bluuebunny/crossref_metadata_2025 huggingface dataset:
CARE Scale-7
Authors: Ziadni Maisa , You Dokyoung S. , Wilson Anna C. , Darnall Beth D.
Published: March 2018

Objectives:

Social and interpersonal factors may impact chronic pain self-care and self-management; however, no integrated measure exists to assess the interplay of these factors. We developed and tested a measure designed to assess salient interpersonal factors, including relationship guilt and worry, and difficulty prioritizing self-care in chronic pain.

Methods:

We tested self-report items broadly relevant to locus of care, limit-setting capacity, and worry/guilt about relationships in 3 discrete chronic pain samples (total N=1,452): (1) online sample of chronic pain clinic patients (N=729; 21 candidate CARE items, sociodemographics, and measures of psychological and physical functioning). Analytic results supported a final 7-item CARE scale that was next tested in (2) an anonymous online sample of 578 adults with chronic pain. (3) Finally, preliminary validation of the CARE scale was performed in a tertiary pain clinic sample (N=145).

Results:

Exploratory factor analysis revealed a 7-item, 2-factor solution (difficulty prioritizing self-care and guilt/worry) that accounted for a combined total of 58% of the variance. CARE scale-7 had modest convergent validity with pain intensity, pain-related interference, and emotional distress. Extreme difficulty with both factors was reported by about one-third of the total sample, suggesting that relationship factors significantly impact pain management and self-care.

Discussion:

Social factors are gaining attention for their influence on the trajectory of chronic pain. The CARE scale is a brief, integrated measure that may be used to reveal specific interpersonal and personal impediments to self-care, and identify important therapeutic targets to optimize self-management behaviors.
In Vitro Negative Inotropic Effect of Low Concentrations of Bupivacaine Relates to Diminished Ca2+ Sensitivity but Not to Ca2+ Handling or β-Adrenoceptor Signaling
Authors: Flenner Frederik , Arlt Nicole , Nasib Mahtab , Schobesberger Sophie , Koch Thea , Ravens Ursula , Friedrich Felix , Nikolaev Viacheslav , Christ Torsten , Stehr Sebastian N.
Published: March 2018

Background

Systemic toxicity of local anesthetics is predominantly complicated by their myocardial toxicity. Especially long-acting local anesthetics exert a negative inotropic effect that has been described at lower concentrations than defined for blockade of myocardial ion channels. We evaluated the negative inotropic effect of bupivacaine at a concentration described for clinical toxicity testing the hypothesis that negative inotropy is a result of reduced Ca2+ sensitivity rather than blockade of ion channels.

Methods

We simultaneously measured force development and action potentials in guinea pig right papillary muscles (n = 5 to 7). L-type Ca2+ currents (n = 8 to 16) and Ca2+ transients (n = 10 to 11) were measured in isolated cardiomyocytes. Sensitivity of myofilaments to Ca2+ was assessed in skinned fibers (n = 10). Potential effects of bupivacaine on 3′,5′-cyclic adenosine monophosphate concentrations were measured using Förster Resonance Energy Transfer (n = 12 to 14) microscopy.

Results

Bupivacaine reduced force in a concentration-dependent manner from 173 ± 119 µN at baseline to 28 ± 13 µN at 300 µM (mean ± SD). At concentrations giving half-maximum negative inotropic effects (5 µM), the maximum upstroke velocity of action potentials, as a surrogate of sodium channel activity, was unaffected. Maximum positive inotropic effects of isoprenaline were also reduced to 50%. Neither basal nor isoprenaline-induced 3′,5′-cyclic adenosine monophosphate accumulation, L-type Ca2+ currents, or Ca2+ transients were affected by 5 µM bupivacaine, but this concentration significantly decreased Ca2+ sensitivity of myofilaments, changing the negative logarithm of the half-maximum effective Ca2+ concentrations from 5.66 to 5.56 –log[M].

Conclusions

We provide evidence that the negative inotropic effect of bupivacaine may be caused mainly by a reduction in myofilament sensitivity to Ca2+.
Biological Rationale for the Use of Vertebral Whole Bone Marrow in Spinal Surgery
Authors: Salamanna Francesca , Cepollaro Simona , Contartese Deyanira , Giavaresi Gianluca , Brodano Giovanni Barbanti , Griffoni Cristiana , Gasbarrini Alessandro , Fini Milena
Published: March 2018

Study Design.

