strong CD8 proliferation and granzyme expression. These data suggest that viral and bacterial infections induce a PD-L1 response that, unlike noninfectious chronic inflammatory conditions, dampens the activity of the recruited CD8 cells which, in turn, may enhance the ability of anti-PD-L1 therapy to eliminate the infectious agent.
Clinicopathologic Characteristics of Solid Papillary Carcinoma of the Breast
Authors: Tan Benjamin Yongcheng , Thike Aye Aye , Ellis Ian O. , Tan Puay Hoon
Published: July 2016

Solid papillary carcinoma (SPC) of the breast is defined as a “distinctive form of papillary carcinoma characterized by closely apposed expansive, cellular nodules.” This uncommon tumor frequently demonstrates neuroendocrine differentiation. SPCs are staged as in situ tumors, except those that exhibit jagged borders within desmoplastic stroma, or if accompanied by conventional invasive carcinoma, which is separately graded and staged. In this study, we review the immunomorphologic characteristics of SPCs diagnosed at our institution, with a view toward elucidating points of distinction from other mammary carcinomas that manifest neuroendocrine differentiation. A total of 250 cases of in situ and invasive carcinomas with immunohistochemically documented neuroendocrine differentiation, spanning 12 years, were retrieved from the records of the Department of Pathology, Singapore General Hospital. Morphologic review identified 108 (43.2%) cases of SPC (in situ and/or invasive) among this group of tumors. Tumors with SPC components were significantly associated with estrogen receptor, progesterone receptor, and chromogranin A expression, spindled tumor morphology, and older patient age (above median age). In addition, invasive carcinomas with SPC components were more likely to be of smaller size (≤20 mm), low grade (grade 1), and to occur in older patients (above median age), compared with cases of invasive carcinoma lacking an SPC component. In situ SPCs were significantly associated with mucin production and demonstrated improved disease-free survival over cases of conventional ductal carcinoma in situ with neuroendocrine differentiation. Presence of an SPC pattern is associated with favorable clinicopathologic characteristics, with in situ SPCs demonstrating improved disease-free survival, emphasizing the importance of accurately diagnosing this uncommon tumor.
Results of Endoscopic and Surgical Fistula Treatment in Esophagointestinal Anastomosis After Gastrectomy
Authors: Miłek Tomasz , Myrcha Piotr , Ciostek Piotr
Published: July 2016

Introduction:

Intestinal fistulas occur in 4% to 8% of cases of upper gastrointestinal tract surgery. Until now, this type of surgery has been the standard for treating fistulas in esophagointestinal anastomosis. The use of stents and hemoclips is still controversial, but an increasing number of publications have been presenting good results with this type of treatment.

Objective:

The objective of the study was to investigate the outcome of endoscopic and surgical treatment of fistulas in esophagointestinal anastomosis after gastrectomy.

Materials and Methods:

Fistulas in esophagointestinal anastomoses were observed in 23 patients (4.8%) over an 18-year period. The indications for endoscopic treatment were small (<50 mL/d) and large (>50 mL/d) fistulas in patients with no symptoms of peritonitis or abscess, who were treated with implantation of a covered stent.

Surgical intervention was carried out for large fistulas that resulted in peritonitis and complicated gangrene of margins and/or abscesses.

Results:

Four subjects were treated endoscopically with hemoclips, resulting in 50% technical and clinical success. We implanted stents in 12 patients. Technical success was achieved in all patients; yet, permanent closure of the fistula was reported in 8 subjects (66%). Thirty-three percent of patients were operated upon for fistulas. We reported 4 deaths in this group.

