bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissipation of contractile forces: the missing piece in cell mechanics
Authors: Kurzawa Laetitia , Vianay Benoit , Senger Fabrice , Vignaud Timothée , Blanchoin Laurent , Théry Manuel
Published: July 2017

Mechanical forces are key regulators of cell and tissue physiology. The basic molecular mechanism of fiber contraction by the sliding of actin filament upon myosin leading to conformational change has been known for decades. The regulation of force generation at the level of the cell, however, is still far from elucidated. Indeed, the magnitude of cell traction forces on the underlying extracellular matrix in culture is almost impossible to predict or experimentally control. The considerable variability in measurements of cell-traction forces indicates that they may not be the optimal readout to properly characterize cell contractile state and that a significant part of the contractile energy is not transferred to cell anchorage but instead is involved in actin network dynamics. Here we discuss the experimental, numerical, and biological parameters that may be responsible for the variability in traction force production. We argue that limiting these sources of variability and investigating the dissipation of mechanical work that occurs with structural rearrangements and the disengagement of force transmission is key for further understanding of cell mechanics.
Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
Authors: Frost Hannah R , Laho Delphine , Sanderson-Smith Martina L , Licciardi Paul , Donath Susan , Curtis Nigel , Kado Joseph , Dale James B , Steer Andrew C , Smeesters Pierre R
Published: July 2017

Background

Group AStreptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 differentemm types, is immunogenic and elicits protective antibodies. A major obstacle for vaccine development has been the traditional understanding that immunity following infection is restricted to a singleemm type. However, recent evidence has led to the hypothesis of immune cross-reactivity betweenemm types.

Methods

We investigated the human serological response to GAS impetigo in Fijian schoolchildren, focusing on 3 majoremm clusters (E4, E6, and D4). Pre- and postinfection sera were assayed by enzyme-linked immunosorbent assay with N-terminal M peptides and bactericidal assays using the infecting-type strain,emm cluster–related strains, and nonrelated strains.

Results

Twenty of the 53 paired sera demonstrated a ≥4-fold increase in antibody titer against the infecting type. When tested against all cluster-related M peptides, we found that 9 of 17 (53%) paired sera had a ≥4-fold increase in antibody titer to cluster-related strains as well. When grouped by cluster, the mean change to cluster-relatedemm types in E4 and E6 was >4-fold (5.9-fold and 19.5-fold, respectively) but for D4 was 3.8-fold. The 17 paired sera were tested in bactericidal assays against selected cluster-related and nonrelated strains. While the responses were highly variable, numerous instances of cross-reactive killing were observed.

Conclusions

These data demonstrate that M type–specific and cross-reactive immune responses occur following skin infection. The cross-reactive immune responses frequently align withemm clusters, raising new opportunities to design multivalent vaccines with broad coverage.
An Upper Limit on the Functional Fraction of the Human Genome
Authors: Graur Dan
Published: July 2017

For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 15%.
Similar oyster reproduction across estuarine regions differing in carbonate chemistry
Authors: Ruesink J L , Sarich A , Trimble A C
Published: July 2017

In laboratory studies, shellfish larvae often respond negatively to augmented [CO2], but no prior tests have related wild bivalve larval performance and carbonate chemistry spatiotemporally. The geography of Willapa Bay (Washington, USA) naturally generates two distinct regions of carbonate chemistry where non-native Pacific oysters (Crassostrea gigas) dominate the intertidal fauna and successfully reproduce. On the river-influenced east side, pCO2 is higher and alkalinity lower, which both contribute to reduced aragonite saturation state (Ωaragonite 1.3–1.5) relative to the west side receiving low watershed inputs (Ωaragonite 1.8–1.9). pHsws is also >0.1 lower on the east vs. west sides. Despite this difference in field conditions, no biological signal related to carbonate chemistry was apparent in oyster reproduction based on coupled chemical–biological comparisons over three summers. Instead, survival was equal between the two sides of the bay, and settlement was equal or higher on the low-Ωaragonite, low-pH east side. In a temporal comparison of four larval cohorts, settlement differed by two orders of magnitude and increased with water temperature. These field data on oyster reproduction illustrate that population-level effects may not emerge in higher mean [CO2] conditions, with possible decoupling due to local adaptation, spatio-temporal heterogeneity, or higher sensitivity to other axes of environmental variability such as temperature.
Are participants concerned about privacy and security when using short message service to report product adherence in a rectal microbicide trial?
Authors: Giguere Rebecca , Brown III William , Balán Ivan C , Dolezal Curtis , Ho Titcha , Sheinfil Alan , Ibitoye Mobolaji , Lama Javier R , McGowan Ian , Cranston Ross D , Carballo-Diéguez Alex
Published: July 2017

Objective

During a Phase 2 rectal microbicide trial, men who have sex with men and transgender women (n = 187) in 4 countries (Peru, South Africa, Thailand, United States) reported product use daily via short message service (SMS). To prevent disclosure of study participation, the SMS system program included privacy and security features. We evaluated participants’ perceptions of privacy while using the system and acceptability of privacy/security features.

