bluuebunny/crossref_metadata_2025 huggingface dataset:
POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas
Authors: Rosner Guy , Gluck Nathan , Carmi Shai , Bercovich Dani , Fliss-Issakov Naomi , Ben-Yehoyada Merav , Aharon-Caspi Sivan , Kellerman Efrat , Strul Hana , Shibolet Oren , Kariv Revital
Published: August 2018

BACKGROUND:

Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized.

OBJECTIVE:

The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers.

DESIGN:

This study is a comparison of genetic and clinical data from affected and control groups.

SETTINGS:

The study was conducted at a high-volume tertiary referral center.

PATIENTS:

The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas.

MAIN OUTCOME MEASURES:

Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed.

RESULTS:

Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p < 0.001). Eight of the 11 mutation carriers were Ashkenazi Jews carrying the same POLD1 mutation (V759I), implicating it as a possible low-to-moderate risk founder mutation. Phenotype of mutation carriers was notable for age under 50 at diagnosis, a propensity toward left-sided colorectal cancer, and extracolonic tumors (64%, 100%, and 27% of cases).

LIMITATIONS:

The study cohort was limited by its relatively small size.

CONCLUSIONS:

Germline mutations in POLD1 and POLE were found to be relatively frequent in our Jewish cohorts. Further studies are needed to clarify the importance of POLD1 and POLE mutations and to define the most suitable surveillance program for Jewish and other POLD1 and POLE mutation carriers. See Video Abstract at http://links.lww.com/DCR/A658.
Enhanced Recovery Protocols for Adults Undergoing Colorectal Surgery: A Systematic Review and Meta-analysis
Authors: Greer Nancy L. , Gunnar William P. , Dahm Philipp , Lee Alice E. , MacDonald Roderick , Shaukat Aasma , Sultan Shahnaz , Wilt Timothy J.
Published: August 2018

BACKGROUND:

Enhanced surgical recovery protocols are designed to reduce hospital length of stay and health care costs.

OBJECTIVE:

This study aims to systematically review and summarize evidence from randomized and controlled clinical trials comparing enhanced recovery protocols versus usual care in adults undergoing elective colorectal surgery with emphasis on recent trials, protocol components, and subgroups for surgical approach and colorectal condition.

DATA SOURCES:

MEDLINE from 2011 to July 2017; reference lists of existing systematic reviews and included studies were reviewed to identify all eligible trials published before 2011.

STUDY SELECTION:

English language trials comparing a protocol of preadmission, preoperative, intraoperative, and postoperative components with usual care in adults undergoing elective colorectal surgery were selected.

INTERVENTION:

The enhanced recovery protocol for colorectal surgery was investigated.

MAIN OUTCOME MEASURES:

Length of stay, perioperative morbidity, mortality, readmission within 30 days, and surgical site infection were the primary outcomes measured.

RESULTS:

Twenty-five trials of open or laparoscopic surgery for cancer or noncancer conditions were included. Enhanced recovery protocols consisted of 4 to 18 components. Few studies fully described the various components. Length of stay (mean reduction, 2.6 days; 95% CI, –3.2 to –2.0) and risk of overall perioperative morbidity (risk ratio, 0.66; 95% CI, 0.54–0.80) were lower in enhanced recovery protocol groups than in usual care groups (moderate-quality evidence). All-cause mortality (rare), readmissions, and surgical site infection rates were similar between protocol groups (low-quality evidence). In predefined subgroup analyses, findings did not vary by surgical approach (open vs laparoscopic) or colorectal condition.

LIMITATIONS:

Protocols varied across studies and little information was provided regarding compliance with, or implementation of, specific protocol components.

CONCLUSIONS:

Enhanced recovery protocols for adults undergoing colorectal surgery improve patient outcomes with no increase in adverse events. Evidence was insufficient regarding which components, or component combinations, are key to improving patient outcomes. PROSPERO registration number: CRD42017067991.
Silicone Migration and Late Hematoma following Silicone Implant Rupture: Case Report and Literature Review
Authors: Dean Riley A. , Glener Adam D. , Thomas Analise B. , Glener Steven R. , Kurtovic Silvia , Erdmann Detlev
Published: August 2018

Distant silicone migration and late postoperative hematoma are rare but serious complications following breast implant rupture. This study describes a case report of both these complications occurring in the same patient. After a review of pertinent literature, the authors found 19 other case reports (20 total patients) with distant silicone migration following breast implant rupture. Median age at the time of presentation was 48 years (range, 21–76), and median time between initial breast augmentation and presentation with silicone migration was 10 years (range, 1–30 years). Sites of migrated silicone included arm/forearm (n = 11), thoracic cavity (n = 4), abdominal wall (n = 3), legs (n = 2), and back (n = 1). A total of 67% of patients had documented trauma to the chest before presentation. Our study highlights the need to consider distant silicone migration in the differential diagnosis when extracapsular implant rupture is suspected.
Achondroplasia With Congenital Onset Glaucoma, and Presumed Axenfeld-Rieger Anomaly
Authors: Nastasi Samantha , Gonzalez Andres , Blake Charles Richard , Beck Allen , Agarwal-Sinha Swati
Published: August 2018