Conclusions:

The use of hemoclips in the treatment of small fistulas and of self-expandable covered stents in the treatment of medium and large fistulas is an effective method that shortens the hospitalization period and accelerates the introduction of oral nutrition while reducing the number of fatal complications.
Advantages and Disadvantages of 1-Incision, 2-Incision, 3-Incision, and 4-Incision Laparoscopic Cholecystectomy: A Workflow Comparison Study
Authors: Bartnicka Joanna , Zietkiewicz Agnieszka A. , Kowalski Grzegorz J.
Published: July 2016

A comparison of 1-port, 2-port, 3-port, and 4-port laparoscopic cholecystectomy techniques from the point of view of workflow criteria was made to both identify specific workflow components that can cause surgical disturbances and indicate good and bad practices. As a case study, laparoscopic cholecystectomies, including manual tasks and interactions within teamwork members, were video-recorded and analyzed on the basis of specially encoded workflow information. The parameters for comparison were defined as follows: surgery time, tool and hand activeness, operator’s passive work, collisions, and operator interventions. It was found that 1-port cholecystectomy is the worst technique because of nonergonomic body position, technical complexity, organizational anomalies, and operational dynamism. The differences between laparoscopic techniques are closely linked to the costs of the medical procedures. Hence, knowledge about the surgical workflow can be used for both planning surgical procedures and balancing the expenses associated with surgery.
Laparoscopic Spigelian Hernia Repair: A Systematic Review
Authors: Barnes Thomas G. , McWhinnie Douglas L.
Published: July 2016

Purpose:

Spigelian hernias (SHs) account for 1% to 2% of abdominal wall hernias. Traditionally they have been repaired using an open technique. Since 1992, laparoscopic methods have become increasingly popular with various techniques being described in the literature. This systematic review aims to represent the current trends in laparoscopic repair of SHs.

Materials and Methods:

The databases MEDLINE and EMBASE were searched for appropriate terms regarding SH repair. Papers describing laparoscopic repair of SH were included.

Results:

Fifty articles were identified for the final review. No randomized controlled trials comparing laparoscopic techniques were identified. Two hundred thirty-seven SHs were repaired by various techniques. Intraperitoneal onlay mesh technique was the most popular repair method with minimal complications and recurrences reported in all techniques.

Conclusions:

There are a number of laparoscopic techniques available to the surgeon repairing a SH. Overall, laparoscopic repair of the SH is a safe and acceptable method.
Impact of Laparoscopic Lens Contamination in Operating Theaters: A Study on the Frequency and Duration of Lens Contamination and Commonly Utilized Techniques to Maintain Clear Vision
Authors: Yong Nathanael , Grange Philippe , Eldred-Evans David
Published: July 2016

Introduction:

In laparoscopy, contamination of the distal lens is problematic. Not only a cause of frustration, repeatedly cleaning the laparoscope takes up significant time and disrupts the operative flow. Our study aims to explore and describe quantitatively this particular issue within the operating theaters of a major teaching hospital.

Materials and Methods:

We recorded data assessing the occurrence of impaired vision on the screen display and quantified the occurrence, duration, and modality of cleaning events. Data were recorded on a time-line sheet and collected for basic quantitative analysis as reported below. A brief interview with the surgeons was carried out at the end of each procedure.

Results:

A total of 64 hours of laparoscopy covering 25 procedures in 4 surgical disciplines were observed. The study found that 56% of the operation was performed with a clear display, while 37% of the time was spent impaired vision. Seven percent of the operation was spent cleaning the distal lens. The interviews recorded a unison sense of frustration and safety concerns regarding lens contamination.

Conclusions:

Our observational study demonstrates that one third of the duration of a laparoscopic procedure is performed without perfectly clear display. The suboptimal display during an operation is similar to that of driving with a dirty windshield and having to step out of the car to clean it before continuing with the journey. The disruption to operative flow is transcribed as frustration felt by surgeons when display is compromised and having to clean the lens. However, the economical impact of cleaning the lens during the operation remains to be demonstrated.
How to Quantify Recovery After Laparoscopic Adrenalectomy: An Assessment of Patient-reported Health-related Quality of Life
Authors: Dovirak Ostap , Mao Jialin , Taylor Kimberly , Chang Peter , Wagner Andrew A.
Published: July 2016

Introduction and Objective:

Minimally invasive approaches to adrenal surgery were adopted in an attempt to reduce surgical morbidity. Despite the widespread use, few studies objectively evaluate health-related quality of life (HRQOL) in patients undergoing laparoscopic adrenalectomy (LA). We assessed patients’ health status and recovery after LA with the use of validated questionnaires.