Materials and Methods

To protect privacy, the SMS system: (1) confirmed participant availability before sending the study questions, (2) required a password, and (3) did not reveal product name or study participation. To ensure security, the system reminded participants to lock phone/delete messages. A computer-assisted self-interview (CASI), administered at the final visit, measured burden of privacy and security features and SMS privacy concerns. A subsample of 33 participants underwent an in-depth interview (IDI).

Results

Based on CASI, 85% had no privacy concerns; only 5% were very concerned. Most were not bothered by the need for a password (73%) or instructions to delete messages (82%). Based on IDI, reasons for low privacy concerns included sending SMS in private or feeling that texting would not draw attention. A few IDI participants found the password unnecessary and more than half did not delete messages.

Discussion

Most participants were not concerned that the SMS system would compromise their confidentiality. SMS privacy and security features were effective and not burdensome.

Conclusion

Short ID-related passwords, ambiguous language, and reminders to implement privacy and security-enhancing behaviors are recommended for SMS systems.
Quality of life of irradiated brain tumor survivors treated with donepezil or placebo: Results of the WFU CCOP research base protocol 91105
Authors: Naughton Michelle J , Case L Douglas , Peiffer Ann , Chan Michael , Stieber Volker , Moore Dennis , Falchuk Steven , Piephoff James , Edenfield William , Giguere Jeffrey , Loghin Monica , Shaw Edward G , Rapp Stephen R
Published: July 2017

Background

The health-related quality of life (HRQL) and fatigue of brain cancer survivors treated with donepezil or placebo for cognitive symptoms after radiation therapy were examined.

Methods

One hundred ninety-eight patients who completed >30 Gy fractionated whole or partial brain irradiation at least 6 months prior to enrollment were randomized to either placebo or donepezil (5 mg for 6 weeks followed by 10 mg for 18 weeks) in a phase 3 trial. A neurocognitive battery, the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, was administered at baseline, 12 weeks, and 24 weeks.

Results

At 12 weeks, donepezil resulted in improvements in only emotional functioning (P = .04), with no significant effects at week 24. Associations by level of baseline cognitive symptoms (above or below the median score of the baseline FACT-Br “additional concerns/brain” subscale), indicated that participants with more baseline symptoms who received donepezil versus placebo, showed improvements in social (P = .02) and emotional well-being (P = .038), other concerns/brain (P = .003) and the FACT-Br total score (P = .004) at 12 weeks, but not 24 weeks. However, participants with fewer baseline symptoms randomized to donepezil versus placebo reported lower functional well-being at both 12 (P = .015) and 24 weeks (P = .009), and greater fatigue (P = .02) at 24 weeks.

Conclusions

The positive impact of donepezil on HRQL was greater in survivors reporting more baseline cognitive symptoms. Donepezil had significantly worse effects on fatigue and functional well-being among participants with fewer baseline symptoms. Future interventions with donepezil should target participants with more baseline cognitive complaints to achieve greater therapeutic impact and lessen potential side effects of treatment.
A Novel 4-Rod Technique Offers Potential to Reduce Rod Breakage and Pseudarthrosis in Pedicle Subtraction Osteotomies for Adult Spinal Deformity Correction
Authors: Gupta Sachin , Eksi Murat Sakir , Ames Christopher P , Deviren Vedat , Durbin-Johnson Blythe , Smith Justin S , Gupta Munish C
Published: July 2017

BACKGROUND

Pedicle subtraction osteotomy (PSO) can be used to treat rigid sagittal plane deformities. Nonunions and rod breakages are known complications of PSO.

OBJECTIVE

To assess outcomes of 2 methods of posterior instrumentation for PSO, traditional 2 rods vs a novel 4-rod technique in which 2 additional rods span only the osteotomy level.

METHODS

This study was a retrospective, radiographic review of consecutive PSOs performed at 2 centers. The primary difference in technique between the centers was the use of 4 rods including 2 independent rods attached only to the vertebral levels immediately adjacent to the PSO (group 1, n = 29 patients) vs the traditional 2-rod technique (group 2, n = 20 patients).

