bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Chronic Spinal Pain
Authors: Sharan Ashwini , Riley Jonathan , Hoelscher Christian
Published: April 2017

Study Design.

Topic overview.

Objective.

To describe the varied etiologies resulting in chronic spinal pain and review the current available evidence for treatments.

Summary of Background Data.

Chronic pain conditions, especially those that affect the axial back and radiate to the extremities, affect a large population. This results in pronounced disability and a high socioeconomic burden. Our understanding of the underlying mechanisms for chronic pain is limited. This prevents a comprehensive diagnostic approach. Evidence from high-level clinical trials supporting treatments for chronic spinal pain is also limited.

Methods.

Articles were identified through PubMed searches or already known to the author. The literature was reviewed and summarized, indicating the strength of evidence available for many treatment modalities.

Results.

There are very few studies published that evaluate behavioral modifications for chronic spinal pain and only one long-term study investigating chronic pharmacological treatments. The data on the success of spinal surgeries to relieve chronic spinal pain suggest an unacceptably high failure rate. The best evidence (Level I) currently available suggests that spinal cord stimulation is a safe, effective, and durable treatment for chronic spinal pain. Recent clinical data support further investigation of new innovations and earlier therapeutic consideration of currently employed approaches.

Conclusion.

Currently, physicians are limited in the practice of evidence-based medicine regarding chronic spinal pain treatments due to both the paucity of data available and an inconsistent diagnostic nomenclature. The introduction of new neurostimulation modalities is promising but requires better characterization through ongoing prospective clinical investigation.

Level of Evidence: 5
Complications of the Top 10 Foot and Ankle Procedures Cared for by Newly Trained Orthopedists in the United States
Authors: Hunter Joshua G. , Olsen Joshua R. , Anglen Jeffrey , DiGiovanni Christopher W. , Baumhauer Judith
Published: April 2017

Quality perioperative management encompasses 2 primary goals: treatment efficacy and patient safety. Central to patient safety is protection from adverse outcome, and entails reduction of complications. The purpose of this study was to accurately identify the most common complications and characterize their incidence to better direct current practice improvement initiatives and preventative care. We searched the American Board of Orthopaedic Surgeons database from January 2006 to December 2010 for the most commonly performed foot and ankle procedures as indicated by CPT codes (27600-28899; 29893-29907). The 10 most frequently performed procedures were identified and the “Surgical (or Medical) Unspecified” free text associated with each complication was read, interpreted, categorized, and tallied. We quantified the incidence of complications associated with (a) each procedure individually; (b) for the 10 most common procedures; and (c) for all procedures cumulatively. A total of 56,786 total foot and ankle codes were reported by 2970 orthopedic surgeons seeking certification. The 10 most commonly reported procedures accounted for 46% of all CPT codes logged. Infection was the most common overall complication (3.7%) and the most often reported adverse event among 9 of the top 10 procedures performed. Improving patient safety and avoiding adverse events requires an accurate picture of the incidence of complications after individual procedures that can be used to design customized risk-reduction programs and monitor their successive impact. Comprehensive databases can be a valuable tool to enhance practice improvement within the Maintenance of Certification initiative.

Level of Evidence: Diagnostic Level III—retrospective review. See Instructions for Authors for a complete description of levels of evidence.
Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic Nerve Pacing Catheter
Authors: Reynolds Steven , Ebner Adrian , Meffen Tracy , Thakkar Viral , Gani Matt , Taylor Kaity , Clark Linda , Sadarangani Gautam , Meyyappan Ramasamy , Sandoval Rodrigo , Rohrs Elizabeth , Hoffer Joaquín A.
Published: April 2017

Objectives:

Over 30% of critically ill patients on positive-pressure mechanical ventilation have difficulty weaning from the ventilator, many of whom acquire ventilator-induced diaphragm dysfunction. Temporary transvenous phrenic nerve pacing using a novel electrode-bearing catheter may provide a means to prevent diaphragm atrophy, to strengthen an atrophied diaphragm, and mitigate the harms of mechanical ventilation. We tested the initial safety, feasibility, and impact on ventilation of this novel approach.

Design:

First-in-Humans case series.

Setting:

Angiogram suite.

Patients:

Twenty-four sedated, mechanically ventilated patients immediately prior to an elective atrial septal defect repair procedure.

Interventions:

A 9.5-Fr central venous catheter with 19 embedded electrodes was placed via Seldinger technique into the left subclavian vein and superior vena cava and evaluated for up to 90 minutes. The electrode combinations determined to provide best transvenous stimulation of the right and left phrenic nerves were activated in synchrony with mechanically ventilated breaths.

Measurements and Main Results:

One patient could not be tested for reasons unrelated to the device. In the 23 patients who underwent the full protocol, transvenous stimulation activated the diaphragm in 22 of 23 (96%) left phrenic capture attempts and 20 of 23 (87%) right phrenic capture attempts. In one subject, a congenital left-sided superior vena cava precluded right-sided capture. Significant reductions in ventilator pressure-time-product were achieved during stimulation assisted breaths in all 22 paced subjects (range, 9.9–48.6%; p < 0.001). There were no adverse events either immediately or at 2-week follow-up.

