bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of Critical Events That Lead to Spinal Cord Injury and the Importance of Rapid Reversal of Surgical Steps in Improving Neurological Outcomes
Authors: Sarwahi Vishal , Galina Jesse , Thornhill Beverly , Legatt Alan , Pawar Abhijit , Moguilevich Marina , Amaral Terry D.
Published: September 2019

Study Design.

Porcine model.

Objective.

To quantify critical vascular and mechanical events that occur before and during an evolving spinal cord injury.

Summary of Background Data.

Spinal cord injuries are one of the most devastating complications in spine surgery. Intraoperative neuromonitoring changes can occur as a secondary event of spinal cord compression and decrease in spinal cord blood flow (SCBF). Laser Doppler flowmetry has been well validated for measuring blood flow.

Methods.

Seventeen pigs were studied, 14 of which completed the experiment. Multilevel, midthoracic laminectomies were performed. Laser Doppler flowmetry electrodes were placed on the dura to measure SCBF. Spinal cord injury was induced by incremental balloon inflation in the epidural space. The animals were separated into two groups. After motor-evoked potential (MEP) loss, group A underwent medical interventions and then balloon decompression approximately 20 minutes later. Group B underwent immediate balloon decompression followed by medical interventions. After interventions, wake-up test was performed and computed tomography scan measured thoracic spinal canal volume.

Results.

Median SCBF changes were seen 15.8 (5.4–25.1) minutes before MEP loss. However, the 20% threshold interval was often reached before. At the 20% threshold, median pressure was 7 psi, balloon volume was 0.5 cm3, and 50% of the spinal canal was compromised. In group A, no pigs moved and all had pathology indicating ischemia. In group B, 9 of 10 were found to be moving their hind legs with 7 indicating ischemia.

Conclusion.

Compression spinal cord injury is the end of a cascade involving increasing intracanal pressure, decreasing canal volume, and hypoperfusion. Rapid relief of compression leads to MEP return. SCBF monitoring can detect ischemia preinjury, giving surgeons an opportunity for early intervention.

Level of Evidence: 4
Solid Organ Transplant Is Associated With Increased Morbidity and Mortality in Patients Undergoing One or Two-level Anterior Cervical Decompression and Fusion
Authors: Labaran Lawal A. , Harris Andrew B. , Puvanesarajah Varun , Amin Raj , Raad Micheal , Jain Amit , Hassanzadeh Hamid
Published: September 2019

Study Design.

Retrospective database review

Objective.

The aim of this study was to analyze the implications of solid organ transplant (SOT) on postoperative outcomes following elective one or two-level anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

Although SOTs have been associated with increased morbidity, postoperative outcomes in SOT recipients undergoing cervical spinal surgery are not well studied.

Methods.

A retrospective database review of Medicare patients younger than 85 years who underwent an elective one to two-level ACDF from 2006-2013 was conducted. Following our exclusion criteria, patients were then divided into the following groups: those with a prior history of kidney, liver, heart or lung transplant (SOT group) and non-SOT patients. Both groups were compared for hospital length of stay, 90-day major medical complications, 90-day hospital readmission, 1-year surgical site infection (SSI), 1-year revision ACDF, and 1-year mortality.

Results.

A total of 992 (0.5%) SOT recipients (1,144 organs) were identified out of 199,288 ACDF patients. SOT recipients had a significantly longer length of stay (2.32 vs. 5.22 days, p<0.001), higher rate of major medical complications (8.2% vs. 4.5%; OR 1.85, 95% CI 1.45-2.33, p<0.001) and hospital readmission (19.5% vs. 7.5%, OR 2.05, 95% CI 1.74-2.41, p<0.001). In addition, SOT patients had increased mortality within one year of surgery (5.8% vs. 1.3%; OR 3.01, 95% CI 2.26-3.94, p<0.001) compared to non-SOT patients. SOT was not independently associated with SSI (OR 1.25, 95% CI 0.85-1.75, p=0.230), and there was no significant difference in revision rate (0.9% vs. 0.5%; OR 1.54, 95% CI 0.73-2.82, p=0.202) between both groups.

Conclusion.

SOT is independently associated with longer hospital stay, increased rate of major medical complications, hospital readmission and mortality. Spine surgeons should be aware of the higher rates of morbidity and mortality in these patients and take it into consideration when developing patient-specific treatment plans.

Level of Evidence: 3
Are Outcomes of Anterior Cervical Discectomy and Fusion Influenced by Presurgical Depression Symptoms on the Mental Component Score of the Short Form-12 Survey?
Authors: Divi Srikanth N. , Goyal Dhruv K.C. , Mangan John J. , Galetta Matthew S. , Nicholson Kristen J. , Fang Taolin , Goyal Sourabh , Booth Thomas J. , Tarazona Daniel , Lucasti Christopher , Kaye I. David , Kurd Mark F. , Woods Barrett I. , Radcliff Kris E. , Rihn Jeffery A. , Anderson D. Greg , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: September 2019

Study Design.

Retrospective comparative study.

Objective.