RESULTS

Demographics and preoperative to postoperative radiographic measurements were similar between the study groups, including the PSO wedge resection angle (P = .56). The rod breakage rate was 25% with 2 rods and 0% with 4 rods (P = .008), and the pseudarthrosis rate with 2 rods was 25% and with 4 rods was 3.4% (P = .035). The patient with pseudarthrosis from group 1 had an infection and developed pseudarthrosis only after instrumentation removal. Rates of other complications did not differ significantly between the study groups.

CONCLUSION

This study provides a comparison between 2 techniques for rod placement across a PSO and suggests that the described novel 4-rod technique may help to reduce the rates of pseudarthrosis and rod failure. It will be important to confirm these findings in a prospectively designed study with multiple institutions in order to better control for potentially confounding factors.
Clans, Guilds, and Markets: Apprenticeship Institutions and Growth in the Preindustrial Economy*
Authors: de la Croix David , Doepke Matthias , Mokyr Joel
Published: July 2017

In the centuries leading up to the Industrial Revolution, Western Europe gradually pulled ahead of other world regions in terms of technological creativity, population growth, and income per capita. We argue that superior institutions for the creation and dissemination of productive knowledge help explain the European advantage. We build a model of technological progress in a preindustrial economy that emphasizes the person-to-person transmission of tacit knowledge. The young learn as apprentices from the old. Institutions such as the family, the clan, the guild, and the market organize who learns from whom. We argue that medieval European institutions such as guilds, and specific features such as journeymanship, can explain the rise of Europe relative to regions that relied on the transmission of knowledge within closed kinship systems (extended families or clans).
Recombination of Virulence Genes in Divergent Acidovorax avenae Strains That Infect a Common Host
Authors: Zeng Quan , Wang Jie , Bertels Frederic , Giordano Paul R. , Chilvers Martin I. , Huntley Regan B. , Vargas Joseph M. , Sundin George W. , Jacobs Janette L. , Yang Ching-Hong
Published: July 2017

Bacterial etiolation and decline (BED), caused by Acidovorax avenae, is an emerging disease of creeping bentgrass on golf courses in the United States. We performed the first comprehensive analysis of A. avenae on a nationwide collection of turfgrass- and maize-pathogenic A. avenae. Surprisingly, our results reveal that the turfgrass-pathogenic A. avenae in North America are not only highly divergent but also belong to two distinct phylogroups. Both phylogroups specifically infect turfgrass but are more closely related to maize pathogens than to each other. This suggests that, although the disease is only recently reported, it has likely been infecting turfgrass for a long time. To identify a genetic basis for the host specificity, we searched for genes closely related among turfgrass strains but distantly related to their homologs from maize strains. We found a cluster of 11 such genes generated by three ancient recombination events within the type III secretion system (T3SS) pathogenicity island. Ever since the recombination, the cluster has been conserved by strong purifying selection, hinting at its selective importance. Together our analyses suggest that BED is an ancient disease that may owe its host specificity to a highly conserved cluster of 11 T3SS genes.
Phenotype and Cellular Response of Wheat Lines Carrying Cre Genes to Heterodera avenae Pathotype Ha91
Authors: Cui Jiangkuan , Peng Huan , Huang Wenkun , Liu Shiming , Wu Duqing , Kong Lingan , He Wenting , Peng Deliang
Published: July 2017

The cereal cyst nematode (CCN, Heterodera avenae), a major limiting factor for wheat production worldwide, is widespread in most wheat-growing regions in China. Accordingly, screening and characterization of resistant (R) wheat sources against H. avenae are very important. In this study, we screened 51 wheat lines, collected from the International Wheat and Maize Improvement Center (CIMMYT), carrying various Cre genes (Cre1, Cre2, Cre3, Cre5, Cre7, Cre8, CreR, and Pt). From that screen, we identified one immune (M) cultivar (with no adult females produced) and five resistant cultivars (with fewer than five females) to H. avenae pathotype Ha91. The Cre3 gene conferred the most effective resistance against H. avenae pathotype Ha91 in both field and greenhouse assays. Conversely, the Cre1 and CreR genes conferred the poorest effective resistance. Using Pluronic F-127 gel and a staining assay, juvenile nematodes invading wheat roots were observed, and nematode development was analyzed. Compared with R and M roots, those of the susceptible (S) wheat cultivar Wenmai19 were more attractive to H. avenae second-stage juveniles (J2s). We observed the retardation of nematode development in R cultivars and tiny white female cysts protruding from the R cultivar VP1620. Nematodes in M roots either disintegrated or remained J2s or third-stage juveniles (J3s) and failed to complete their life cycle. Molting was also suppressed or delayed in R and M genotypes. For both S and R cultivars, syncytia were characterized by cell wall perforations and dense cytoplasm in hypertrophied syncytium component cells. Syncytial size increased gradually with nematode development in S cultivars. Moreover, an incompatibility reaction occurred in M wheat roots: the syncytium was disorganized, exhibiting disintegration and condensed nuclei. These sources of genetic resistance against CCN can potentially be planted in severely infested fields to reduce economic loss or can be used for introgression in breeding.
Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution’s Main Source of Income Influence the Results? An Analysis of 21,103 Patients*
Authors: Machado Flavia R. , Ferreira Elaine M. , Sousa Juliana Lubarino , Silva Carla , Schippers Pierre , Pereira Adriano , Cardoso Ilusca M. , Salomão Reinaldo , Japiassu Andre , Akamine Nelson , Mazza Bruno F. , Assunção Murillo S. C. , Fernandes Haggeas S. , Bossa Aline , Monteiro Mariana B. , Caixeita Noemi , Azevedo Luciano C. P. , Silva Eliezer
Published: July 2017