Laboratory study.

Objective.

Mesenchymal stem cells (MSCs) derived from whole bone marrow aspirate (BMA) and MSCs derived from density-gradient centrifugation were isolated from vertebral bodies and cultured under either hypoxic or normoxic conditions to evaluate their biological characteristics and HOX and TALE signature able to improve spinal surgery procedures.

Summary of Background Data.

The use of spinal fusion procedures has increased over the last decades; however, failed fusion still remains an important problem. Clinician and researchers focused their attention on the therapeutic potential of bone marrow MSCs and several methods for their isolation and cultivation have been developed. However, the best source and techniques are still debated.

Methods.

MSCs morphology, surface markers, colony-forming-units, and three lineage differentiation through quantitative real-time PCR (qPCR) were evaluated. Additionally, gene expression analysis of HOX and TALE signatures during osteogenic differentiation were analyzed.

Results.

Our study showed that MSCs derived from whole BMA were successfully isolated and when cultured under hypoxic condition presented greater proliferation, larger colonies, and differentiated onto osteogenic and chondrogenic lineage with greater ability, while adipogenic differentiation was less efficient. Results also revealed that MSCs, differently isolated and cultured, expressed different level of HOX and TALE signatures and that HOXB8 were up-regulated with greater efficiency in MSCs derived from whole BMA under hypoxia.

Conclusion.

Our data indicated that hypoxic preconditioning of MSCs derived from whole BMA exhibited more suitable biological characteristics and different level of HOX and TALE gene activation. We, therefore, concluded that vertebral body MSCs derived from whole BMA may provide alternative sources of MSCs for tissue engineering applications for spine surgery.

Level of Evidence: N/A
Gravidity, Parity, and Vertebral Dimensions in the Northern Finland Birth Cohort 1966
Authors: Oura Petteri , Paananen Markus , Auvinen Juha , Niinimäki Jaakko , Niinimäki Maarit , Karppinen Jaro , Junno Juho-Antti
Published: March 2018

Study Design.

A population-based birth cohort study.

Objective.

To investigate the association between gravidity, parity, and vertebral geometry among middle-aged women.

Summary of Background Data.

Vertebral size is a recognized determinant of vertebral fracture risk. Yet, only a few lifestyle factors that influence vertebral size are known. Pregnancy is a labile period that may affect the maternal vertebral size or shape. The lumbar lordosis angle is permanently deepened by pregnancy, but it remains unclear whether vertebral shape or size contribute to this deepened angle.

Methods.

We aimed to investigate whether gravidity and parity were associated with vertebral cross-sectional area (CSA) and height ratio (anterior height to posterior height) among 705 middle-aged women from the Northern Finland Birth Cohort 1966. We measured the corpus of their fourth lumbar vertebra using magnetic resonance imaging of the lumbar spine at the age of 46. Gravidity and parity were elicited using a questionnaire also at the age of 46. Linear regression analysis was used with adjustments for body mass index, vertebral CSA (height ratio models), and vertebral height (CSA models). We also ran a subgroup analysis that did not include nulliparous women, and we compared nulliparous women with grand multiparous women.

Results.

The models found no statistically significant associations between the predictors and outcomes. Crude and adjusted results were highly similar, and the subgroup analyses provided analogous results.

Conclusion.

Pregnancy, or even multiple pregnancies, do not seem to have long-term effects on vertebral geometry. In order to enhance the prevention of vertebral fractures, future studies should aim to reveal more lifestyle determinants of vertebral size.

Level of Evidence: 3
Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma
Authors: Baumann Brian C. , Wei Jenny , Plastaras John P. , Lukens John N. , Damjanov Nevena , Hoteit Maarouf , Hsu Christine , Levine Matthew , Mondschein Jeffrey , Nadolski Gregory , Olthoff Kim , Reiss Kim A. , Rosen Mark , Siegelman Evan , Metz James M. , Ben-Josef Edgar
Published: March 2018

Objectives:

Stereotactic body radiotherapy (SBRT) is potentially curative treatment for small hepatocellular carcinomas (HCC), but data are limited on its efficacy and toxicity. We hypothesized that SBRT can achieve excellent local control (LC) with acceptable toxicity treating HCC lesions, even in advanced cirrhosis.