The purpose of this study was to investigate whether preoperative depressive symptoms, measured by mental component score of the Short Form-12 survey (MCS-12), influence patient-reported outcome measurements (PROMs) following an anterior cervical discectomy and fusion (ACDF) surgery for cervical degeneration.

Summary of Background Data.

There is a paucity of literature regarding preoperative depression and PROMs following ACDF surgery for cervical degenerative disease.

Methods.

Patients who underwent an ACDF for degenerative cervical pathology were identified. A score of 45.6 on the MCS-12 was used as the threshold for depression symptoms, and patients were divided into two groups based on this value: depression (MCS-12 ≤45.6) and nondepression (MCS-12 >45.6) groups. Outcomes including Neck Disability Index (NDI), physical component score of the Short Form-12 survey (PCS-12), and Visual Analogue Scale Neck (VAS Neck), and Arm (VAS Arm) pain scores were evaluated using independent sample t test, recovery ratios, percentage of patients reaching the minimum clinically important difference, and multiple linear regression – controlling for factors such as age, sex, and BMI.

Results.

The depression group was found to have significantly worse baseline pain and disability than the nondepression group in NDI (P < 0.001), VAS Neck pain (P < 0.001), and VAS Arm pain (P < 0.001) scores. Postoperatively, both groups improved to a similar amount with surgery based on the recovery ratio analysis. The depression group continued to have worse scores than the nondepression group in NDI (P = 0.010), PCS-12 (P = 0.026), and VAS Arm pain (P = 0.001) scores. Depression was not a significant predictor of change in any PROMs based on regression analysis.

Conclusion.

Patients who presented with preoperative depression reported more pain and disability symptoms preoperatively and postoperatively; however, both groups achieved similar degrees of improvement.

Level of Evidence: 3
Validation of PROMIS CATs and PROMIS Global Health in an Interdisciplinary Pain Program for Patients With Chronic Low Back Pain
Authors: Lapin Brittany , Davin Sara , Stilphen Mary , Benzel Edward , Katzan Irene L.
Published: September 2019

Study Design.

Retrospective cohort study.

Objective.

To (1) confirm validity of Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference computer-adaptive tests (CATs) and (2) assess the validity of PROMIS Global Health (GH) and five additional PROMIS CATs: social role satisfaction, fatigue, anxiety, depression, and sleep disturbance in a population of patients with chronic low back pain (cLBP) who completed a 3-month Interdisciplinary Pain Program (IPP).

Summary of Background Data.

Recent recommendations for assessing outcomes in patients with cLBP have included PROMIS scales; however, there is a need for further evaluation, and PROMIS GH has not been studied in this population.

Methods.

The study cohort included patients with cLBP who completed the entirety of a 3-month IPP between August 2016 and December 2018. Patient-reported outcome measures (PROMs) were analyzed before the start of the IPP and at graduation. Convergent and discriminant validity were evaluated using Pearson correlation coefficients. Known groups’ validity assessed the change in PROMIS scores stratified by improvement on the Modified LBP Disability Questionnaire. Responsiveness was evaluated with standardized response means based on global impression of change.

Results.

IPP was completed by 217 patients (67.7% women, age 53.8 ± 12.8). Convergent validity was supported (P < 0.01 for all pairwise PROMs comparisons). All PROMs improved significantly by graduation, with the largest improvement for PROMIS pain interference, physical function, social role satisfaction, and Modified LBP Disability Questionnaire. Known groups’ validity demonstrated the greatest change on PROMIS physical function, social role satisfaction, pain interference, and depression. Responsiveness was supported for all PROMs in 170 (78.3%) patients who indicated at least minimal improvement (standardized response means 0.43–1.06).

Conclusion.

Our study provides support of PROMIS CATs, highlights the importance of including other meaningful outcome measures, such as social role satisfaction, and provides the first validation of PROMIS GH, in patients with cLBP. PROMs collection can be streamlined through the use of PROMIS CATs which offer advantages over legacy measures.

Level of Evidence: 3
The Effect of Parity on Age-Related Degenerative Changes in Sagittal Balance
Authors: Bailey Jeannie F. , Sparrey Carolyn J. , Williams Frances M.K. , Curran Patrick F. , Lotz Jeffrey C. , Kramer Patricia A.
Published: September 2019

Study Design.

Retrospective cohort study.

Objective.

Evaluate the effects of parity (number of births) on measures of sagittal posture in elderly women. The long-term objective of this study is to identify and mitigate factors contributing to age-related postural deformity in older adults.

Summary of Background Data.

Adult spinal deformity is a prevalent condition that often requires costly surgical management. Females are disproportionately represented in spinal deformity surgical cases with up to 90% of patients being women. The potential contributions of pregnancy on postural degeneration have only begun to be acknowledged and require further study.

Methods.

Two hundred eight women with standing lateral radiographs were selected from the TwinsUK register. Parity information was extracted from questionnaires. Sagittal balance measurements (thoracic kyphosis, lumbar lordosis [LL], pelvic incidence [PI]) were collected and PI-LL mismatch was calculated. One-way analysis of variance tests were done between three separate age categories for measures of sagittal balance and parity and stepwise multivariate regression was done for PI-LL.

Results.