Conclusions:

In this First-in-Human series, diaphragm pacing with a temporary catheter was safe and effectively contributed to ventilation in conjunction with a mechanical ventilator.
Atriobronchial Fistula Complicated by Septic Cerebral Air Emboli After Pulmonary Vein Ablation
Authors: Velghe David , Apers Thomas , Devriendt Stefanie , Deblier Ivo , Hendriks Bart , Nieuwendijk Rogier , Rogiers Peter
Published: April 2017

Objective:

To describe a case of an infected atriobronchial fistula as a late complication after pulmonary vein ablation, leading to septic air emboli and requiring urgent cardiac surgery.

Data Sources:

Clinical observation.

Study Selection:

Case report.

Data Extraction:

Relevant clinical information. PubMed was searched for relevant literature.

Data Synthesis:

Given its high success and low complication rate, pulmonary vein isolation is expected to be increasingly performed worldwide. Despite its success, some of its rare complications are potentially devastating and are difficult to diagnose early. In this report, we present the case of a 32-year-old woman, who was readmitted to hospital 2 months after pulmonary vein ablation. The clinical picture resembled meningococcemia with spreading petechiae on legs and arms raising concern for Waterhouse-Friderichsen syndrome. Further echocardiographic investigation led to the discovery of massive amounts of intracardiac air which demanded urgent lung isolation and sternotomy. Intraoperatively a small infected left atrial perforation was oversewn and a fistula to the right main bronchus was closed by means of an autologous pericardial patch. One month later, still revalidating, she could be discharged home with only minor neurologic sequelae.

Conclusions:

Clinicians should be aware of the dramatic complications of invasive antiarrhythmic procedures and their atypical and late presentations. Better preprocedural appreciation of cardiac wall thickness, early echocardiographic diagnosis, and swift referral for cardiac surgery might impact outcome dramatically.
Activation of the CXCR4 chemokine receptor enhances biological functions associated with B16 melanoma liver metastasis
Authors: Mendt Mayela , Cardier Jose E.
Published: April 2017

The CXCR4 chemokine receptor plays an essential role in the homing of cells to organs expressing its ligand, CXCL12. CXCR4 expressed on tumor cells might regulate their traffic during metastasis. Here, we investigated whether the activation of CXCR4 on B16 murine melanoma cells regulates biological functions associated with metastasis, in vitro and in vivo. Flow cytometry and PCR analysis showed that B16 constitutively expresses high levels of CXCR4 (CXCR4-B16). Biological assays showed that the activation of CXCR4, by its ligand CXCL12, increases the migration, invasion, and proliferation of CXCR4-B16. AMD3100 significantly inhibited the stimulatory migrating effect induced by CXCL12. Treatment of CXCR4-B16 with CXCL12 increases their adhesion to liver sinusoidal endothelial cell (LSEC) monolayers. LSEC, expressing CXCL12, increased the migration of CXCR4-B16. In a liver metastasis model, CXCR4-B16 metastasis was associated with an increased expression of CXCL12 in LSEC territories. CXCR4-B16 cells were located close to LSEC microenvironments expressing CXCL12. Increased liver metastasis was observed after injecting CXCR4-B16 cells previously treated with CXCL12. Our results provide evidence showing that CXCR4 plays an important role in regulating biological functions associated with B16 liver metastasis.
Adnexal Carcinomas Treated With Mohs Micrographic Surgery: A Comprehensive Review
Authors: Tolkachjov Stanislav N.
Published: April 2017

BACKGROUND

Adnexal carcinomas (ACs) are rare cutaneous malignancies of sweat gland or pilosebaceous origin. Optimal treatment and metastatic potential of AC are poorly defined. Mohs micrographic surgery (MMS) has been increasingly used to treat AC.

OBJECTIVE

To review selected primary cutaneous AC and their treatment outcomes with MMS.

MATERIALS AND METHODS

Literature review using PubMed search for articles related to primary cutaneous ACs.

RESULTS

Sebaceous carcinoma treated with MMS recurred and metastasized in 6.4% and 3.7%, respectively. Primary cutaneous mucinous carcinoma treated with MMS recurred and metastasized in 9.6% and 6.4%, respectively. After MMS, 4.7% of microcystic AC recurred with no reported metastases. After MMS, recurrences and metastases of trichilemmal carcinoma or hidradenocarcinoma have not been reported. Two (4.2%) regional lymph node metastases but no distant metastases or local recurrences have been reported in eccrine porocarcinoma. Squamoid eccrine duct tumor, pilomatrix carcinoma, and spiradenocarcinoma treated with MMS are also reviewed.