We report the first case to our knowledge of a 1-week-old female infant with familial inherited achondroplasia associated with bilateral congenital onset glaucoma, posterior embryotoxon and iris hypoplasia suggestive of ocular Axenfeld-Rieger anomaly.
Development and Psychometric Testing of the Registered Nurses’ Perceptions of Rewarding Scale
Authors: SEITOVIRTA Jaana , LEHTIMÄKI Aku-Ville , VEHVILÄINEN-JULKUNEN Katri , MITRONEN Lasse , KVIST Tarja
Published: August 2018

Background:

Rewarding is a powerful way to recognize, manage, and retain staff. However, the perceptions of registered nurses (RNs) toward rewarding have not yet been extensively examined in nursing studies. It is important to identify optimal and potentially innovative ways to reward RNs by taking their perceptions into consideration.

Purpose:

The aim of this study was to develop and psychometrically test the Registered Nurses’ Perceptions of Rewarding Scale (RNREWS).

Methods:

A cross-sectional study design was used. The scale was developed in the three phases of item generation, content validity testing, and examination of psychometric properties. Tests of the scale included evaluation of content validity, exploratory factor analysis, parallel analysis, and internal consistency tests using Cronbach’s alpha. Survey participants included 402 RNs working in Finnish healthcare in Autumn 2015.

Results:

The RNREWS was found to have acceptable construct validity and good internal consistency. Exploratory factor analysis indicated that a 66-item scale with a 14-factor structure fits the data best. The final scale includes two subscales. The first is “reward type preferences” with 61 items covering 13 factors, and the second is “significance of rewarding” with five items covering one factor. The two sets of items accounted for 73.1% and 58.5% of the variance in responses and earned Cronbach’s α values of .90 and .80, respectively.

Conclusions:

The RNREWS is a valid and reliable instrument for acquiring knowledge regarding the perspective of RNs on rewarding in the nursing context. The results enhance the understanding of the range of rewards that may be implemented in the nursing profession and may assist human resources managers and administrators to formulate effective reward systems for their RNs to improve the rewarding and retention of nursing professionals. However, cultural equivalence and linguistic differences must be considered if this scale is to be applied in other countries or environments.
Development and Validity Testing of an Assessment Tool for Domestic Elder Abuse
Authors: YI Qinqiuzi , HONDA Junko , HOHASHI Naohiro
Published: August 2018

Background:

The older adult population is increasing in number, and elder abuse is expected to become a more pressing problem. Developing tools to assess the presence and severity of elder abuse is important to both effectively prevent this abuse and provide increased support for families.

Purpose:

This study was intended to test the validity of an Assessment Tool for Domestic Elder Abuse (ATDEA). The items that constitute this tool were derived from a literature review.

Methods:

Two rounds of self-administered questionnaire surveys were conducted with nurses working at home-visit nursing stations. Round 1 was used to evaluate the face validity, and Round 2 was used to test the content using the content validity index (CVI).

Results:

Two hundred forty nurses participated in the two studies. In Round 1, 56 nurses evaluated 38 items derived from a literature review, resulting in the development of a 36-item ATDEA. In Round 2, 184 nurses evaluated the content validity of the 36-item ATDEA. The Item-CVI (I-CVI) scores ranged from .61 to 1. Twenty-eight of the items met or exceeded the I-CVI threshold of .78, whereas the eight items assessing self-neglect did not. The overall Scale-CVI score for the assessment tool was .90, which met the threshold of .90.

Conclusions/Implications for Practice:

The results of validity testing established the preliminary validity of this assessment tool. In addition, as self-neglect is known to damage the well-being of older adults, six of the eight items assessing self-neglect were retained in the ATDEA despite their failure to meet the threshold I-CVI of .78. The remaining two self-neglect items were not included in the ATDEA because of excessively low I-CVI scores (< .70). Thus, the final version of the ATDEA includes 34 items. The authors recommend that nursing professionals use the ATDEA as a checklist to assess the presence of elder abuse and to discern the subtypes and severity of this abuse. When evaluating elder abuse, the higher the degree of severity, the greater the urgency to provide support.
Predictors of Successful Completion of the Master of Physician Assistant Studies in the Netherlands
Authors: van den Brink Geert TWJ , Jans Elisabeth GJM
Published: August 2018

Purpose

The selection of applicants for the Master of Physician Assistant Studies program in the Netherlands is nationally regulated. The minimum criteria are 2 years of experience in health care and a bachelor's degree in nursing or allied health care. However, when students lack the requisite degree, entering a physician assistant (PA) program is possible through an additional assessment process that includes a test of cognitive ability and personality traits. Since 2004, a national registry has tracked all PA students into their employment setting. An evaluation of Master of Physician Assistant graduates who processed through both portals, traditional and alternative, was compared for validation of criteria.