Objective:

We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions’ main source of income (public or private).

Design:

Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014.

Settings:

Brazilian public and private institutions.

Patients:

Patients with sepsis admitted in the participant institutions.

Interventions:

The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle.

Measurements and Main Results:

We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p< 0.0001) and from 7.4% to 15.7% in the public institutions (p< 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32–0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods.

Conclusion:

This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.
Loop Ileostomy Closure as an Overnight Procedure: Institutional Comparison With the National Surgical Quality Improvement Project Data Set
Authors: Berger Nicholas G. , Chou Raymond , Toy Elliot S. , Ludwig Kirk A. , Ridolfi Timothy J. , Peterson Carrie Y.
Published: July 2017

BACKGROUND:

Enhanced recovery pathways have decreased length of stay after colorectal surgery. Loop ileostomy closure remains a challenge, because patients experience high readmission rates, and validation of enhanced recovery pathways has not been demonstrated. This study examined a protocol whereby patients were discharged on the first postoperative day and instructed to advance their diet at home with close telephone follow-up.

OBJECTIVE:

The hypothesis was that patients can be safely discharged the day after loop closure, leading to shorter length of stay without increased rates of readmission or complications.

DESIGN:

Patients undergoing loop ileostomy closure were queried from the American College of Surgeons National Surgical Quality Improvement Project and compared with a single institution (2012–2015). Length of stay, 30-day readmission, and 30-day morbidity data were analyzed.

SETTINGS:

The study was conducted at a tertiary university department.

PATIENTS:

The study includes 1602 patients: 1517 from the National Surgical Quality Improvement Project database and 85 from a single institution.

MAIN OUTCOME MEASURES:

Length of stay and readmission rates were measured.

RESULTS:

Median length of stay was less at the single institution compared with control (2 vs 4 d; p < 0.001). Thirty-day readmission (15.3% vs 10.4%; p = 0.15) and overall 30-day complications (15.3% vs 16.7%; p = 0.73) were similar between cohorts. Estimated adjusted length of stay was less in the single institution (2.93 vs 5.58 d; p < 0.0001). There was no difference in the odds of readmission (p = 0.22).

LIMITATIONS:

The main limitations of this study include its retrospective nature and limitations of the National Surgical Quality Improvement Program database.

CONCLUSIONS:

Next-day discharge with protocoled diet advancement and telephone follow-up is acceptable after loop ileostomy closure. Patients can benefit from decreased length of stay without an increase in readmission or complications. This has the potential to change the practice of postoperative management of loop ileostomy closure, as well as to decrease cost. See Video Abstract at http://links.lww.com/DCR/A310.
Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer
Authors: Jäger Tarkan , Neureiter Daniel , Urbas Romana , Klieser Eckhard , Hitzl Wolfgang , Emmanuel Klaus , Dinnewitzer Adam
Published: July 2017

BACKGROUND:

Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma.

OBJECTIVE:

This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer.

DESIGN:

This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database.

SETTINGS:

This study was performed at a single tertiary referral center.

PATIENTS:

A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included.

MAIN OUTCOMES MEASURES:

The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates.

RESULTS:

Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.

After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04).

LIMITATIONS:

This was a retrospective study.

CONCLUSIONS:

Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.
Lamotrigine Drug Interactions in Combination Therapy and the Influence of Therapeutic Drug Monitoring on Clinical Outcomes of Adult Patients
Authors: Grundmann Milan , Koristkova Blanka , Brozmanova Hana , Kacirova Ivana
Published: July 2017

Background:

The aim was to study the impact of therapeutic drug monitoring (TDM) on patients on lamotrigine (LTG) therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations.