CONCLUSION

The rarity of ACs and the lack of comparative data on treatment makes conclusive recommendations on treatment difficult. Recent large case series and reviews suggest MMS is a useful and possibly superior treatment for AC and should be considered if primary cutaneous disease is suspected.
Examination of the relationship between management and clinician perception of patient safety climate and patient satisfaction
Authors: Mazurenko Olena , Richter Jason , Kazley Abby Swanson , Ford Eric
Published: April 2017

Purpose:

The aim of this study was to explore the relationship between managers and clinicians' agreement on deeming the patient safety climate as high or low and the patients' satisfaction with those organizations.

Data Sources/Study Setting:

We used two secondary data sets: the Hospital Survey on Patient Safety Culture (2012) and the Hospital Consumer Assessment of Healthcare Providers and Systems (2012).

Methodology/Approach:

We used ordinary least squares regressions to analyze the relationship between the extent of agreement between managers and clinicians' perceptions of safety climate in relationship to patient satisfaction. The dependent variables were four Hospital Consumer Assessment of Healthcare Providers and Systems patient satisfaction scores: communication with nurses, communication with doctors, communication about medicines, and discharge information. The main independent variables were four groups that were formed based on the extent of managers and clinicians' agreement on four patient safety climate domains: communication openness, feedback and communication about errors, teamwork within units, and teamwork across units.

Findings:

After controlling for hospital and market-level characteristics, we found that patient satisfaction was significantly higher if managers and clinicians reported that patient safety climate is high or if only clinicians perceived the climate as high. Specifically, manager and clinician agreement on high levels of communication openness (β = 2.25, p = .01; β = 2.46, p = .05), feedback and communication about errors (β = 3.0, p = .001; β = 2.89, p = .01), and teamwork across units (β = 2.91, p = .001; β = 3.34, p = .01) was positively and significantly associated with patient satisfaction with discharge information and communication about medication. In addition, more favorable perceptions about patient safety climate by clinicians only yielded similar findings.

Practice Implications:

Organizations should measure and examine patient safety climate from multiple perspectives and be aware that individuals may have varying opinions about safety climate. Hospitals should encourage multidisciplinary collaboration given that staff perceptions about patient safety climate may be associated with patient satisfaction.
LABORATORY EVALUATION OF HYPERCOAGULABLE STATES IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION WHO ARE LESS THAN 56 YEARS OF AGE
Authors: Liu Qingyun , Lahey J. Michael , Karlen Rachel , Stewart Jay M.
Published: April 2017

Purpose:

To investigate whether the results of early tests for hypercoagulability are correlated with the development of central retinal vein occlusion risk factors later in life and to evaluate the necessity of these tests in younger patients.

Methods:

This was a retrospective, observational case series. From January 1995 to December 2014, 55 patients aged below 56 years with central retinal vein occlusion (CRVO) were enrolled in the study. Laboratory evaluations for homocysteine, activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies were obtained at the onset of CRVO. After 24 to 205 months, the presence of risk factors for CRVO such as hypertension, obesity, hyperlipidemia, diabetes mellitus, sleep apnea, and glaucoma was determined. Bilateral correlation and logistic regression were performed to determine the correlations between the results of the initial laboratory tests and the diagnosis of CRVO risk factors.

Results:

The median follow-up was 168.5 months. Five patients completed at least 24 months of follow-up, 9 patients completed at least 5 years, and 36 patients completed at least 10 years. Five patients had no or less than 24 months' follow-up. Fourteen of 50 patients (28%) had at least one positive test result at the onset of CRVO. At the end of follow-up, 11 patients had been diagnosed with obesity (22%), 29 with hypertension (58%), 21 with hyperlipidemia (42%), 24 with diabetes (8%), 5 with sleep apnea (10%), and 8 with glaucoma (16%). Among 36 patients with a minimum 10 years' follow-up, 30 (83%) developed at least one common risk factor, and none experienced any thromboembolic events. There were no correlations between test results and the diagnosis of any risk factors in patients with a minimum of 2, 5, or 10 years' follow-up (P > 0.05).

Conclusion:

The results of laboratory tests evaluating hypercoagulability in young patients with CRVO are not correlated with later-developed commonly known risk factors. Many of the common risk factors were present by the end of the study, suggesting that they still remain the core etiology for the disease. The value of the thrombophilic tests is brought into question, as none of the patients demonstrated further clotting or any unusual thrombi with long-term follow-up.
Enteric Fever in Children in Western Sydney, Australia, 2003–2015
Authors: Khatami Ameneh , Khan Fouzia , Macartney Kristine K.
Published: April 2017

Background:

Enteric fever is a vaccine-preventable disease with cases in Australia predominantly acquired overseas. The aim of this study was to define the burden of enteric fever in children presenting to a pediatric hospital in Western Sydney between 2003 and 2015.

Methods:

Cases between January 2003 and December 2013 were ascertained through medical records using International Classification of Disease–coded discharge diagnoses, cross-referenced with microbiology laboratory data for all isolates of Salmonella enterica serovar typhi and S. enterica serovar paratyphi. Prospective cases from January 2014 to April 2015 were additionally captured through records maintained by the infectious diseases team.