Both age and PI-LL mismatch significantly differed between parity categories. PI-LL was on average 7.0° ± 2.5° greater in multiparous (3+ births) subjects than in nulliparous subjects (P < 0.01). Parity did not have an independent relationship with lumbar disc degeneration, lumbar bone mineral density, or any of the individual sagittal balance parameters (P > 0.05 for all), except for PI-LL. From a subanalysis of the effect of parity on sagittal alignment within twin pairs, we found that within pair differences in parity associate with within pair differences in thoracic kyphosis.

Conclusion.

This study established correlations between measures of spinal curvature in older women and parity for the first time. Longitudinal research is required to establish a causative relationship.

Level of Evidence: 4
Do Prophylactic Antibiotics Reach the Operative Site Adequately?
Authors: Naresh-Babu Jambuladinne , Arun-Kumar Viswanadha
Published: September 2019

Study Design.

Prospective cohort study.

Objective.

To analyze the serum and drain concentrations of antibiotics administered by two different routes and compare the results.

Summary of Background Data.

Systemic antibiotics are expected to reach the surgical site and maintain adequate concentrations of the drug to prevent infection. However, it is unknown whether systemically administered antibiotics reach and maintain such adequate concentrations at the surgical wound or not.

Methods.

Forty patients undergoing elective spine surgery received intra-wound Vancomycin (1 GM) before the wound closure and single dose of intravenous Gentamycin (80MG) immediately after surgery. Blood and drain samples were collected postoperatively to estimate serum and drain concentrations of Gentamycin and Vancomycin. Drug Estimation Protocol: Drug concentrations were estimated by ADVIA Centaur CP immunoassay (direct chemiluminescence). Gentamycin and vancomycin in the test samples competes with their respective acridinium ester-labeled gentamicin and vancomycin derivatives for monoclonal mouse anti-gentamycin and anti-vancomycin antibodies which are covalently coupled to paramagnetic particles in the solid phase.

Results.

Gentamycin attained peak serum levels at 6 hours following administration with an average value of 9.90 ± 3.1 μg/mL which was decreased to 6.76 ± 2.6 μg/mL at 12 hours and steadily declining thereafter. Even though, the drug concentrations in the drain collection from the wound also attained peak levels at 6 hours, the drug concentrations were lower (3.75 ± 1.4 μg/mL) than that of serum concentrations and inadequately attained the recommended target peak of Gentamycin (4–12 μg/mL).

Wound levels of local vancomycin were significantly higher at 6 hours (413.4 ± 217.3 μg/mL) and well maintained even at 72 hours. Serum vancomycin levels were observed to be highest at 6 hours in negligible concentrations of 6.06 ± 2.2 μg/mL.

Conclusion.

After prophylactic systemic administration of the antibiotics, the antibiotic drug concentrations in the wound are much lower than the serum concentrations at any given time. After local intra-wound application of antibiotics, the drug concentrations in the wound are well maintained even after 72 hours.

Level of Evidence: 3
How Does Ossification of Posterior Longitudinal Ligament Progress in Conservatively Managed Patients?
Authors: Park Sehan , Lee Dong-Ho , Ahn Joosuk , Cho Jae Hwan , Lee Suk Kyu , Kim Kook-Jong , Park Jae Hong , Hwang Chang Ju , Park Jae Woo , Lee Choon Sung
Published: September 2019

Study Design.

Retrospective cohort study.

Objective.

The aim of this study was to elucidate the progression of ossification of the posterior longitudinal ligament (OPLL) in conservatively managed patients and determine its risk factors

Summary of Background Data.

Although several studies have demonstrated how OPLL progresses after laminoplasty or fusion, its progression in conservatively managed patients remains unclear.

Methods.

The vertical length of the ossified mass and its thickness at each segment were evaluated on sagittal computed tomography images. Patients with vertical growth >2 mm were included in the vertical progression group. Segments with a thickness progression >1 mm were classified as thickness progressed segments, and patients who had at least one progressed segment were included in the thickness progression group. Based on the characteristics at each disc level, the ossified mass at each segment was classified into four types: type 1, no disc space involvement; type 2, involving the disc space, but not crossing; type 3, crossing the disc space, but not fused; and type 4, completely fused.

Results.

The progression of ossified mass was observed in younger patients (P < 0.01) and in C2-C3 involvement (P < 0.01) cases. Moreover, progression in both directions was observed more frequently in the mixed-type OPLL (P < 0.01). Progression occurred most often in type 3 segments (72.0%, P < 0.01). In type 3 segments, thickness progression was found more frequently in segments with segmental range of motion (ROM) ≥5° (55.6% vs. 27.8%, P = 0.04). The proportion of segments whose initial thickness was >5 mm was significantly higher among progressed segments (60.0% vs. 35.2%, P = 0.03).

Conclusion.

Young age, C2-C3 involvement, and mixed-type OPLL are risk factors for OPLL progression. Segments with morphology of crossing the segment, but without fusion (type 3), segmental ROM ≥5°, and initial thickness >5 mm need special attention.