Methods:

During the period of 2001–2014, 3118 predose samples were taken from 1137 patients >15 years of age as part of their routine TDM. Drug interactions were evaluated using calculation of LTG clearance (CL).

Results:

Valproic acid (VPA) decreased LTG CL by 66% in bitherapy, and by 35% and 31% in triple therapy with carbamazepine (CBZ) and phenytoin (PHT), respectively. CBZ and PHT increased LTG CL by 52% and 96% in respective bitherapies but by 88% in triple therapy. Clonazepam, levetiracetam, and topiramate had no effect. The LTG therapeutic range (TR) was exceeded in 1% of cases in monotherapy, and in 4%–5% of cases in combination therapy. Only 54% of results were within the TR during 2001–2005, whereas 60%–62% were within the TR during 2006–2014. Adverse drug reactions (ADRs) were reported in 88 cases and occurred more frequently during TR during 2001–2005. Higher number of supratherapeutic levels in combination therapy led to a 3-fold higher incidence of ADR and poorer seizure control, as seizures occurred more often monthly (2.5%) or a few per year (41%) and fewer patients were seizure free (18%). Seizures occurred more often daily and monthly during the first period and in patients with 3 or 4 drugs in combination.

Conclusions:

A significantly higher number of supratherapeutic levels were found in combinations with VPA, despite lower doses of LTG. Hepatic enzyme inducers, such as CBZ and PHT only partially compensated for the inhibitory effect of VPA. Decrease of both the frequency of seizures and the incidence of ADRs after TDM implementation suggests that TDM may have given clinicians the opportunity to achieve more optimal patient treatment.
Brain imaging of pain sensitization in patients with knee osteoarthritis
Authors: Pujol Jesus , Martínez-Vilavella Gerard , Llorente-Onaindia Jone , Harrison Ben J. , López-Solà Marina , López-Ruiz Marina , Blanco-Hinojo Laura , Benito Pere , Deus Joan , Monfort Jordi
Published: July 2017

A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.
Increasing access to hearing rehabilitation for older adults
Authors: Nieman Carrie L. , Lin Frank R.
Published: July 2017

Purpose of review

To provide an update on the recent research and policy developments affecting the current and future care of the 23 million older Americans with untreated hearing loss.

Recent findings

Increasing evidence supports the association of age-related hearing loss with significant negative outcomes that affect the ability of older adults to age well. Despite an evolving understanding of the role hearing loss plays in the well being and vitality of older adults, the vast majority of older adults go untreated and hearing health care disparities exist. Recent work to understand the multitude of factors involved in hearing health care decisions, coupled with innovative approaches and technology to deliver hearing care, aim to provide more older adults with equal access to the tools needed to age well. Most importantly, significant national efforts and policy proposals substantiate these efforts and will be reviewed.

Age-related hearing loss is a critical public health issue that affects almost all older adults. Through the application of novel approaches and perspectives, the delivery of hearing health care for older adults is evolving to provide more affordable and accessible care. Accompanying policy efforts provide the necessary support needed to increase access to care significantly.
Improving Rapid Response Recognition
Authors: Kindl Heather , Martin Angela , Spade Kathy , Williams Felecia , Clarke Kim
Published: July 2017

New graduate nurses (NGNs) are not fully prepared to recognize and react to rapidly declining patient conditions. Academic curricula typically do not target education related to rapid response events. A study was conducted to evaluate if a collaborative simulation between senior nursing students and NGNs would develop and improve the knowledge and skills needed to recognize and react to a patient who is rapidly deteriorating. Outcomes showed that participants made gains in the areas of competence, prioritization, and communication. This model can be used by other nurses in professional development to increase NGN competence, confidence, and safety.
Using the Magnet® Model to Develop a State of Nursing Report
Authors: Auditore Anthony , Karsten Kathleen , Rolston Elizabeth J. , McMillan-Coddington Deborah
Published: July 2017

Magnet® designation is a prestigious recognition given to a hospital for two reasons: excellence in nursing care and outstanding patient outcomes. Professional development specialists are in a primary position to mentor direct care nursing staff to take ownership, accountability, and responsibility for their practice through the cultivation of a report demonstrating Magnet® engagement and readiness. A State of Nursing report was developed, employing the Magnet® components to fortify the commitment to nursing excellence.
Application Strategies and Tips for Using the Nursing Professional Development Practice Model
Authors: Cobb Susan C.
Published: July 2017