Methods

The success rate of PA students with a bachelor's degree was compared with the success of the cohort that completed the alternative assessment. Descriptive statistics and Pearson's chi square statistics were applied to ascertain differences between the 2 cohorts.

Results

From 2004 to 2014, there were 1241 students enrolled in a PA program in the Netherlands; 184 nurses and nurse anesthetists were enrolled through the alternate pathway. Of the cohort with an assessment, 167 of 184 students (91%) graduated. Of the group with a prerequisite bachelor's degree, 944 students graduated (89%). Differences were considered negligible.

Conclusions

It seems that the nondegree alternative assessment of PA education is a reliable predictor of program completion. Because the nondegree alternative assessment is a national standard screening test, it was decided that there is no need to change the admission procedure for PA applicants.
Implementing vaccine hesitancy screening for targeted education
Authors: Connors John T. , Hodges Eric A. , D'Auria Jennifer , Windham Laura
Published: August 2018

Background and purpose:

Little research has been performed investigating the effect of using a vaccine hesitancy (VH) screening tool to address specific vaccination concerns. The purpose of this study was to determine whether using a VH screening tool in conjunction with provider discussions addressing parental concerns affected the parental intent to vaccinate (ITV).

Methods:

This study used a pretest/posttest design to measure and categorize VH and ITV.

Conclusions:

The total sample size was 89. Differences between previsit and postvisit questionnaires showed mean responses for questions that measured specific VH categories had slight increases in the level of VH. A regression analysis was conducted to predict the postvisit ITV. Questions measuring parental trust in the provider, beliefs on vaccine efficacy, and beliefs about the prevalence of vaccine preventable disease (VPD) in the community predicted 72% of the postvisit ITV responses.

Implications for practice:

The utilization of a VH screening tool used in conjunction with provider education in an educated and mildly VH population did not positively affect the level of VH or the parental ITV. Additional research should investigate the role of parental trust in the provider, beliefs on vaccine efficacy, and the prevalence of VPD in the community affect parental ITV.
Telemedicine simulation in online family nurse practitioner education: Clinical competency and technology integration
Authors: Ainslie Marcy , Bragdon Cheryl
Published: August 2018

Background and purpose:

Assessment of clinical competency in distance education programs presents new challenges and yet is imperative to patient safety and continued success of the profession. Furthermore, employers increasingly expect a skill set in current informational technologies. Clinical competence has been assessed using high stakes, standardized patient simulation in traditional, on-campus educational programs. Telemedicine technology integrated with standardized patient simulations may provide a solution for teaching the essentials of information technology and provide a modality for clinical competency assessment in distance education.

Methods:

Telemedicine was introduced to students via a formative, didactic assignment. This preparation facilitated the use of telemedicine technology integrated with standardized patient simulations to assess clinical competency of online students. In addition, this format required students to apply the fundamentals of informational technologies.

Conclusion:

Combining the modality of telemedicine with high stakes, standardized patient simulation to assess clinical competence is innovative and ensures high standards in distant education while addressing the preparation of students in the use of emerging technologies.

Implications for practice:

Telemedicine integrated with human standardized patient simulation is a promising modality for clinical competency assessment and determination of program progression in distance education. In addition, students become accustomed to the informational technologies encountered in the workplace.
Comparing nurse practitioners/physician assistants and physicians in diagnosing adult abdominal pain in the emergency department
Authors: Hoyt Karen Sue , Ramirez Elda , Topp Robert , Nichols Stephen , Agan Donna
Published: August 2018

Background and purpose:

This retrospective study compared nurse practitioners and physician assistants (NPs/PAs) with physicians on their assignment of Emergency Severity Index level 3 (ESI level 3) acute abdominal pain (AAP) in the emergency department (ED).

Methods:

Data obtained from a large ED group staffing four hospitals yielded 12,440 de-identified, adult patients diagnosed on ED admission with AAP ESI level 3 for descriptive analysis with logistic regression.

Conclusions:

Results revealed that the comparison of ESI level 3 AAP diagnoses was consistent between admission and discharge 95.3% for physicians, 92.9% for NPs/PAs, and 97.1% for NP/PA and physician collaboration (χ2 = 46.01, p < .001). Logistic regression suggested that NP/PA had significantly reduced odds (31%) of consistent admitting/discharge diagnoses, whereas collaboration of NP/PA with physicians had significantly increased odds of consistent diagnosis (41%) compared with physicians alone. Two hospitals with similar distributions of NPs/PAs and physicians exhibited greater odds of consistent diagnoses over hospitals with disproportionate distributions; a secondary finding worth exploring. Consistent AAP ESI level 3 diagnoses by outcomes were admissions (>99%), discharges (94%), and left against medical advice/transferred (98%; χ2 = 102.94, p < .001).