Results:

Seventy-one cases of enteric fever were identified in 12.3 years with an average of 4 cases per year between 2003 and 2008 and 7 cases per year between 2009 and 2014. Two were visitors to Australia, 8 were recent migrants, and 59 were Australian residents returning from overseas travel. Two children had no history of overseas travel. Countries of travel predominantly included the Indian subcontinent (60/69) and Southeast Asia (7/69). Of 30 children with information available on pretravel medical consultation, 1 was offered and received typhoid vaccine. Ninety-four percent of children (67) required admission for 1–28 days (median: 5 days). Three children required readmission, with 1 case of presumed relapse. Ninety percent (64) were diagnosed by blood or stool culture with S. enterica serovar typhi the predominant organism (54/64).

Conclusions:

In Australia, hospitalizations for pediatric enteric fever appear to be increasing; predominantly occurring in Australian-resident children. Greater awareness and education are required for parents and clinicians regarding travel health risks and prevention strategies.
Long-term follow-up of patients with chronic hepatitis C treated with α-interferon and ribavirin antiviral therapy: clinical and fibrosis impact of treatment response
Authors: Cordero-Ruiz Patricia , Carmona-Soria Isabel , Rodríguez-Téllez Manuel , Caunedo-Alvarez Angel , Quezada-Pacheco Roberto H. , Flores-Cucho Alexander , Romero-Gómez Manuel , Vilches-Arenas Ángel
Published: April 2017

Background and goals

The slow progression of chronic hepatitis C (CHC) infection requires long observation periods to detect clinical changes. We compare the incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality, liver-related mortality, and fibrosis progression between patients with a sustained virological response (SVR) and nonresponders (NR) after a 13-year follow-up period.

Study

One hundred and eighty-two CHC patients, who received interferon and ribavirin treatment between 1996 and 2000, were included. Clinical events were evaluated during follow-up. At the end of follow-up, transient elastography was used to assess fibrosis progression.

Results

Of the 182 patients, 46.7% (n=85) achieved an SVR. Twenty-seven patients developed hepatic decompensation (one SVR) and 15 developed HCC (three SVR). Twenty-nine patients died (eight SVR). Twelve of the 29 deaths were liver related (two SVR). Independent factors associated with hepatic decompensation were NR to treatment [hazard ratio (HR)=23.35; 95% confidence interval (CI): 2.90–189.25; P=0.003], advanced fibrosis at baseline (HR=9.11; 95% CI: 4.13–20.09), and treatment delay after diagnosis (HR=1.02; 95% CI: 1.00–1.03; P=0.012). Only the latter two were associated with HCC development and liver-related mortality. An assessment of liver fibrosis was performed on 125 patients (66 SVR). Fibrosis values were significantly lower in SVR patients, showing less progression to advanced stages of fibrosis [SVR: 6.6 (2.8); 95% CI: 5.8–7.3] than NR [NR: 14.0 (11.1); 95% CI: 11.1–16.9; P<0.001].

Conclusion

In patients with CHC, SVR is durable and reduces clinical events. The risk of HCC development is lower, but not eliminated. Sustained responders showed fibrosis stabilization or improved fibrosis values.
Acceptance in chronic neck pain: associations with disability and fear avoidance beliefs
Authors: Thompson Dave P. , Woby Steve R.
Published: April 2017

Chronic neck pain can result in significant levels of disability. Physiotherapy treatments often aim to modify cognitive factors and this approach benefits some, but not all, patients. Research from other pain conditions suggests that acceptance may be related to disability; however, it is unclear whether these associations exist in patients with neck pain. Moreover, it is unclear to what extent other cognitive factors are related to acceptance. Feasibly, if these factors are related, existing treatments may already be indirectly modifying acceptance. The aim of this study was therefore to establish the associations between acceptance and disability, and between acceptance and other cognitive factors. Cross-sectional data were collected from 149 patients and regression analyses were carried out. In the first analysis, disability was the dependent variable and the proportion of variance explained by two acceptance subscales (activities engagement and pain willingness) was calculated. In the second analyses, the acceptance subscales were the dependent variables. Measures of pain-related fear, catastrophizing and pain vigilance and awareness were entered as explanatory variables and the proportion of variance explained was calculated. In the first analysis, acceptance explained 18% of variance in disability (P<0.001). In the second analysis, cognitive factors explained 7% (P<0.05) of variance in activities engagement and 58% (P<0.001) of pain willingness. On this basis, treatments that enhance acceptance may reduce disability. Moreover, as cognitive factors were strongly related to pain willingness, but not activity engagement, alternative treatments may be required to maximize acceptance. Further studies are warranted to assess acceptance-based treatments in patients with neck pain.
Emergency Department Management of Bronchiolitis in the United States
Authors: Gong Constance , Byczkowski Terri , McAneney Constance , Goyal Monika K. , Florin Todd A.
Published: April 2017

Objective

The aim of this study was to examine differences between general and pediatric emergency departments (PEDs) in adherence to the American Academy of Pediatrics bronchiolitis management guidelines.