Methods:

Patients seen in urology clinic for evaluation of adrenal surgery were enlisted in our prospective, patient-reported, HRQOL study assessing postoperative recovery. HRQOL was measured using Convalescence And Recovery Evaluation (CARE) and Short Form-12 questionnaires administered before surgery and at 2, 4, 8, 12 weeks and annually after surgery. All operations were performed using a laparoscopic transperitoneal approach by a single fellowship-trained surgeon.

Results:

A total of 30 patients who met study inclusion criteria from July 2009 to November 2014 were included in our evaluation. Mean patient age was 53 years. Tumor size ranged from 2.0 to 5.5 cm and consisted of benign lesions, adrenal metastasis, and 1 adrenocortical carcinoma. Mean operative time was 98 minutes and median estimated blood loss was 50 mL. Median length of hospital stay was 1 day. Quality of life reflected by the CARE survey was impacted at 2 weeks postoperative and returned to baseline after 4 weeks. Pain and activity domains of CARE showed a significant decrease from baseline status. Physical component summary of Short Form-12 questionnaire supported the finding of negative impact of surgery on activity level within first 4 weeks of recovery.

Conclusions:

Despite minimally invasive approach, patients undergoing LA may require about 4 weeks to return to baseline activity, gastrointestinal, and pain status.
Staple-Line Reinforcement of the Duodenal Stump With Intracorporeal Lembert’s Sutures in Laparoscopic Distal Gastrectomy With Roux-en-Y Reconstruction for Gastric Cancer
Authors: Inoue Kentaro , Michiura Taku , Fukui Junichi , Mukaide Hiromi , Ozaki Takashi , Miki Hirokazu , Kobayashi Toshinori , Oishi Masaharu , Inada Ryo , Matsumoto Tomoko , Yamada Masanori , Yanagimoto Hiroaki , Kim Songtae , Satoi Sohei , Kaibori Masaki , Kon Masanori , Hamada Madoka
Published: July 2016

Purpose:

We report a duodenal stump reinforcement procedure in laparoscopic distal gastrectomy with Roux-en-Y reconstruction.

Methods:

We retrospectively reviewed the data of 223 patients who underwent laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. We compared 2 groups: group NR (not reinforced, n=102, June 2009 to December 2011) when we did not perform reinforcement of the duodenal stump, and group R (reinforced, n=121, January 2012 to July 2014) when we did the reinforcement. The duodenum was divided with an endoscopic linear stapler. In group R, the duodenal staple line was reinforced by hand-sewn Lembert’s sutures.

Results:

There were no significant differences between group NR and R in patients’ characteristics. Duodenal stump leakage occurred in 2 patients in group NR (2.0%). By contrast, in R group, no patients had duodenal stump leakage or fistula.

Conclusions:

Duodenal stump leakage can be avoided by using reinforcement with Lembert’s sutures.
Evolutionary transitions during RNA virus experimental evolution
Authors: Elena Santiago F.
Published: July 2016

In their search to understand the evolution of biological complexity, John Maynard Smith and Eörs Szathmáry put forward the notion of major evolutionary transitions as those in which elementary units get together to generate something new, larger and more complex. The origins of chromosomes, eukaryotic cells, multicellular organisms, colonies and, more recently, language and technological societies are examples that clearly illustrate this notion. However, a transition may be considered as anecdotal or as major depending on the specific level of biological organization under study. In this contribution, I will argue that transitions may also be occurring at a much smaller scale of biological organization: the viral world. Not only that, but also that we can observe in real time how these major transitions take place during experimental evolution. I will review the outcome of recent evolution experiments with viruses that illustrate four major evolutionary transitions: (i) the origin of a new virus that infects an otherwise inaccessible host and completely changes the way it interacts with the host regulatory and metabolic networks, (ii) the incorporation and loss of genes, (iii) the origin of segmented genomes from a non-segmented one, and (iv) the evolution of cooperative behaviour and cheating between different viruses or strains during co-infection of the same host.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
The major synthetic evolutionary transitions
Authors: Solé Ricard
Published: July 2016

Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Metagenomic data-mining reveals contrasting microbial populations responsible for trimethylamine formation in human gut and marine ecosystems
Authors: Jameson Eleanor , Doxey Andrew C. , Airs Ruth , Purdy Kevin J. , Murrell J. Colin , Chen Yin
Published: July 2016

Existing metagenome datasets from many different environments contain untapped potential for understanding metabolic pathways and their biological impact. Our interest lies in the formation of trimethylamine (TMA), a key metabolite in both human health and climate change. Here, we focus on bacterial degradation pathways for choline, carnitine, glycine betaine and trimethylamine N-oxide (TMAO) to TMA in human gut and marine metagenomes. We found the TMAO reductase pathway was the most prevalent pathway in both environments. Proteobacteria were found to contribute the majority of the TMAO reductase pathway sequences, except in the stressed gut, where Actinobacteria dominated. Interestingly, in the human gut metagenomes, a high proportion of the Proteobacteria hits were accounted for by the genera Klebsiella and Escherichia. Furthermore Klebsiella and Escherichia harboured three of the four potential TMA-production pathways (choline, carnitine and TMAO), suggesting they have a key role in TMA cycling in the human gut. In addition to the intensive TMAO–TMA cycling in the marine environment, our data suggest that carnitine-to-TMA transformation plays an overlooked role in aerobic marine surface waters, whereas choline-to-TMA transformation is important in anaerobic marine sediments. Our study provides new insights into the potential key microbes and metabolic pathways for TMA formation in two contrasting environments.
Editing of the urease gene by CRISPR-Cas in the diatomThalassiosira pseudonana
Authors: Hopes Amanda , Nekrasov Vladimir , Kamoun Sophien , Mock Thomas
Published: July 2016

Background: CRISPR-Cas is a recent and powerful edition to the molecular toolbox which allows programmable genome editing. It has been used to modify genes in a wide variety of organisms, but only two alga to date. Here we present a methodology to edit the genome ofT. pseudonana, a model centric diatom with both ecological significance and high biotechnological potential, using CRISPR-Cas.

Results: A single construct wa assembled using Golden Gate cloning. Two sgRNAs were used to introduce a precise 37nt deletion early in the coding region of the urease gene. A high percentage of bi-allelic mutations (≤ 61.5%) were observed in clones with the CRISPR-Cas construct. Growth of bi-allelic mutants in urea led to a significant reduction in growth rate and cell size compared to growth in nitrate.

Conclusions: CRISPR-Cas can precisely and efficiently edit the genome ofT. pseudonana. The use of Golden Gate cloning to assemble CRISPR-Cas constructs gives additional flexibility to the CRISPR-Cas method and facilitates modifications to target alternative genes or species.
A Multi-Scale Computational Model of the effects of TMS on Motor Cortex
Authors: Seo Hyeon , Schaworonkow Natalie , Jun Sung Chan , Triesch Jochen
Published: July 2016

The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different cell types in motor cortex due to transcranial magnetic stimulation. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict detailed neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to predict activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also predicts differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of corctial pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.
The haplotype-resolved genome sequence of hexaploidIpomoea batatasreveals its evolutionary history
Authors: Yang Jun , Moeinzadeh M-Hossein , Kuhl Heiner , Helmuth Johannes , Xiao Peng , Liu Guiling , Zheng Jianli , Sun Zhe , Fan Weijuan , Deng Gaifang , Wang Hongxia , Hu Fenhong , R Fernie Alisdair , Timmermann Bernd , Zhang Peng , Vingron Martin
Published: July 2016