Implications for practice:

The highest percentage of consistent AAP ESI level 3 diagnoses between ED admission and discharge was when NPs/PAs and physicians collaborated.
Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn’s disease
Authors: Molendijk Ilse , van der Meulen – de Jong Andrea E. , Verspaget Hein W. , Veenendaal Roeland A. , Hommes Daniel W. , Bonsing Bert A. , Peeters Koen C.M.J.
Published: August 2018

Background

Local administration of mesenchymal stromal cells (MSCs) into the fistula tract seems to improve patient outcome in perianal fistulas due to Crohn’s disease (CD). In this paper we propose a standardized and validated protocol for the local administration of MSCs for CD perianal fistulas to be able to reliably assess efficacy.

Materials and methods

A working group consisting of gastroenterologists and surgeons with expertise in the treatment of perianal CD developed a consensus perianal fistula treatment protocol for local MSC treatment of perianal fistulizing CD. The treatment protocol was validated during a trial of allogeneic bone marrow-derived MSCs for the treatment of refractory perianal Crohn’s fistulas.

Results

Localization and classification of perianal fistulas with MRI and rectoscopy is of crucial importance prior to surgical intervention with local therapy administration. Examination under anesthesia is necessary to incise and drain abscesses when present. Optimization of medical treatment when active luminal CD is present, is the first step before embarking on surgery and local therapy administration. In addition, strictures preventing the surgeon from adequately performing the surgical procedure have to be endoscopically dilated. Curettage of the fistula tract has an important role as long-standing CD perianal fistulas close poorly without removal of their epithelial lining. To diminish bacterial contamination of the fistula, the internal opening has to be closed. The origin of the fistula is the internal opening, therefore, efficacy of MSCs is presumably the highest when they are injected into the tissue around the internal opening.

Conclusion

In this article, we propose a standardized method of local MSC administration for perianal fistulizing CD. The use of this standardized and validated protocol for the administration of local treatment of CD perianal fistulas will allow reliable comparison of the efficacy of local therapies in future.
Infectious endocarditis in the case of cirrhosis: where do we stand?
Authors: Allaire Manon , Ollivier-Hourmand Isabelle , Garioud Armand , Heng Ratmony , Dao Thong , Cadranel Jean-François D.
Published: August 2018

Bacterial infections are common in the case of cirrhosis and represent a major cause of morbidity and mortality. The most frequent infections are spontaneous bacterial peritonitis, urinary tract infection, and pneumonia, but few data on infectious endocarditis are available. Infectious endocarditis is a rare event, and diagnosis can be made at all stages of Child–Pugh classification. In the case of cirrhosis, the clinical features and bacterial ecology are similar to that of the general population (two males/one female, preferential location on the aortic and mitral valves, history of heart disease, majority of Gram-positive bacteria), but in-hospital mortality is higher. The Child–Pugh score and a history of decompensation have been identified as independent predictive factors for in-hospital mortality and a Child–Pugh score more than C10 was associated with a higher risk of death. Less frequent use of aminoglycosides, rifampin, and cardiac surgery has been described in cirrhotic patients, probably because of potential toxicity. Nevertheless, as they are a cornerstone of therapy, prospective studies on the impact of these therapeutics are warranted to improve outcome in this population of patients.
Primary Ewing Family of Tumor Arising in the Ovary: A Case Report
Authors: Li Yi-Ping , Chang Koping , Chen Tom Wei-Wu , Lee Shu-Ping , Chen Chi-An , Cheng Wen-Fang
Published: August 2018

Ewing sarcoma and peripheral primitive neuroectodermal tumor constitute the Ewing family of tumors (EFT). EFTs primarily arising in the ovary are extremely rare. We report the case of a 22-yr-old nulliparous woman with a primary EFT in the ovary that initially presented as a 3-cm teratoma-like ovarian tumor, with rapid progression to a 15-cm-sized tumor with liver metastasis in 3 mo. The patient underwent suboptimal debulking surgery and salvage chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide. In conclusion, primary EFT in the ovary is extremely rare with highly aggressive behavior and poor outcome for metastatic disease. Demonstration of EWSR1 rearrangement, observed in a variety of soft tissue tumors, is very helpful in the diagnosis of EFT when interpreted on the basis morphology and immunohistochemistry.
The utility and validity of pain intensity rating scales for use in developing countries
Authors: Pathak Anupa , Sharma Saurab , Jensen Mark P.
Published: August 2018

Introduction:

Pain intensity is the domain most often assessed in pain research. Although the Numerical Rating Scale is recommended for use in western countries, the utility and validity of this scale, relative to others, has not been established in non–western developing countries, such as Nepal.