In the past year since the 3rd edition of the Nursing Professional Development: Scope and Standards of Practice was released, many Nursing Professional Development departments across the nation have incorporated this foundational document into their practice. In this column, we continue to describe the activities of our colleagues to integrate the scope and standards into practice.
Peer Education Versus Computer-Based Education
Authors: Gonzalez Roxana , O’Brien-Barry Patricia , Ancheta Reginaldo , Razal Rennuel , Clyne Mary Ellen
Published: July 2017

A quasiexperimental study was conducted to demonstrate which teaching modality, peer education or computer-based education, improves the utilization of the library electronic databases and thereby evidence-based knowledge at the point of care. No significant differences were found between the teaching modalities. However, the study identified the need to explore professional development teaching modalities outside the traditional classroom to support an evidence-based practice healthcare environment.
Functional Balance Deterioration on Daily Activities in Patients With Migraine
Authors: Carvalho Gabriela F. , Florencio Lidiane L. , Pinheiro Carina F. , Dach Fabiola , Bigal Marcelo E. , Bevilaqua-Grossi Débora
Published: July 2017

Objective

This study aimed to assess functional activities in different subgroups of patients with migraine.

Design

One-hundred forty subjects were uniformly divided into the following four groups: headache-free controls, migraine with aura, without aura, and chronic migraine. Subjects performed the tests walk across, tandem walk, sit to stand, and step up and over at the Balance Master system (Neurocom).

Results

All migraine groups had slower velocity and shorter step length at the walk across test (P < 0.0009). The step width was wider in migraine with aura and chronic migraine groups (P < 0.03). At the tandem walk test, patients with migraine exhibited slower velocity and wider step width (P < 0.03). All migraine groups were different than controls at weight transfer and rising index of the sit-to-stand test (P < 0.002). At the step-up-and-over test, there were differences in all outcomes of both legs between headache-free controls versus migraine groups (P < 0.02) and at one outcome between without aura versus migraine with aura (P < 0.01). Moderate to high effect sizes were found for all tests on at least two outcomes assessed, mostly between controls compared with migraine groups.

Conclusions

Migraine is related to changes in the performance of functional tasks, suggesting early motor control deterioration. Proper balance assessment and rehabilitation strategies should be considered for these patients.
Effect of Cervical Siphon of External and Internal Carotid Arteries
Authors: Singh Rajani , Tubbs Richard Shane
Published: July 2017

Variant courses, configuration, and branching pattern of the external and internal carotid arteries, especially when curved in S-shape, are important for hemodynamic changes and clinical implications. Therefore, the aim of the study is to report abnormal cervical siphons observed in external and internal carotid arteries to explore clinical significance by review of literature and hemodynamic changes theoretically.

The right common carotid artery bifurcated into external and internal carotid arteries at the level of the upper border of thyroid cartilage in a 70-year-old female cadaver. After bifurcation, the external carotid artery underwent severe tortuosity coursing through 5 bends at points A, B, C, D, and E from its origin to termination and 2 bends at A’ and B’ in internal carotid artery in the cervical region. The angles between inflow and out flow of the blood at the bends were measured and the change in velocity at each bend was computed for both arteries. Hemodynamic changes were calculated, compared and relevant clinical complications were theoretically correlated.

The angles of 20°, 30°, 51°, 52°, 60°, and 28°, 48° were formed by 5 bends of external and 2 bends of internal carotid arteries, respectively. The curved courses of these arteries caused reduction in velocity/stasis, turbulence, and low shear stress. Such kinks might cause stroke, ischemia and mistaken for tumors and abscess in imagery leading to or otherwise producing iatrogenic repercussions. This study will be useful for anatomists, clinicians, and radiologists.
Respiratory problems in low-resource settings
Authors: Leng Mhoira E.F. , Daniel Sunitha , Munday Daniel
Published: July 2017

Purpose of review

Chronic breathlessness is common in patients with advanced illness who require palliative care. Achieving good symptom control can be challenging. More people with advanced illness live in low and middle income than in high-income countries, but they are much less likely to receive palliative care. Most of the emerging evidence for the palliative management of chronic breathlessness is from high-income countries. This review explores the context of chronic breathlessness in low-income settings, how evidence for control of chronic breathlessness might relate to these settings and where further work should be focused.