Methods

We conducted a nationally representative study of ED visits by infants younger than 24 months with bronchiolitis from 2002 to 2011 using the National Hospital Ambulatory Medical Care Survey. Diagnostic testing (complete blood counts, radiographs) and medication use (albuterol, corticosteroids, antibiotics and intravenous fluids) in general emergency departments (GEDs) were compared with those in PEDs before and after 2006 American Academy of Pediatrics guideline publication. Weighted percentages were compared, and logistic regression evaluated the association between ED type and resource use.

Results

Of more than 2.5 million ED visits for bronchiolitis from 2002 to 2011, 77.3% occurred in GEDs. General emergency departments were more likely to use radiography (62.7% vs 42.1%; adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.4–4.1), antibiotics (41.3% vs 18.8%; aOR, 2.8; 95% CI, 1.5–5.2), and corticosteroids (24.3% vs 12.5%; aOR, 2.1; 95% CI, 1.0–4.5) compared with PEDs. Compared with preguideline, after guideline publication PEDs had a greater decrease in radiography use (−19.7%; 95% CI, −39.3% to −0.03%) compared with GEDs (−12.2%; 95% CI, −22.3% to −2.1%), and PEDs showed a significant decline in corticosteroid use (−12.4%; 95% CI, −22.1% to −2.8%), whereas GEDs showed no significant decline (−4.6%; 95% CI, −13.5% to 4.3%).

Conclusions

The majority of ED visits for bronchiolitis in the United States occurred in GEDs, yet GEDs had increased use of radiography, corticosteroids, and antibiotics and did not show substantial declines with national guideline publication. Given that national guidelines discourage the use of such tests and treatments in the management of bronchiolitis, efforts are required to decrease ED use of these resources in infants with bronchiolitis, particularly in GEDs.
Pelvic Inflammatory Disease in a Pediatric Emergency Department
Authors: Solomon Michelle , Tuchman Lisa , Hayes Katie , Badolato Gia , Goyal Monika K.
Published: April 2017

Objectives

Most adolescent cases of pelvic inflammatory disease (PID) are diagnosed in the emergency department (ED). An important step to prevent PID-related morbidity among this high-risk population is to quantify prevalence and microbial patterns and identify testing and treatment gaps.

Methods

We performed a retrospective, cross-sectional study of all visits by adolescents to an urban children's ED with an International Classification of Diseases, Ninth Revision, diagnosis of PID in 2012. We used standard descriptive statistics to quantify PID diagnoses, sexually transmitted infections (STI) testing, and treatment.

Results

Pelvic inflammatory disease was diagnosed in more than 9% of women with a chief complaint of abdominal/pelvic pain. Most diagnosed cases underwent some STI testing, and 40% tested positive. Seventy percent of cases received antibiotics recommended by the Centers for Disease Control and Prevention.

Conclusions

There is a high prevalence of PID among adolescents in the pediatric ED. Rates of STI testing and appropriate treatment reveal gaps in diagnosis and management, representing a lost opportunity for identification and treatment of PID/STIs among high-risk adolescents.
Traumatic Abdominal Wall Hernia in Children by Handlebar Injury: When to Suspect, Scan, and Call the Surgeon
Authors: Rinaldi Victoria Elisa , Bertozzi Mirko , Magrini Elisa , Riccioni Sara , Di Cara Giuseppe , Appignani Antonino
Published: April 2017

Traumatic abdominal wall hernias (TAWHs) can be defined as a herniation through disrupted musculature and fascia associated with blunt trauma. They are seen in approximately 1% of patients with blunt abdominal trauma. Data on TAWH in the pediatric population are very limited and principally based on case reports and a few case series. Past reports have indicated that the presence of the “handlebar sign” confers an increased risk of internal injury. Concomitant internal injuries are reported with an incidence between 25% and 70%, and occult hernias may also occur and are usually detected only by abdominal computed tomography scan and ultrasonography. The treatment of TAWH consists in surgical exploration through closure of the defect. We describe 2 cases of TAWH due to blunt impact by bicycle handlebars that occurred in our department with a brief literature review. Our objectives are to describe the variable clinical presentations and management of these events. We hope to provide a useful tool for the clinician to increase early clinical suspicion and detection of this insidious injury.
Emergency Point-of-Care Ultrasound Diagnosis of Retained Soft Tissue Foreign Bodies in the Pediatric Emergency Department
Authors: Varshney Terry , Kwan Charisse W. , Fischer Jason W. , Abo Alyssa
Published: April 2017

The presence of a foreign body (FB), its depth and size, is often indeterminate by clinical examination. Conventional imaging such as a radiograph can fail to visualize soft tissue FBs. We present 2 cases where point-of-care ultrasound was used to detect previously unidentified FBs.
Phonetic characteristics of vocalizations during pain
Authors: Lautenbacher Stefan , Salinas-Ranneberg Melissa , Niebuhr Oliver , Kunz Miriam
Published: April 2017

Introduction and Objectives:

There have, yet, been only few attempts to phonetically characterize the vocalizations of pain, although there is wide agreement that moaning, groaning, or other nonverbal utterance can be indicative of pain. We studied the production of vowels “u,” “a,” “i”, and “schwa” (central vowel, sounding like a darker “e” as in hesitations like “ehm”)—as experimental approximations to natural vocalizations.