Objectives:

Here, we sought to (1) identify which of 4 commonly used pain scales is most preferred by Nepalese, (2) compare error rates, (3) determine whether preference and error rates are influenced by age or education level, and (4) evaluate construct validity of each scale using factor analysis.

Methods:

Two hundred two adults with musculoskeletal pain from Nepal rated their worst and average pain intensity using all 4 scales and selected their most preferred scale.

Results:

The results indicate that the Faces Pain Scale-Revised is the most preferred scale, followed by a Verbal Rating Scale. The Numerical Rating Scale and Visual Analogue Scale were both least preferred and had higher rates of incorrect responses, especially among the older participants. However, all the scales demonstrated adequate construct validity as measures of pain intensity among those participants who could accurately use all 4 scales.

Conclusion:

The findings indicate that the Faces Pain Scale-Revised should be the first choice for assessing pain intensity in Nepalese adults. Research is needed to determine whether these findings replicate in other non–western and developing countries, to identify the pain intensity measure that would be the best choice for use in cross-cultural pain research.
Clinical Correlation of Cytomegalovirus Infection With CMV-specific CD8+ T-cell Immune Competence Score and Lymphocyte Subsets in Solid Organ Transplant Recipients
Authors: Meesing Atibordee , Abraham Roshini S. , Razonable Raymund R.
Published: August 2018

Background.

Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients.

Methods.

During a 10-year period, selected kidney, heart, lung, pancreas, liver, and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production, and CD107a/b degranulation. Quantitative and functional data were used to assemble T-cell immune competence (TIC) score. CMV infection was diagnosed by polymerase chain reaction in blood and other samples or histopathology.

Results.

Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (interquartile range [IQR], 5.5–18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (hazard risk, 2.84, 95% confidence interval, 1.03–11.81; P = 0.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 days vs 18.8 d; P < 0.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs 27.9%; hazard risk, 2.56; 95% confidence interval, 1.09–5.89; P = 0.03). Patients with CMV infection or disease had lower median absolute lymphocyte count (380 [IQR, 240–540] vs 940 [IQR, 551–1210] cells/mm3; P < 0.0001) and CD4+ T cell count (29 cells/mm3 [IQR, 1.3–116.0] vs 325.5 cells/mm3 [IQR, 151.5–589.8]; P < 0.0001).

Conclusions.

Nonspecific and CMV-specific CD8+ T-cell function correlated with the course of CMV after SOT, and measuring these has the potential to assist in its clinical management.
Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion
Authors: Honap Tanvi P. , Sankaranarayanan Krithivasan , Schnorr Stephanie L. , Ozga Andrew T. , Warinner Christina , Lewis Cecil M.
Published: August 2018

CrAssphage (cross-assembly phage) is a bacteriophage that was first discovered in human gut metagenomic data. CrAssphage belongs to a diverse family of crAss-like bacteriophages thought to infect gut commensal bacteria belonging toBacteroidesspecies. However, not much is known about the biogeography of crAssphage and whether certain strains are associated with specific human populations. In this study, we screened publicly available human gut metagenomic data from 3,341 samples for the presence of crAssphagesensu stricto(NC_024711.1). We found that crAssphage prevalence is low in traditional, hunter-gatherer populations, such as the Hadza from Tanzania and Matses from Peru, as compared to industrialized, urban populations. Statistical comparisons showed no association of crAssphage prevalence with variables such as age, sex, body mass index, and health status of individuals. Phylogenetic analyses show that crAssphage strains reconstructed from the same individual over multiple time-points, cluster together. CrAssphage strains from individuals from the same study population do not always cluster together. Some evidence of clustering is seen at the level of broadly defined geographic regions, however, the relative positions of these clusters within the crAssphage phylogeny are not well-supported. We hypothesize that this lack of strong biogeographic structuring is suggestive of a recent expansion event within crAssphage. Using a Bayesian dating approach, we estimate this expansion has occurred within the past 200 years. Overall, we determine that crAssphage presence is associated with an industrialized lifestyle. The absence of strong biogeographic structuring within global crAssphage strains is likely due to a recent population expansion within this bacteriophage.
Sex overrides mutation in Escherichia coli colonizing the gut
Authors: Frazão N. , Sousa A. , Lässig M. , Gordo I.
Published: August 2018

Bacteria evolve by mutation accumulation in laboratory experiments, but the tempo and mode of evolution in natural environments are largely unknown. Here we show, by experimental evolution of E. coli in the mouse gut, that the ecology of the gut controls bacterial evolution. If a resident E. coli strain is present in the gut, an invading strain evolves by rapid horizontal gene transfer; this mode precedes and outweighs evolution by point mutations. An epidemic infection by two phages drives gene uptake and produces multiple co-existing lineages of phage-carrying (lysogenic) bacteria. A minimal dynamical model explains the temporal pattern of phage epidemics and their complex evolutionary outcome as generic effects of phage-mediated selection. We conclude that phages are an important eco-evolutionary driving force – they accelerate evolution and promote genetic diversity of bacteria.