Level of Evidence: 3
Religious Faith and Diabetes Health Beliefs in a Homeless Population
Authors: Lew Kelley Newlin , Arbuah Nancy , Nguyen Thuy
Published: September 2019

This participatory action research project explored the perspectives and challenges of homeless persons living with, or at risk for, type 2 diabetes. Because these persons were sheltered in and served by a church, their perspectives provide understanding about how religious faith may influence diabetes self-management.
Theory of Nursing for the Whole Person
Authors: Swanson Cheryl , Thompson Audrey , Valentz Rachael , Doerner Laurie , Jezek Kenda
Published: September 2019

Though unpublished in peer-reviewed literature for more than 40 years, the Theory of Nursing for the Whole Person has been, and remains, a highly useful framework for nursing practice, education, and research. Used by the College of Nursing at Oral Roberts University, the theory was developed by the founding dean, I. Tomine Tjelta. Founded on a Christian worldview, the theory is built on the basic nursing paradigm concepts, yet functions as a distinctly scriptural framework. The theory's five conceptual triads describe how nursing addresses the whole-person health-illness continuum for individuals, families, and communities.
Management of Freely Perforated Diverticulitis
Authors: Lumpkin Stephanie T. , Chaumont Nicole
Published: September 2019

CASE SUMMARY:

A healthy 65-year-old woman presents to the emergency department with a 12-hour history of sudden-onset severe lower abdominal pain. This is her first episode. She reports nausea, vomiting, and anorexia. Her last colonoscopy was at age 60, and was normal, except for diverticulosis of the sigmoid colon. Physical examination is significant for fever, tachycardia, and generalized abdominal pain with rebound tenderness. Pertinent laboratory findings include a leukocytosis and metabolic acidosis. A CT scan is obtained and is consistent with freely perforated diverticulitis, including a thickened sigmoid colon, free fluid in the pelvis, and free air noted near the diaphragm (Fig. 1). The surgeon completes the patient evaluation, recommends initiation of intravenous fluid resuscitation and antibiotics, and plans to go immediately to the operating room for surgical resection.
Distribution of Different Corneal Topography Patterns in Iranian Schoolchildren: The Shahroud Schoolchildren Eye Cohort Study
Authors: Hashemi Hassan , Pakzad Reza , Khabazkhoob Mehdi , Yekta Abbasali , Emamian Mohammad Hassan , Fotouhi Akbar
Published: September 2019

Objectives:

To determine the distribution of corneal topography patterns (CTPs) in children aged 6 to 12 years and its association with the central corneal thickness (CCT), axial length (AL), mean corneal power (MCP), and corneal astigmatism (CA).

Methods:

In this population-based study, 5,620 children selected through random stratified cluster sampling were examined. After applying the inclusion criteria, 4,655 right eyes were analyzed. The Pentacam was used to determine the CTP and measure CA and MCP, and the BioGraph was used to measure the AL. Corneal topography patterns were classified based on the 10 patterns proposed by Rabinowitz et al.

Results:

The most common pattern in the right eye was the oval pattern [32.7%, 95% confidence interval (CI): 30.9–34.5] followed by asymmetric bowtie with superior steepening (AB-SS) (14.5%, 95% CI: 13.3–15.7), whereas the rarest patterns were AB with skewed radial axis (AB-SRAX) (0.1%, 95% CI: 0.0–0.2) and irregular pattern (0.2%, 95% CI: 0.1–0.4). The similarity between the two eyes was 23.2% (95% CI: 20.9–25.7). The mean CCT was significantly higher in AB-SS than inferior steepening (IS) (P=0.023), symmetric bowtie with SRAX (SB-SRAX) (P=0.030), and AB with IS (AB-IS) (P=0.015). Corneal astigmatism was higher in SB-SRAX compared with round and oval patterns (P value for both <0.001). The AL was greater, and the MCP was lower in the oval versus the SB-SRAX pattern (P value for both <0.001).

Conclusion:

The distribution of CTP was different in children and adults, and the oval and AB-SS patterns were the most common CTPs in the current study.
Pain, Dryness, and Itch Sensations in Eye Surface Disorders Are Defined By a Balance Between Inflammation and Sensory Nerve Injury
Authors: Belmonte Carlos
Published: September 2019

Patients with corneal and conjunctival disorders report an array of ocular surface symptoms including stinging, foreign body sensation, and itching. The intensity and perceptual quality of these sensations and their duration, from brief intervals to long-term symptoms, also vary. We hypothesize that symptomatic differences across disorders reflect differences in the balance between ocular inflammation and nerve injury, with different conditions resulting from predominant effects of one of these, or a combined effect. This article provides an overview of corneal and conjunctival nerve cells, such as nociceptors and thermoreceptors, with descriptions of their morphological and molecular characteristics and their nerve-firing patterns and evoked sensations, as determined by earlier studies in animals and humans. Detailed descriptions of the changes in neuronal responses (such as abnormal responsiveness and spontaneous firing) due to local inflammation and nerve injury are provided, and assorted ocular surface disorders are discussed. Eye conditions in which inflammation is predominant include allergic conjunctivitis and photokeratitis, whereas nerve injury is the primary factor underlying complaints of dry eye after photorefractive keratectomy and in elderly patients. Both factors contribute substantially to dry eye disease and varicella-zoster infections. This model of the combined effects of inflammation and nerve injury serves to explain the different sensations reported in various eye surface disorders, including short-term versus chronic pain and dysesthesias, and may help to improve diagnoses and treatment methods.
Genomics and breast cancer screening
Authors: Tyler April L.
Published: September 2019