Although the sweet potato,Ipomoea batatas, is the seventh most important crop in the world and the fourth most significant in China, its genome has not yet been sequenced. The reason, at least in part, is that the genome has proven very difficult to assemble, being hexaploid and highly polymorphic; it has a presumptive composition of two B1and four B2component genomes (B1B1B2B2B2B2). By using a novel haplotyping method based on de novo genome assembly, however, we have produced a half haplotype-resolved genome from ∼267Gb of paired-end sequence reads amounting to roughly 60-fold coverage. By phylogenetic tree analysis of homologous chromosomes, it was possible to estimate the time of two whole genome duplication events as occurring about 525,000 and 341,000 years ago. Our analysis also identified many clusters of genes for specialized compounds biosynthesis in this genome. This half haplotype-resolved hexaploid genome represents the first successful attempt to investigate the complexity of chromosome sequence composition directly in a polyploid genome, using direct sequencing of the polyploid organism itself rather than of any of its simplified proxy relatives. Adaptation and application of our approach should provide higher resolution in future genomic structure investigations, especially for similarly complex genomes.
Calculating Biological Module Enrichment or Depletion and Visualizing Data on Large-scale Molecular Maps with ACSNMineR and RNaviCell R packages
Authors: Deveau Paul , Barillot Emmanuel , Boeva Valentina , Zinovyev Andrei , Bonnet Eric
Published: July 2016

Biological pathways or modules represent sets of interactions or functional relationships occurring at the molecular level in living cells. A large body of knowledge on pathways is organized in public databases such as the KEGG, Reactome, or in more specialized repositories, such as the Atlas of Cancer Signaling Network (ACSN). All these open biological databases facilitate analyses, improving our understanding of cellular systems. We hereby describe the R packageACSNMineRfor calculation of enrichment or depletion of lists of genes of interest in biological pathways. ACSNMineR integrates ACSN molecular pathways, but can use any molecular pathway encoded as a GMT file, for instance sets of genes available in the Molecular Signatures Database (MSigDB). We also present the R packageRNaviCell, that can be used in conjunction withACSNMineRto visualize different data types on web-based, interactive ACSN maps. We illustrate the functionalities of the two packages with biological data taken from large-scale cancer datasets.
Strehler-Mildvan correlation is a degenerate manifold of Gompertz fit
Authors: Tarkhov Andrei E. , Menshikov Leonid I. , Fedichev Peter O.
Published: July 2016

Gompertz empirical law of mortality is often used in practical research to parametrize survival fraction as a function of age with the help of just two quantities: the Initial Mortality Rate (IMR) and the Gompertz exponent, inversely proportional to the Mortality Rate Doubling Time (MRDT). The IMR is often found to be inversely related to the Gompertz exponent, which is the dependence commonly referred to as Strehler-Mildvan (SM) correlation. In this paper, we address fundamental uncertainties of the Gompertz parameters inference from experimental Kaplan-Meier plots and show, that a least squares fit often leads to an ill-defined non-linear optimization problem, which is extremely sensitive to sampling errors and the smallest systematic demographic variations. Therefore, an analysis of consequent repeats of the same experiments in the same biological conditions yields the whole degenerate manifold of possible Gompertz parameters. We find that whenever the average lifespan of species greatly exceeds MRDT, small random variations in the survival records produce large deviations in the identified Gompertz parameters along the line, corresponding to the set of all possible IMR and MRDT values, roughly compatible with the properly determined value of average lifespan in experiment. The best fit parameters in this case turn out to be related by a form of SM correlation. Therefore, we have to conclude that the combined property, such as the average lifespan in the group, rather than IMR and MRDT values separately, may often only be reliably determined via experiments, even in a perfectly homogeneous animal cohort due to its finite size and/or low age-sampling frequency, typical for modern high-throughput settings. We support our findings with careful analysis of experimental survival records obtained in cohorts ofC. elegansof different sizes, in control groups and under the influence of experimental therapies or environmental conditions. We argue that since, SM correlation may show up as a consequence of the fitting degeneracy, its appearance is not limited to homogeneous cohorts. In fact, the problem persists even beyond the simple Gompertz mortality law. We show that the same degeneracy occurs exactly in the same way, if a more advanced Gompertz-Makeham aging model is employed to improve the modeling. We explain how SM type of relation between the demographic parameters may still be observed even in extremely large cohorts with immense statistical power, such as in human census datasets, provided that systematic historical changes are weak in nature and lead to a gradual change in the mean lifespan.
The evolution of genetic bandwagoning
Authors: Solon Idan S.
Published: July 2016