Methods:

In 50 students vowel production and self-report ratings were assessed during painful and nonpainful heat stimulation (hot water immersion) as well as during baseline (no-stimulation). The phonetic parameters extracted were pitch (mean F0), phonatory fluctuations (range F0) and loudness (acoustic energy level).

Results:

Only for the vowels “u” and “schwa,” which might be considered best approximations to moaning and groaning, did pitch and loudness increase during pain. Furthermore, changes from nonpainful to painful stimulations in these parameters also significantly predicted concurrent changes in pain ratings.

Conclusion:

Vocalization characteristics of pain seem to be best described by an increase in pitch and in loudness. Future studies using more specific and comprehensive phonetic analyses will surely help to provide an even more precise characterization of vocalizations because of pain.
Role of Family in the Process of Rehabilitation of Older Adults Hospitalized in a Nursing Home
Authors: Szczepańska-Gieracha Joanna , Kowalska Joanna , Salamon-Krakowska Katarzyna , Ochnik Magdalena , Jaworska-Burzyńska Lilianna
Published: April 2017

The study involved 39 patients aged 76.0 (SD = 10.9) years (minimum 47 years, maximum 91 years). The examined patients came from families with varying degrees of caring capacity and, on these grounds, were assigned into subgroups. We used Mini-Mental State Examination, the Geriatric Depression Scale, and the Barthel Index. The greatest improvement in functional status after rehabilitation occurred in patients with a family characterized by a lack of caring capacity, and the smallest improvement was in the group of patients with full caring capacity. The greatest improvements in the performance of basic activities of daily living were reported in singles or people from families with a total lack of care.
A Review of the Evidence for the Influence of Maternal Long-Chain Omega-3 Fatty Acid Intake on Atopy in Offspring
Authors: Loveless Amanda
Published: April 2017

Atopic disease has been on the rise in the United States and worldwide. Speculation is that the immune system plays a role in its development in utero. The purpose of this review is to evaluate the strength of available evidence supporting or refuting the impact of maternal long-chain omega-3 status on atopy development in offspring. After reviewing 21 primary articles, the evidence shows a potential for omega-3 fatty acids to influence immune system development in utero and subsequent atopy in offspring. More randomized controlled trials are needed to confirm these findings, with attention to the confounding variables.
Effects of conservation management of landscapes and vertebrate communities on Lyme borreliosis risk in the United Kingdom
Authors: Millins Caroline , Gilbert Lucy , Medlock Jolyon , Hansford Kayleigh , Thompson Des BA , Biek Roman
Published: April 2017

Landscape change and altered host abundance are major drivers of zoonotic pathogen emergence. Conservation and biodiversity management of landscapes and vertebrate communities can have secondary effects on vector-borne pathogen transmission that are important to assess. Here we review the potential implications of these activities on the risk of Lyme borreliosis in the United Kingdom. Conservation management activities include woodland expansion, management and restoration, deer management, urban greening and the release and culling of non-native species. Available evidence suggests that increasing woodland extent, implementing biodiversity policies that encourage ecotonal habitat and urban greening can increase the risk of Lyme borreliosis by increasing suitable habitat for hosts and the tick vectors. However, this can depend on whether deer population management is carried out as part of these conservation activities. Exclusion fencing or culling deer to low densities can decrease tick abundance and Lyme borreliosis risk. As management actions often constitute large-scale perturbation experiments, these hold great potential to understand underlying drivers of tick and pathogen dynamics. We recommend integrating monitoring of ticks and the risk of tick-borne pathogens with conservation management activities. This would help fill knowledge gaps and the production of best practice guidelines to reduce risks.

This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.
Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk
Authors: Hosseini Parviez R. , Mills James N. , Prieur-Richard Anne-Hélène , Ezenwa Vanessa O. , Bailly Xavier , Rizzoli Annapaola , Suzán Gerardo , Vittecoq Marion , García-Peña Gabriel E. , Daszak Peter , Guégan Jean-François , Roche Benjamin
Published: April 2017

Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts.