Many women fear the risk of developing breast cancer, and some women have increased fear because of their family history. Thankfully, the study of genetics has brought forth tools to better identify women at risk. An understanding of genetics and cancer has led to genetic testing protocols which enable at-risk women to take preventative action through medication, surgery, and intensive screenings. These protocols not only have the potential to prevent cancer but also lead to early detection. Appropriate screening for women at risk for genetic breast cancer is essential for patient care. These screenings include specific risk assessment tests, genetic counseling, and genetic testing. To provide the best possible care for patients, providers must have a basic understanding of cancer, genetics, screening tests, genetic testing, and available prevention measures.
What happens in the shock room stays in the shock room? A time-based audio/video audit framework for trauma team performance analysis
Authors: Aukstakalnis Vytautas , Dambrauskas Zilvinas , Stasaitis Kestutis , Darginavicius Linas , Dobozinskas Paulius , Jasinskas Nedas , Vaitkaitis Dinas
Published: September 2019

Introduction

A precise tool for analysis of trauma team performance is missing.

Objectives

To create a framework for trauma team performance analysis and feedback.

Methods

An observational study in a level I trauma centre in Lithuania was performed from January 1 2017 to August 31 2017. Audio/video review process was used to evaluate technical and nontechnical performance of the trauma team.

Results

In total, 143 trauma team activations were analysed. The mean rate of completion for the primary survey based on Advanced Trauma Life Support principles was 68.5%. Technical steps of patient resuscitation were measured in seconds during first hour of the treatment. The T-NOTECHS scale mean score was 11.99 (SD 2.9).

Conclusion

During the study period, we were able to measure the time needed for certain steps in trauma patient evaluation and management. Based on this analysis, a performance improvement program will be devised, including the HybridLab medical simulation, audio/video debriefing, and individualised feedback sessions.
Patient and Family Advisory Councils for Research
Authors: Harrison James D. , Anderson Wendy G. , Fagan Maureen , Robinson Edmondo , Schnipper Jeffrey , Symczak Gina , Carnie Martha B. , Hanson Catherine , Banta Jim , Chen Sherry , Duong Jonathan , Wong Celene , Auerbach Andrew D.
Published: September 2019

OBJECTIVE

To describe strategies to recruit and support members from hard-to-reach groups on research-focused Patient and Family Advisory Councils (PFACs).

BACKGROUND

Ensuring diverse representation of members of research PFACs is challenging, and few studies have given attention to addressing this problem.

METHODS

A qualitative study was conducted using 8 focus groups and 19 interviews with 80 PFAC members and leaders, hospital leaders, and researchers.

RESULTS

Recruitment recommendations were: 1) utilizing existing networks; 2) going out to the community; 3) accessing outpatient clinics; and 4) using social media. Strategies to support inclusion were: 1) culturally appropriate communication methods; 2) building a sense of community between PFAC members; 3) equalizing roles between community members/leaders; 4) having a diverse PFAC leadership team; and 5) setting transparent expectations for PFAC membership.

CONCLUSION

Increasing the diversity of research PFACs is a priority, and it is important to determine how best to engage groups that have been traditionally underrepresented.
Optimizing Perioperative Pain Control After Ambulatory Urogynecologic Surgery
Authors: Winkelman William D. , Kim Youngwu , Erlinger Adrienne L. , Haviland Miriam J. , Hacker Michele R. , Elkadry Eman A.
Published: September 2019

Objectives

The objective of this study was to determine the impact of a multimodal protocol on opiate use and postoperative pain after ambulatory urogynecologic surgery.

Methods

This was a retrospective cohort study comparing ambulatory urogynecologic surgery patients treated under a standard perioperative pain protocol with those treated under a multimodal perioperative pain protocol. The multimodal protocol consisted of preoperative gabapentin and acetaminophen and postoperative scheduled doses of acetaminophen and nonsteroidal anti-inflammatory drugs. Pain scores were obtained from nursing records and assessed on the Numeric Rating Scale 11 per hospital protocol. All opioid dosages were converted into morphine milligram equivalents using standardized conversion tables.

Results

We treated 109 patients under the standard protocol and 112 under the multimodal protocol. Patients had similar baseline characteristics. Overall, a minority of patients (39%) used postoperative opioids; this was similar in the 2 groups (P=0.45). The 2 groups also were similar with regard to the total postoperative morphine milligram equivalents (P=0.35). Postoperatively, patients treated under the standard protocol had higher mean pain scores (2.2 vs 1.4, P=0.002). Patients treated under the standard protocol were also significantly more likely to report postoperative pain (69%) than those treated under the multimodal protocol (52%; P=0.01), and the multimodal protocol was associated with a 25% lower risk of postoperative pain (risk ratio, 0.75; 95% confidence interval, 0.60–0.94) than the standard protocol.