One Sentence Summary

Bacteriophages drive rapid evolution in the gut.
Functional and structural resilience of the active site loop in the evolution of Plasmodium lactate dehydrogenase
Authors: Wirth Jacob D. , Boucher Jeffrey I. , Jacobowitz Joseph R. , Classen Scott , Theobald Douglas L.
Published: August 2018

The malarial pathogen Plasmodium falciparum (Pf) is a member of the Apicomplexa, which independently evolved a highly specific lactate dehydrogenase (LDH) from an ancestral malate dehydrogenase (MDH) via a five-residue insertion in a key active site loop. PfLDH is widely considered an attractive drug target due to its unique active site. Apicomplexan loop conservation suggests that a particular insertion sequence was required to evolve LDH specificity, and we previously showed (Boucher 2014) that a tryptophan in the insertion, W107f, is essential for activity and specificity. However, the roles of other residues in the loop are currently unknown. Here we show that PfLDH activity is remarkably resilient to radical perturbations of both loop identity and length. Thus, alternative insertions could have evolved LDH specificity as long as they contained a tryptophan in the proper location. PfLDH therefore has high potential to develop resistance to drugs that target its distinctive active site.
Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma
Authors: Gapp K. , van Steenwyk G. , Germain P.L. , Matsushima W. , Rudolph K.L.M. , Manuella F. , Roszkowski M. , Vernaz G. , Ghosh T. , Pelczar P. , Mansuy I.M. , Miska E.A.
Published: August 2018

Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells1,2. Initial evidence suggested that sperm RNA is causally linked2,3to the transmission of symptoms induced by traumatic experiences. Here we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioral despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.
Proliferation of superficial neuromasts during lateral line development in the Round Goby, Neogobius melanostomus
Authors: Dickson J. M. , Janssen J. A.
Published: August 2018

Members of the family Gobiidae have an unusual lateral line morphology in which some of the lateral line canal segments do not develop or enclose. This loss of lateral line canal segments is frequently accompanied by proliferation of superficial neuromasts. Although the proliferation of superficial neuromasts forms intricate patterns that have been used as a taxonomic tool to identify individual gobiid species, there has never been a detailed study that has documented the development of the lateral line system in gobies. The Round Goby, Neogobius melanostomus, is the focus of this study because the absence of the lateral line canal segments below the eye are accompanied by numerous transverse rows of superficial neuromasts. Our results suggest that the origin of some of these superficial neuromast lines could be the result of single presumptive canal neuromasts that have proliferated after canal enclosure is arrested. Many of the intricate patterns of neuromasts observed in gobiids develop from a simplified pattern of neuromast that is very similar among different species of gobies. The proliferation of superficial neuromasts has evolved several times in fish families such as the tetras, gobies, and sculpins, and may provide an adaptive advantage to ‘tune’ the lateral line system for different environments and prey types.

SIGNIFICANCE STATEMENT

Understanding the development of different lateral line morphologies can provide insights into how these morphologies have convergently evolved in many fish taxa. This is the first study to document the progression of the development of the reduced lateral line morphology. This study shows evidence that the developmental origins of orthogonal lines of superficial neuromasts posterior to the eye are not neomorphic lines, but in fact arise from precursor neuromasts that seem to be analogous to presumptive canal neuromasts.
Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium
Authors: Bell Miriam , Bartol Tom , Sejnowski Terrence , Rangamani Padmini
Published: August 2018

Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment in the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multi-compartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources including N-methyl-D-aspartate receptors (NMDAR), voltage sensitive calcium channels (VSCC), and different ion pumps on the plasma membrane. Using this model, we make several important predictions – first, the volume-to-surface area ratio of the spine regulates calcium dynamics, second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion, and finally the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines.
A new model on DNA structure and thermal denaturation
Authors: Liaofu LUO , Guochen YANG
Published: August 2018

A quantum model on DNA structure is proposed. By introducing the self-consistent harmonic potential in the X-Y plane vertical to helix axis (z-direction) and the periodic potential along the z-axis we obtain the wave function for the single nucleotide and the many-nucleotide system. The helix distribution of bases is deduced from the solution of wave function under the self-consistent potential. The variation of DNA structure (polymorphism) is related to the periodicity of the potential in Z-axis, the quantum state occurring in harmonic potential and the interaction between helix strands. As Watson-Crick (W-C) interaction is introduced between double helices, the quasi-particle transformation is utilized to solve the interacting many-body problem for DNA. It is proved that the phase-transition (thermal denaturation) temperature is related to the frequency ω of harmonic potential. Through comparison with experimental data a simple relation (N means number of base pairs and V the W-C coupling) is deduced. For a DNA sequence of 1000 bp ω is predicted about (0.9-1.2)×1017/sec. Such a high frequency is necessary for nucleotides of each strand located on a narrow tube. The large temperature fluctuation experimentally observed during DNA thermal denaturation is interpreted by the collective motion of nucleotides.
The ESCRT-III proteins IST1 and CHMP1B assemble around nucleic acids
Authors: Talledge Nathaniel , McCullough John , Wenzel Dawn , Nguyen Henry C. , Lalonde Matthew S. , Bajorek Monika , Skalicky Jack , Frost Adam , Sundqust Wesley I.
Published: August 2018