This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.
A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease
Authors: Martin DDO , Kay C , Collins JA , Nguyen YT , Slama RA , Hayden MR
Published: April 2017

Post-translational modifications (PTMs) are key modulators of protein function. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene. A spectrum of PTMs have been shown to modify the normal functions of HTT, including proteolysis, phosphorylation and lipidation, but the full contribution of these PTMs to the molecular pathogenesis of HD remains unclear. In this study, we examine all commonly occurring missense mutations inHTTto identify potential human modifiers of HTT PTMs relevant to HD biology. We reveal a SNP that modifies post-translational myristoylation of HTT, resulting in downstream alterations to toxic HTT proteolysis in human cells. This is the first SNP shown to functionally modify a PTM in HD and the first validated genetic modifier of post-translational myristoylation. This SNP is a high-priority candidate modifier of HD phenotypes and may illuminate HD biology in human studies.
Unexpected sequences and structures of mtDNA required for efficient transcription from the first heavy-strand promoter
Authors: Uchida Akira , Murugesapillai Divakaran , Wang Yao , Lodeiro Maria F. , Prabhakar Shaan , Arnold Jamie J. , Maher L. James , Williams Mark C. , Cameron Craig E.
Published: April 2017

Human mtDNA contains three promoters, suggesting a need for differential expression of the mitochondrial genome. Studies of mitochondrial transcription have used a reductionist approach, perhaps masking differential regulation. Here we evaluate transcription from light-strand (LSP) and heavy-strand (HSP1) promoters using templates that mimic their natural context. These studies reveal sequences upstream, hypervariable in the human population (HVR3), and downstream of the HSP1 transcription start site required for maximal yield. The carboxy-terminal tail of TFAM is essential for activation of HSP1 but not LSP. Images of the template obtained by atomic force microscopy show that TFAM creates loops in a discrete region, the formation of which correlates with activation of HSP1; looping is lost in tail-deleted TFAM. Identification of HVR3 as a transcriptional regulatory element may contribute to between-individual variability in mitochondrial gene expression. The unique requirement of HSP1 for the TFAM tail may enable its regulation by post-translational modifications.
Dynactin binding to tyrosinated microtubules promotes centrosome centration inC. elegansby enhancing dynein-mediated organelle transport
Authors: Barbosa Daniel José , Duro Joana , Cheerambathur Dhanya K. , Prevo Bram , Carvalho Ana Xavier , Gassmann Reto
Published: April 2017

The microtubule-based motor dynein generates pulling forces for centrosome centration and mitotic spindle positioning in animal cells. How the essential dynein activator dynactin regulates these functions of the motor is incompletely understood. Here, we dissect the role of dynactin’s microtubule binding activity, located in p150’s CAP-Gly domain and an adjacent basic patch, in theC. eleganszygote. Using precise mutants engineered by genome editing, we show that microtubule tip tracking of dynein-dynactin is dispensable for targeting the motor to the cell cortex and for generating cortical pulling forces. Instead, p150 CAP-Gly mutants inhibit cytoplasmic pulling forces responsible for centration of centrosomes and attached pronuclei. The centration defects are mimicked by mutations of the C-terminal tyrosine of α-tubulin, and both p150 CAP-Gly and tubulin tyrosination mutants decrease the frequency of organelle transport from the cell periphery towards centrosomes during centration. In light of recent work on dynein-dynactin motilityin vitro, our results suggest that p150 GAP-Gly domain binding to tyrosinated microtubules promotes initiation of dynein-mediated organelle transport in the dividing embryo, and that this function of dynactin is important for generating robust cytoplasmic pulling forces for centrosome centration.
Optimal information transfer in enzymatic networks: A field theoretic formulation
Authors: Samanta Himadri S. , Hinczewski Michael , Thirumalai D.
Published: April 2017

Signaling in enzymatic networks is typically triggered by environmental fluctuations, resulting in a series of stochastic chemical reactions, leading to corruption of the signal by noise. For example, information flow is initiated by binding of extracellular ligands to receptors, which is transmitted through a cascade involving kinase-phosphatase stochastic chemical reactions. For a class of such networks, we develop a general field-theoretic approach in order to calculate the error in signal transmission as a function of an appropriate control variable. Application of the theory to a simple push-pull network, a module in the kinase-phosphatase cascade, recovers the exact results for error in signal transmission previously obtained using umbral calculus (Phys. Rev. X.,4, 041017 (2014)). We illustrate the generality of the theory by studying the minimal errors in noise reduction in a reaction cascade with two connected push-pull modules. Such a cascade behaves as an effective three-species network with a pseudo intermediate. In this case, optimal information transfer, resulting in the smallest square of the error between the input and output, occurs with a time delay, which is given by the inverse of the decay rate of the pseudo intermediate. Surprisingly, in these examples the minimum error computed using simulations that take non-linearities and discrete nature of molecules into account coincides with the predictions of a linear theory. In contrast, there are substantial deviations between simulations and predictions of the linear theory in error in signal propagation in an enzymatic push-pull network for a certain range of parameters. Inclusion of second order perturbative corrections shows that differences between simulations and theoretical predictions are minimized. Our study establishes that a field theoretic formulation of stochastic biological signaling offers a systematic way to understand error propagation in networks of arbitrary complexity.
A versatile genetic tool for post-translational control of gene expression inDrosophila melanogaster
Authors: Sethi Sachin , Wang Jing W.
Published: April 2017

Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed forin vivostudies inDrosophilais limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to controlin vivogene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations.
Chimeric 14-3-3 proteins for unravelling interactions with intrinsically disordered partners
Authors: Sluchanko Nikolai N. , Tugaeva Kristina V. , Antson Alfred A.
Published: April 2017

In eukaryotes, several proteins act as “hubs”, integrating signals from a variety of interacting partners that bind to the hub through intrinsically disordered regions. Not surprisingly, one of the major hubs, the 14-3-3 protein, that plays wide-ranging roles in cellular processes, has been linked with a number of disorders including neurodegenerative diseases and cancer. A partner protein usually binds with its phosphopeptide accommodated in an amphipathic groove (AG) of 14-3-3, a promising platform for therapeutic intervention. Protein plasticity in the groove allows to accommodate a range of phosphopeptides with different sequences. So far, in spite of mammoth effort, accurate structural information has been derived only for few 14-3-3 complexes with phosphopeptide-containing proteins or various short synthetic peptides. The progress has been prevented by intrinsic disorder of partner proteins and, in case of transient interactions, by the low affinity of phosphopeptides. We reasoned that these problems could be resolved by using chimeric 14-3-3 proteins with incorporated peptide sequences. We tested this hypothesis and found that such chimeric proteins are easy to design, express, purify and crystallize. We show that when attached to the C terminus of 14-3-3 via an optimal linker, peptides become stoichiometrically phosphorylated by protein kinase A during bacterial co-expression. We determined crystal structures for complexes of chimeric 14-3-3 protein fused with three different peptides. In most of the cases, the phosphopeptide is bound inside the AG, providing invaluable information on its interaction with the protein. This approach can reinvigorate studies of 14-3-3 protein complexes, including those with otherwise challenging low affinity phosphopeptides. Furthermore, 14-3-3-phosphopeptide chimeras can be useful for the design of novel biosensors forin vitroandin vivoimaging experiments.
Population size determines the type of nucleotide variations in humans
Authors: Subramanian Sankar
Published: April 2017

It is well known that the effective size of a population (Ne) is one of the major determinants of the amount of genetic variation within the population. Here, we examined whether the types of genetic variations are dictated by the effective population size. Our results revealed that for low frequency variants, the ratio of AT→GC to GC→AT variants (β) was similar across populations, suggesting the similarity of the pattern of mutation in various populations. However, for high frequency variants,βshowed a positive correlation with the effective population size of the populations. This suggests a much higher proportion of high frequency AT→GC variants in large populations (e.g. Africans) compared to those with small population sizes (e.g. Asians). These results imply that the substitution patterns vary significantly between populations. These findings could be explained by the effect of GC-biased gene conversion (gBGC), which favors the fixation of G/C over A/T variants in populations. In large population, gBGC causes highβ. However, in small populations, genetic drift reduces the effect of gBGC resulting in reducedβ. This was further confirmed by a positive relationship betweenNeandβfor homozygous variants. Our results highlight the huge variation in the types of homozygous and high frequency polymorphisms between world populations. We observed the same pattern for deleterious variants, implying that the homozygous polymorphisms associated with recessive genetic diseases will be more enriched with G or C in populations with largeNe(e.g. Africans) than in populations with smallNe(e.g. Europeans).
Manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics
Authors: Welch Joshua D. , Hartemink Alexander J. , Prins Jan F.
Published: April 2017

Single cell genomic techniques promise to yield key insights into the dynamic interplay between gene expression and epigenetic modification. However, the experimental difficulty of performing multiple measurements on the same cell currently limits efforts to combine multiple genomic data sets into a united picture of single cell variation. We show that it is possible to construct cell trajectories, reflecting the changes that occur in a sequential biological process, from single cell ATAC-seq, bisulfite sequencing, and ChIP-seq data. In addition, we present an approach called MATCHER that computationally circumvents the experimental difficulties inherent in performing multiple genomic measurements on a single cell by inferring correspondence between single cell transcriptomic and epigenetic measurements performed on different cells of the same type. MATCHER works by first learning a separate manifold for the trajectory of each kind of genomic data, then aligning the manifolds to infer a shared trajectory in which cells measured using different techniques are directly comparable. Using scM&T-seq data, we confirm that MATCHER accurately predicts true single cell correlations between DNA methylation and gene expression without using known cell correspondence information. We also used MATCHER to infer correlations among gene expression, chromatin accessibility, and histone modifications in single mouse embryonic stem cells. These results reveal the dynamic interplay between epigenetic changes and gene expression underlying the transition from pluripotency to differentiation priming. Our work is a first step toward a united picture of heterogeneous transcriptomic and epigenetic states in single cells.