Background

In separate literatures, biologists have marshaled theoretical and empirical support for theories that a variant can be selected to (1) induce suicide by moribund or otherwise stressed holders; (2) induce suicide by a holder with low productive or reproductive potential; (3) impose senescence upon a chronologically old holder; and (4) reduce the yield of a holder with low genetic heterozygosity. High stress, moribundity, low productive and reproductive potential, high chronological age, and low genetic heterozygosity all indicate the holder has a relative paucity of advantageous genetic variants in acquiring prey, territory, and mates or surviving predators and parasites. Therefore, an unappreciated commonality between these theories is that a variant can be selected that reduces the fitness of a holder of low genetic quality.

Here, I argue that a variant can be selected that reduces its holder’s fitness in response to not just these indications but also other indications of low genetic quality. The fitness losses induced by the variant in low-quality individuals allow fitness gains for nearby individuals, some of which hold a copy of the variant. The variant gains frequency by hitchhiking along with (“jumping on the bandwagon” of) higher-quality individuals (and their lineages) that have copies of the variant; therefore, it is called a “bandwagoning” variant.

Questions

What parameter values (e.g., population quantity, relatedness, heritability of reproductive success) allow natural selection of genetic bandwagoning?

Features of the model

The model is an individual-based Moran process. Each individual’s quality value is randomly chosen at birth from a normal distribution that has a mean equal to the quality value of its parent.

Ranges of parameters

Total population quantity varied from 50 to 500. Assortment (“relatedness”) in the population varied from .05 to .15. Recorded values for the heritability of reproductive success varied from .024 to .132.

Conclusions

Natural selection of genetic bandwagoning can occur even when values for population quantity, relatedness, and heritability of reproductive success are low enough to be in line with reported values for humans and other species. Therefore, genetic bandwagoning theory can explain why indications of an organism’s low genetic quality induce behavior by, or biological processes within, that organism that reduce that organism’s fitness.
The Origin of Coupled Chloride and Proton Transport in a Cl−/H+Antiporter
Authors: Lee Sangyun , Mayes Heather B. , Swanson Jessica M. J. , Voth Gregory A.
Published: July 2016

The ClC family of transmembrane proteins functions throughout nature to control the transport of Cl−ions across biological membranes. ClC-ec1 fromEscherichia coliis an antiporter, coupling the transport of Cl−and H+ions in opposite directions and driven by the concentration gradients of the ions. Despite keen interest in this protein, the molecular mechanism of the Cl−/H+coupling has not been fully elucidated. Here, we have used multiscale simulation to help identify the essential mechanism of the Cl−/H+coupling. We find that the highest barrier for proton transport (PT) from the intra- to extracellular solution is attributable to a chemical reaction—the deprotonation of glutamic acid 148 (E148). This barrier is significantly reduced by the binding of Cl−in the “central” site (Cl−cen), which displaces E148 and thereby facilitates its deprotonation. Conversely, in the absence of Cl−cenE148 favors the “down” conformation, which results in a much higher cumulative rotation and deprotonation barrier that effectively blocks PT to the extracellular solution. Thus, the rotation of E148 plays a critical role in defining the Cl−/H+coupling. As a control, we have also simulated PT in the ClC-ec1 E148A mutant to further understand the role of this residue. Replacement with a non-protonatable residue greatly increases the free energy barrier for PT from E203 to the extracellular solution, explaining the experimental result that PT in E148A is blocked whether or not Cl−cenis present. The results presented here suggest both how a chemical reaction can control the rate of PT and also how it can provide a mechanism for a coupling of the two ion transport processes.