ESCRT-III proteins can promote inside-out or outside-in membrane tubulation and fission. In addition, several observations suggest that ESCRT factors may also associate with nucleic acids during development, different stages of the cell cycle, and during retro-transposition of parasitic nucleic acids like LINE1 elements. Two ESCRT-III subunits, IST1 (aka CHMP8) and CHMP1B, can coassemble as an external protein coat around liposomesin vitroand around recycling endosomal tubules in living cells. Here we show that recombinant IST1 and CHMP1B can also copolymerize into double stranded filaments that surround nucleic acids. Electron cryo-microscopy reconstructions of nucleic acid-bound IST1-CHMP1B copolymers revealed that the polynucleotides track along a binding groove formed between filaments of the inner CHMP1B strand. The well-ordered structures also reveal that the C-terminal tails of CHMP1B subunits extrude through the outer IST1 layer to the tube exterior. As a result, the MIT domain binding motifs of both CHMP1B and IST1 are arrayed on the outer surface of the copolymer, where they could bind and recruit MIT domain-containing co-factors, such as the SPASTIN ATPase or the USP8 ubiquitin protease. Our structure raises the possibility that ESCRT-III proteins may form nucleic acid complexes in mammalian cells.
Identification, Genotyping, and Pathogenicity ofTrichosporonspp. Isolated from Giant Pandas
Authors: Ma Xiaoping , Jiang Yaozhang , Wang Chengdong , Gu Yu , Cao Sanjie , Huang Xiaobo , Wen Yiping , Zhao Qin , Wu Rui , Wen Xintian , Yan Qigui , Han Xinfeng , Zuo Zhicai , Deng Junliang , Ren Zhihua , Yu Shumin , Shen Liuhong , Zhong Zhijun , Peng Guangneng , Liu Haifeng , Zhou Ziyao
Published: August 2018

Trichosporonis the dominant genus of epidermal fungi in giant pandas and causes local and deep infections. To provide the information needed for the diagnosis and treatment of trichosporosis in giant pandas, the sequence of ITS, D1/D2, and IGS1 loci in 29 isolates ofTrichosporonspp. which isolated from the body surface of giant pandas were combination to investigate interspecies identification and genotype. Morphological development was examined via slide culture. Additionally, mice were infected by skin inunction, intraperitoneal injection, and subcutaneous injection for evaluation of pathogenicity. The twenty-nine isolates ofTrichosporonspp. were identified as belonging to 11 species, andTrichosporon jiroveciiandT. asteroideswere the commonest species. Four strains ofT. laibachiiand one strain ofT. moniliiformewere found to be of novel genotypes, andT. jiroveciiwas identified to be genotype 1.T. asteroideshad the same genotype which involved in disseminated trichosporosis. The morphological development processes of theTrichosporonspp. were clearly different, especially in the processes of single-spore development. Pathogenicity studies showed that 7 species damaged the liver and skin in mice, and their pathogenicity was stronger than other 4 species.T. asteroideshad the strongest pathogenicity and might provoke invasive infection. The pathological characteristics of liver and skin infections caused by differentTrichosporonspp. were similar. So it is necessary to identify the species ofTrichosporonon the surface of giant panda. Combination of ITS, D1/D2, and IGS1 loci analysis, and morphological development process can effectively identify the genotype ofTrichosporonspp.
AICM: A Genuine Framework for Correcting Inconsistency Between Large Pharmacogenomics Datasets
Authors: Tom Hu Zhiyue , Ye Yuting , Newbury Patrick A. , Huang Haiyan , Chen Bin
Published: August 2018