Conclusions

Patients infrequently use opiates after ambulatory urogynecologic surgery. The use of a multimodal pain protocol was associated with lower pain scores, and patients in a multimodal pain protocol were more likely to report no pain.
A Clinical Risk Model to Predict Obstetric Anal Sphincter Injuries in Laboring Patients
Authors: Woo Victoria G. , Hung Yun-Yi , Ritterman-Weintraub Miranda L. , Painter Caitlyn E. , Ramm Olga
Published: September 2019

Objective

Our objective was to develop a risk stratification tool for predicting obstetric anal sphincter injury risk in women during labor.

Methods

In this retrospective cohort study of singleton deliveries within Kaiser Permanente Northern California, a predictive model for anal sphincter injury was developed within the 2013 birth cohort and validated in the 2014 birth cohort of 22,741 births. Predictors of obstetric anal sphincter injury were identified using multiple regression analysis and used to create a risk calculator tool based on effect size and clinical judgment.

Results

Duration of second stage of labor, vacuum delivery, history of anal sphincter injury, maternal and gestational ages, and maternal race and ethnicity were associated with elevated risk of anal sphincter injury. Using these risk factors, we developed a validated parity-stratified scoring system. Among nulliparous women, 116 (1.3%) had a score of zero, corresponding to a 0.9% risk, and 1024 (11.7%) had a score higher than 6, corresponding to a 27.5% risk of anal sphincter injury. Among the multiparous women, 1181 (8.4%) had a score of zero, corresponding to a 0.1% risk, and the 260 (1.9%) with a score higher than 10 had a 7.7% risk. The predictive ability of the score derived based on the 2013 data was applied to the 2014 data, and results showed that the predictive abilities were statistically similar, except for one subgroup: multiparous women with a total score of ≥10.

Conclusions

Our anal sphincter injury risk stratification tool effectively predicts individual risk and can inform clinician and patient decision making to minimize maternal birth trauma.
Independent Activity Subspaces for Working Memory and Motor Preparation in the Lateral Prefrontal Cortex
Authors: Tang Cheng , Herikstad Roger , Parthasarathy Aishwarya , Libedinsky Camilo , Yen Shih-Cheng
Published: September 2019

The lateral prefrontal cortex is involved in the integration of multiple types of information, including working memory and motor preparation. However, it is not known how downstream regions can extract one type of information without interference from the others present in the network. Here we show that the lateral prefrontal cortex contains two independent low-dimensional subspaces: one that encodes working memory information, and another that encodes motor preparation information. These subspaces capture all the information about the target in the delay periods, and the information in both subspaces is reduced in error trials. A single population of neurons with mixed selectivity forms both subspaces, but the information is kept largely independent from each other. A bump attractor model with divisive normalization replicates the properties of the neural data. These results have implications for the neural mechanisms of cognitive flexibility and capacity limitations.
Kin discrimination promotes horizontal gene transfer between unrelated strains inBacillus subtilis
Authors: Stefanic Polonca , Belcijan Katarina , Kraigher Barbara , Kostanjšek Rok , Nesme Joseph , Madsen Jonas , Kovac Jasna , Sørensen Søren , Vos Michiel , Mandic-Mulec Ines
Published: September 2019

B. subtilisis a surface-dwelling bacterium that is competent for natural transformation. Genetically distinctB. subtilisswarms form a boundary upon encounter, mediated by a fast-evolving molecular kin discrimination (KD) system. We here demonstrate that KD-mediated swarm antagonisms inB. subtilispromote transformation-mediated horizontal gene transfer between strains of low relatedness. Gene transfer is largely uni-directional and the result of the induction of competence of the recipient strain by the donor strain is linked to a sigW-mediated stress response. More closely related strains, which in theory would experience more efficient recombination due to increased sequence homology, did not upregulate transformation upon encounter, demonstrating that social interactions can override mechanistic barriers to horizontal gene transfer. KD-mediated competence in response to the encounter of distinct neighbouring strains could maximize the probability of efficient incorporation of novel alleles and genes that have proved to function in a genomically and ecologically similar context.
Plasticity in medaka gonadotropes via cell proliferation and phenotypic conversion
Authors: Fontaine Romain , Ager-Wick Eirill , Hodne Kjetil , Weltzien Finn-Arne
Published: September 2019

Follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) produced by the gonadotropes, play a major role in control of reproduction. Contrary to mammals and birds, Lh and Fsh are mostly produced by two separate cell types in teleost. Here, we investigated gonadotrope plasticity, using transgenic lines of medaka (Oryzias latipes) where DsRed2 and hrGfpII are under the control of fshb and lhb promotors respectively. We found that Fsh cells first appear in the pituitary at 8 dpf. Similar to in Lh cells, Fsh cells show hyperplasia from juvenile to adult stages. Hyperplasia is stimulated by estradiol exposure. Both Fsh and Lh cells show hypertrophy during puberty with similar morphology. They also share similar behavior, using their cellular extensions to make networks. We observed bi-hormonal gonadotropes in juvenile and adult fish but not during larval stage where only mono-hormonal cells are observed, suggesting the existence of phenotypic conversion between Fsh and Lh in later stages. This is demonstrated in cell culture, where some Fsh start to producelhb, a phenomenon enhanced by gonadotropin releasing hormone (Gnrh) stimulation. We have previously shown that medaka Fsh cells lack Gnrh receptors, but here we show that with time in culture, some Fsh cells start responding to Gnrh, whilefshbmRNA levels are significantly reduced, both suggestive of phenotypic change. All together, these results reveal high plasticity of gonadotropes due to both estradiol sensitive proliferation and Gnrh promoted phenotypic conversion, and also shows that gonadotropes lose part of their identity when kept in cell culture.
Immunoinformatic and dynamic simulation-based designing of a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis
Authors: Nain Zulkar , Abdullah Faruq , Rahman M. Mizanur , Karim Mohammad Minnatul , Rahman S. M. Raihan , Khan Shakil Ahmed , Sayed Sifat Bin , Sheam Md. Moinuddin , Haque Zahurul , Adhikari Utpal Kumar
Published: September 2019

Elizabethkingia anophelis is an emerging human pathogen causing neonatal meningitis, catheter-associated infections and nosocomial outbreaks with high mortality rates. Besides, they are resistant to most antibiotics used in empirical therapy. In this study, therefore, we used immunoinformatic approaches to design an epitope-based vaccine against E. anophelis as an alternative preventive measure. Initially, T-cell (CTL and HTL) and B-cell (LBL) epitopes were predicted from the highest antigenic protein. The CTL and HTL epitopes together had a population coverage of 99.97% around the world. Eventually, 6 CTL, 7 HTL, and 2 LBL epitopes were selected and used to construct a multiepitope vaccine. The vaccine protein was found to be highly immunogenic, non-allergenic, and non-toxic. Codon adaptation and in silico cloning were performed to ensure better expression within E. coli K12 host system. The stability of the vaccine structure was also improved by disulphide bridging. In addition, molecular docking and dynamic simulation revealed good and stable binding affinity between the vaccine and receptor. The immune simulation showed higher levels of T-cell and B-cell activities which was in coherence with actual immune response. Repeated exposure simulation resulted in higher clonal selection and faster antigen clearance. Nevertheless, experimental validation is required to ensure the immunogenic potency and safety of this vaccine to control E. anophelis infection in the future.
Genotyping complex structural variation at the malaria-associated human glycophorin locus using a PCR-based strategy
Authors: Algady Walid , Weyell Eleanor , Mateja Daria , Garcia André , Courtin David , Hollox Edward J
Published: September 2019

Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically-significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants and accurate genotyping of this complex structural variation remains a challenge. Here, we use a PCR-based strategy to genotype structural variation at the human glycophorin gene cluster. We validate our approach, based on a triplex paralogue ratio test (PRT) combined with junction-fragment specific PCR, on publically-available samples from the 1000 Genomes project. We then genotype a longitudinal birth cohort using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment.
Deep Learning-Based Analysis of Macaque Corneal Sub-Basal Nerve Fibers in Confocal Microscopy Images
Authors: Oakley Jonathan D. , Russakoff Daniel B. , McCarron Megan E. , Weinberg Rachel L. , Izzi Jessica M. , Mankowski Joseph L.
Published: September 2019

Purpose

To describe and assess different deep learning-based methods for automated measurement of macaque corneal sub-basal nerves using in vivo confocal microscopy (IVCM).

Methods

The automated assessment of corneal nerve fiber length (CNFL) in IVCM images is of increasing clinical interest. These measurements are important biomarkers in a number of diseases including diabetes mellitus, human immunodeficiency virus, Parkinson’s disease and multiple sclerosis. Animal models of these and other diseases play an important role in understanding the disease processes as efforts toward developing new and effective therapeutics are made. And while automated methods exist for nerve fiber analysis in clinical data, differences in anatomy and image quality make the macaque data more challenging and has motivated the work reported here.

Toward this goal, nerves in macaque corneal IVCM images were manually labelled using an ImageJ plugin (NeuronJ). Different deep convolutional neural network (CNN) architectures were evaluated for accuracy relative to the ground truth manual tracings. The best performing model was used on separately acquired macaque ICVM images to additionally compare inter-reader variability.

Conclusions

Deep learning-based segmentation of sub-basal nerves in IVCM images shows excellent correlation to manual segmentations in macaque data. The technique is indistinguishable across readers and paves the way for more widespread adoption of objective automated analysis of sub-basal nerves in IVCM.