Recent findings

Systems for control of noncommunicable diseases (NCDs) in these low-income contexts are poorly developed and health services are often overwhelmed with high levels both of NCD and communicable disease. Multidisciplinary and holistic approaches to disease management are often lacking in these settings. Developing an integrated primary care approach to NCD management is increasingly recognized as a key strategy and this should include palliative care. Most evidence-based approaches to the control of chronic breathlessness could be adapted for use in these contexts

Hand held fans, breathing techniques, graded exercise and use of low-dose morphine can all be used in low-income settings particularly in the context of holistic care. Research is needed into the most effective ways of implementing such interventions and palliative care needs to be promoted as a fundamental aspect of NCD management.
Can High-Dose Levetiracetam Be Safe? A Case Report of Prolonged Accidental High-Dose Levetiracetam Administration and Review of the Literature
Authors: Kartal Ayse
Published: July 2017

Levetiracetam is an antiepileptic drug that has been used both as adjunctive therapy and monotherapy in pediatric patients with epilepsy. We report a patient with cerebral palsy and epilepsy who took 200 mg/kg per day of levetiracetam for 55 days with no apparent adverse effects. Four other cases of accidental overdose were found in the literature; none of these was associated with any apparent adverse effects. These findings suggest that, in at least some cases, levetiracetam doses much higher than the recommended maximum of 60 mg/kg per day can be administered without apparent adverse effects.
The Insula in Temporal Plus Epilepsy
Authors: Barba Carmen , Minotti Lorella , Job Anne-Sophie , Kahane Philippe
Published: July 2017

Temporal lobe epilepsy (TLE) surgery is the most common type of surgical treatment offered to patients with drug-resistant focal seizures. However, the proportion of patients experiencing long-term freedom from seizures after TLE surgery remains suboptimal. Temporal plus epilepsy, which is characterized by a primary temporal epileptogenic zone extending to neighboring regions, has been demonstrated to be a major predictor of TLE surgery failures. In the context of the temporoperisylvian epilepsies, i.e., the most common type of temporal plus epilepsy, a possible role of the insula has often been hypothesized. As this area is buried deep within the lateral sulcus, the use of invasive recordings is often required. Identifying patients with temporal plus seizures is a relevant issue, as they appear to have a worse postsurgical seizure outcome compared with patients with “pure” temporal lobe seizures. Owing to these prognostic implications, it becomes important to identify, among patients suffering from “atypical” nonlesional TLEs, those who should undergo invasive investigations, in particular to explore the insula. In fact, only a primary involvement of the insula in the epileptogenic network may require to include this area in the resection to achieve seizure freedom. Using modern neurosurgical techniques, insular epilepsy surgery has proved to be safe and beneficial, making the “true” role of the insula in TLE surgery failures more relevant to understand. Further studies are needed to evaluate the efficacy of multilobar resections in patients with temporal plus epilepsy, in particular, when eloquent or difficult to access areas such as insula are suspected to be involved.
Increased risk of many early-life diseases after surgical removal of adenoids and tonsils in childhood
Authors: Byars Sean G. , Stearns Stephen C. , Boomsma Jacobus J.
Published: July 2017

BACKGROUND

Surgical removal of the adenoids and tonsils are common pediatric procedures, with conventional wisdom suggesting their absence has little impact on health or disease. However, little is known about long-term health consequences beyond the perioperative risks. Such ignorance is significant, for these lymphatic organs play important roles in both the development and the function of the immune system.

METHODS

We tested the long-term consequences of surgery in the population of Denmark by examining risk for 28 diseases with ̴1 million individuals followed from birth up to 30 years of age depending on whether any of three common surgeries (adenoidectomy, tonsillectomy, adenotonsillectomy) occurred in the first 9 years of life. To weigh costs and benefits, we also compared the absolute risks for these diseases to the risks for the conditions that these surgeries aimed to treat. We obtained robust results by using stratified Cox regressions with statistically well-powered samples of cases (with surgery) and controls (without surgery) whose general health was no different prior to surgery. We adjusted our estimates of risk for diseases occurring before surgery, stratified for sex (and other effects) and for 18 covariates, including parental disease history and birth metrics.

RESULTS

We found significantly elevated relative risks for many diseases, with effects on respiratory, allergic and infectious disorders after removal of adenoids and tonsils being most pronounced. For some of these diseases, absolute risk increases were considerable. In comparison, many risks for conditions that surgeries aimed to treat were either not significantly different or significantly higher following surgery up to 30 years of age. This suggests that any immediate benefits of these surgeries may not continue longer-term, while resulting in slightly compromised early adult health due to significantly increased risk of many non-target diseases.