The inconsistency of open pharmacogenomics datasets produced by different studies limits the usage of pharmacogenomics in biomarker discovery. Investigation of multiple pharmacogenomics datasets confirmed that the pairwise sensitivity data correlation between drugs, or rows, across different studies (drug-wise) is relatively low, while the pairwise sensitivity data correlation between cell-lines, or columns, across different studies (cell-wise) is considerably strong. This common interesting observation across multiple pharmacogenomics datasets suggests the existence of subtle consistency among the different studies (i.e., strong cell-wise correlation). However, significant noises are also shown (i.e., weak drug-wise correlation) and have prevented researchers from comfortably using the data directly. Motivated by this observation, we propose a novel framework for addressing the inconsistency
between large-scale pharmacogenomics data sets. Our method can significantly boost the drug-wise correlation and can be easily applied to re-summarized and normalized datasets proposed by others. We also investigate our algorithm based on many different criteria to demonstrate that the corrected datasets are not only consistent, but also biologically meaningful. Eventually, we propose to extend our main algorithm into a framework, so that in the future when more data-sets become publicly available, our framework can hopefully offer a “ground-truth” guidance for references.
Ena/VASP processive elongation is modulated by avidity on actin filaments bundled by the filopodia crosslinker fascin
Authors: Harker Alyssa J. , Katkar Harshwardhan H. , Bidone Tamara C. , Aydin Fikret , Voth Gregory A. , Applewhite Derek A. , Kovar David R.
Published: August 2018

Ena/VASP are tetrameric assembly factors that bind F-actin barbed ends continuously while increasing their elongation rate within dynamic bundled networks such as filopodia. We used single-molecule TIRFM and developed a kinetic model to dissect Ena/VASP’s processive mechanism on bundled filaments. Notably, Ena/VASP’s processive run length increases with the number of both bundled filaments and Ena arms, revealing avidity facilitates enhanced processivity. Moreover, Ena tetramers form more filopodia than mutant dimer and trimers in Drosophila culture cells. Finally, enhanced processivity on trailing barbed ends of bundled filaments is an evolutionarily conserved property of Ena/VASP homologs and is specific to fascin-bundled filaments. These results demonstrate that Ena tetramers are tailored for enhanced processivity on fascin bundles and avidity of multiple arms associating with multiple filaments is critical for this process. Furthermore, we discovered a novel regulatory mechanism whereby bundle size and bundling protein specificity control activities of a processive assembly factor.
A Key For Hypoxia Genetic Adaptation In Alpaca Could Be A HIF1A Truncated bHLH Protein Domain
Authors: Daniel Moraga M , Moraga C Fernando A. , Figueroa Felipe
Published: August 2018

Animals exposed to hypoxia, triggers a physiological response via Hypoxia Inducible Factors (HIF1). In this study, we have evidenced the existence of genetic events that caused the loss of most of the bHLH domain in HIF1A proteins borne by Alpaca and other members of the Cetartiodactyla superorder. In these truncate domains, some stop codons are found at identical nucleotide positions in both, Artiodactyls and Cetaceans, indicating that mutations originating the truncated domains occurs before their divergence about 55 million years ago. The relevance of this findings for adaptation of Alpacas to hypoxia of high altitude conditions are discussed.
General Budget Support in Tanzania
Authors: Furukawa Mitsuaki , Takahata Junichiro
Published: August 2018

Purpose

The purpose of this paper is to analyze late disbursements for service delivery by focusing on donors’ General Budget Support disbursement to Tanzania and on the intergovernmental money flows in Tanzania.

Design/methodology/approach

The authors examined empirical analysis using statistics of intergovernmental transfers in Tanzania.

Findings

This paper shows that such center-local transfers are significantly correlated with the timing of local government expenditures in general and health expenditures in particular. It also shows that development expenditures are more affected than recurrent expenditures by delays in the transfer.

Practical implications

In order to improve service delivery on the ground, the transfers from donors to the central government and from the central government to local governments need to be timely.

Originality/value

The authors examined empirical analysis using statistics of intergovernmental transfers in Tanzania so as to see whether timing of transfers matters or not, which has not been considered thus far.
Short food supply chain between micro/small farms and restaurants
Authors: Paciarotti Claudia , Torregiani Francesco
Published: August 2018

Purpose

The purpose of this paper is to explore the strength and weakness connected to the implementation of a local food logistics services, designed to facilitate and enable the use of local food among restaurants.

Design/methodology/approach

A total of 60 restaurateurs located in a small Italian city and 100 owners of micro and small-sized farms, located within a 30 km radius from the city, have been interviewed. The collected data have been analysed through descriptive analysis and Kruskal-Wallis and Mann-Whitney U tests for differences between gender, production type and business size.

Findings

The results agree with existing literature: poor communication and an unstructured logistics limit the interaction among actors. However, significant for the purpose, the data show that producers are interested in expanding their market and restaurateurs are interested in a broader supply of local products, and they both open to a logistics service that improves the supply of local food.

Research limitations/implications

The following exploratory study is based on a sample of farmers and restaurants in a specific area so the results could not be generalised in a national/international context.

Practical implications

The logistics service objective is the promotion of a sustainable territory development in support of the social economy values.

Originality/value

The study investigates this issue focussing on a practical solution of local food distribution system among restaurants. The logistics service tends to solve the logistics criticalities maintaining the principles of the short food supply chain.