Translational Relevance

Quantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management. This work reports on different approaches that, in using deep learning-based techniques, leverage state of the art analysis methods to demonstrate performance akin to human graders. In application, the approach is robust, rapid and objective, offering utility to a variety of clinical studies using IVCM.
Homo-Oligomerisation in Signal Transduction: Dynamics, Homeostasis, Ultrasensitivity, Bistability
Authors: Koch Daniel
Published: September 2019

Homo-oligomerisation of proteins is a ubiquitous phenomenon whose exact role remains unclear in many cases. To identify novel functions, this paper provides an exploration of general dynamical mathematical models of homo-oligomerisation. Simulation and analysis of these models show that homo-oligomerisation on its own allows for a remarkable variety of complex dynamic and steady-state regulatory behaviour such as transient overshoots or homeostatic control of monomer concentration. If post-translational modifications are considered, however, conventional mass-action kinetics leads to thermodynamic inconsistencies due to asymmetric combinatorial expansion of reaction routes. Introducing a conservation principle to balance rate equations re-establishes thermodynamic consistency. Using such balanced models it is shown that oligomerisation can lead to bistability by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby constituting a novel motif for bistable modification reactions. Due to these potential signal processing capabilities, homo-oligomerisation could play far more versatile roles in signal transduction than previously appreciated.
Anti-angiogenic activities of the leaves of Tapinanthus bangwensis (Engl. and K. Krause) Danser Loranthaceae growing on three host trees in south-western Nigeria
Authors: Diyaolu Oluwatofunmilayo Arike , Attah Alfred Francis , Adeagbo AS , Fukushi Y , Moody Jones Olanrewaju
Published: September 2019

The control of angiogenic process is of immense importance to the overall health of mankind to avert out-of-control complications such as tumours and cancers. Tapinanthus bangwensis (TBG) is a semi-parasitic plant with multipurpose uses in Nigerian ethno-medicine among which is its anti-infective properties as well as the anti-tumor and restoration of damaged tissues. Despite the wide and varied uses of TBG, the anti-angiogenic investigation of the plant on different host trees is lacking while the documentation and scientific validation of indigenous knowledge on plants’ use is urgent. The present work focuses on the anti-angiogenic activities of the crude extracts and partitioned fractions of the leaves of Tapinanthus bangwensis (TBG) using the Chick chorio allantoic membrane (CAM) model. The plant was collected from three different host trees namely Albizia lebbeck (AL), Stereospermum kunthianum (SK) and Tabebuia rosea (TR). The methanolic crude extracts and solvent-partitioned fractions of TBG-SK samples were assessed for their anti-angiogenic activities using the chick chorio allantoic membrane (CAM) in ovo and in vitro assay methods respectively. Purification and isolation of major compound(s) in the chloroform fraction of TBG extract obtained from Stereospermum kunthianum host tree (TBG-SK) was carried out using chromatographic and spectroscopic methods (NMR, MS).

The crude methanolic extract of TBG-SK was most potent (100% activity) in the CAM in ovo assay while the chloroform fraction produced a significantly (p<0.05) highest average reduction in blood vessels with resultant formation of large avascular zones on CAM following an in vitro CAM assay. The anti-angiogenic chloroform fraction revealed the presence of a UV-active triterpenoid moiety. Findings from this work, has provided some justification for the folkloric use of TBG and thus forms a potential basis for drug discovery for wide-ranging disease states.
Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer
Authors: Cubillos-Angulo Juan M. , Fukutani Eduardo R. , Cruz Luís A. B. , Arriaga María B. , Lima João Victor , Andrade Bruno B. , Queiroz Artur T. L. , Fukutani Kiyoshi F.
Published: September 2019

Background

Cigarette smoking is associated with increased risk of developing respiratory diseases and various types of cancer. Early identification of such unfavorable outcomes in patients who smoke is critical for optimizing personalized medical care.

Methods

Here, we perform a comprehensive analysis using Systems Biology tools of publicly available data from a total of six transcriptomic studies, which examined different specimens of lung tissue and/or cells of smokers and nonsmokers to identify potential markers associated with lung cancer.

Results

Expression level of twenty-two genes was capable of classifying smokers from non-smokers. A machine learning algorithm revealed that AKR1B10 was the most informative gene among the 22 DEGs accounting for the classification of the clinical groups. AKR1B10 expression was higher in smokers compared to non-smokers in datasets examining small and large airway epithelia, but not in the data from a study of sorted alveolar macrophages. We next tested whether AKR1B10 expression could be useful in identification of cancer tissue in patients who were not exposed to smoking. AKR1B10 expression was substantially higher in lung cancer specimens compared to matched healthy tissue obtained from nonsmoking individuals (accuracy: 80%, p<0.0001). Finally, we searched the expression of 11 single nucleotide polymorphisms (SNPs) of AKR1B10 worldwide. We found that the SNP rs782881 was the most frequent mutant allele in the majority of continents. Africa was the continent which exhibited higher frequency of SNPs associated with lower AKR1B10 expression and displayed lower lung cancer incidence and deaths attributable to tobacco.

Conclusion

The systematic analysis of transcriptomic studies performed here revealed a potential critical link between AKR1B10 expression, smoking and occurrence of lung cancer.
Effects of Transcranial Direct Current Stimulation on GABA and Glutamate in Children: A Pilot Study
Authors: Nwaroh C , Giuffre A , Cole L , Bell T , Carlson H. L. , MacMaster F. P. , Kirton A , Harris AD
Published: September 2019

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS) it has been shown that tDCS can affect local levels of γ-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right handed children ages 12–18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glutamate and GABA were measured before and after the protocol (at day 5 and 6 weeks) using conventional MRS and GABA-edited MRS in the sensorimotor cortices. Glutamate measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and glutamate in the developing brain and therefore it may demonstrate different responses in adults.