CONCLUSIONS

Our results indicate that surgical removal of tonsils and adenoids early in life are associated with longer-term health risks. They underline the importance of these organs and tissues for normal immune functioning and early immune development, and suggest that these longer-term disease risks may outweigh the short-term benefits of these surgeries.
“Unexpected mutations after CRISPR-Cas9 editingin vivo” are most likely pre-existing sequence variants and not nuclease-induced mutations
Authors: Lareau Caleb A. , Clement Kendell , Hsu Jonathan Y. , Pattanayak Vikram , Joung J. Keith , Aryee Martin J. , Pinello Luca
Published: July 2017

Schaeferet al. recently advanced the provocative conclusion that CRISPR-Cas9 nuclease can induce off-target alterations at genomic loci that do not resemble the intended on-target site.1Using high-coverage whole genome sequencing (WGS), these authors reported finding SNPs and indels in two CRISPR-Cas9-treated mice that were not present in a single untreated control mouse. On the basis of this association, Schaeferet al. concluded that these sequence variants were caused by CRISPR-Cas9. This new proposed CRISPR-Cas9 off-target activity runs contrary to previously published work2–8and, if the authors are correct, could have profound implications for research and therapeutic applications. Here, we demonstrate that the simplest interpretation of Schaeferet al.’sdata is that the two CRISPR-Cas9-treated mice are actually more closely related genetically to each other than to the control mouse. This strongly suggests that the so-called “unexpected mutations” simply represent SNPs and indels shared in common by these mice prior to nuclease treatment. In addition, given the genomic and sequence distribution profiles of these variants, we show that it is challenging to explain how CRISPR-Cas9 might be expected to induce such changes. Finally, we argue that the lack of appropriate controls in Schaeferet al.’sexperimental design precludes assignment of causality to CRISPR-Cas9. Given these substantial issues, we urge Schaeferet al. to revise or re-state the original conclusions of their published work so as to avoid leaving misleading and unsupported statements to persist in the literature.
Effects of autozygosity and schizophrenia polygenic risk on cognitive and brain developmental trajectories
Authors: Cordova-Palomera Aldo , Kaufmann Tobias , Bettella Francesco , Wang Yunpeng , Doan Nhat Trung , Meer Dennis van der , Alnæs Dag , Rokicki Jaroslav , Moberget Torgeir , Sønderby Ida Elken , Andreassen Ole A. , Westlye Lars T.
Published: July 2017

Cognitive and brain development are determined by dynamic interactions between genes and environment across the lifespan. Aside from marker-by-marker analyses of polymorphisms, biologically meaningful features of the whole-genome (derived from the combined effect of individual markers) have been postulated to inform on human phenotypes including cognitive traits and their underlying biological substrate.

Here, estimates of inbreeding and genetic susceptibility for schizophrenia calculated from genome-wide data –runs of homozygosity (ROH) and schizophrenia polygenic risk score (PGRS)– are analyzed in relation to cognitive abilities (n=4183) and brain structure (n=516) in a general-population sample of European-ancestry participants aged 8-22, from the Philadelphia Neurodevelopmental Cohort.

The findings suggest that a higher ROH burden and higher schizophrenia PGRS are associated with higher intelligence. Cognition~ROH and cognition~PGRS associations obtained in this cohort may respectively evidence that assortative mating influences intelligence, and that individuals with high schizophrenia genetic risk who do not transition to disease status are cognitively resilient.

Neuroanatomical data showed that the effects of schizophrenia PGRS on cognition could be modulated by brain structure, although larger imaging datasets are needed to accurately disentangle the underlying neural mechanisms linking IQ with both inbreeding and the genetic burden for schizophrenia.
Statistically robust methylation calling for whole-transcriptome bisulfite sequencing reveals distinct methylation patterns for mouse RNAs
Authors: Legrand Carine , Tuorto Francesca , Hartmann Mark , Liebers Reinhard , Jacob Dominik , Helm Mark , Lyko Frank
Published: July 2017

Cytosine-5 RNA methylation plays an important role in several biologically and pathologically relevant processes. However, owing to methodological limitations, the transcriptome-wide distribution of this mark has remained largely unknown. We previously established RNA bisulfite sequencing as a method for the analysis of RNA cytosine-5 methylation patterns at single-base resolution. More recently, next-generation sequencing has provided opportunities to establish transcriptome-wide maps of this modification. Here, we present a computational approach that integrates tailored filtering and data-driven statistical modeling to eliminate many of the artifacts that are known to be associated with bisulfite sequencing. By using RNAs from mouse embryonic stem cells, we performed a comprehensive methylation analysis of mouse tRNAs, rRNAs, and mRNAs. Our approach identified all known methylation marks in tRNA and two previously unknown but evolutionary conserved marks in 28S rRNA. In addition, mRNAs were found to be very sparsely methylated or not methylated at all. Finally, the tRNA-specific activity of the DNMT2 methyltransferase could be resolved at single-base resolution, which provided important further validation. Our approach can be used to profile cytosine-5 RNA methylation patterns in many experimental contexts and will be important for understanding the function of cytosine-5 RNA methylation in RNA biology and in human disease.