Materials and Methods:

Thirty-seven nonmetastatic HCC patients received SBRT to 43 lesions between October 2012 and April 2016. Median dose was 50 Gy/5 fractions. All Child-Pugh (CP) ≥B patients underwent a planned 1-month break after the first 3 fractions to assess hepatic toxicity. Patients were treated without separately placed fiducial markers using Linac-based SBRT with breath-hold (67%) or 4D-computed tomography with compression belt (33%) to reduce motion. Patients underwent magnetic resonance imaging q3 months post-SBRT.

Results:

Median age was 65 (range, 44 to 88). Pre-SBRT mean CP was 6.4 (range, A5 to C11). Nine (24%) had CP≥B8. Thirty-one of 33 patients (93%) had prior liver-directed therapy (median 2). Seventeen (40%) had solitary lesions. Median lesion diameter was 2.7 cm (range, 1.1 to 5.6). Median follow-up was 14 months (range, 2 to 45). There was 1 local failure (multifocal HCC with 3 prior transarterial chemoembolization). LC, freedom from liver progression, and overall survival at 12 months was 95%, 66%, 87% in the full cohort, and 100%, 76%, 93% for patients with solitary lesions. Four had grade 3 toxicity (ascites [n=2]/gastrointestinal bleed [n=1]/capsular pain [n=1]). Eight of 9 CP≥B8 patients had no grade ≥3 hepatic toxicity.

Conclusions:

SBRT for HCC is well-tolerated even in patients with advanced cirrhosis and prior liver-directed treatment and provides excellent LC even for larger lesions that cannot be controlled with radiofrequency ablation. LC with SBRT compares favorably to other liver-directed therapies. Prospective studies comparing SBRT with other liver-directed therapies are warranted.
CYP2C19 Genotype is an Independent Predictor of Adverse Cardiovascular Outcome in Iraqi Patients on Clopidogrel After Percutaneous Coronary Intervention
Authors: Mohammad Ameen M. , Al-Allawi Nasir A. S.
Published: March 2018

To determine the impact of CYP2C19 genotyping on the occurrence of major adverse cardiovascular events (MACE), in cohort of Iraqi patients on clopidogrel after percutaneous coronary intervention (PCI), a total of 201 Iraqi patients undergoing the latter procedure were enrolled. All enrollees had their CYP2C19 genotyped using polymerase chain reaction and reverse hybridization. Genotyping revealed that CYP2C19 *1, *17, *2, and *8 allele frequencies were, respectively, 0.604, 0.276, 0.117, and 0.0026. After the exclusion of those with 2 loss of function alleles, 186 patients were available for follow-up as long as they were on clopidogrel, or until MACE occurred, which was encountered in 8.6% after a median of 12 months. Among predictors associated with MACE was the carriage of one CYP2C19 loss of function allele {hazard ratio (HR) 8.6 [confidence interval (CI) 3.15–23.4]; P < 0.0005}, hypertension [HR 3.74 (CI 1.06–13.16); P = 0.04], reduced ventricular function [HR 3.88 (1.43–10.54); P = 0.008], and history of previous myocardial infarction [HR 4.9 (CI 1.48–11.33); P = 0.007] by univariate analysis, although only CYP2C19 genotype remained significant by multivariate analysis [HR 11.88 (CI 3.25–43.44); P < 0.0005]. The latter observation favors CYP2C19 genotype–guided antiplatelet therapy and extending the use of alternative antiplatelet drugs to those with single loss of function allele after percutaneous coronary intervention.
A Systematic Review of Integrated Care Interventions Addressing Perinatal Depression Care in Ambulatory Obstetric Care Settings
Authors: MOORE SIMAS TIFFANY A. , FLYNN MICHAEL P. , KROLL-DESROSIERS AIMEE R. , CARVALHO STEPHANIE M. , LEVIN LEONARD L. , BIEBEL KATHLEEN , BYATT NANCY
Published: March 2018

This systematic review searched 4 databases (PubMed/MEDLINE, Scopus, CINAHL, and PsychINFO) and identified 21 articles eligible to evaluate the extent to which interventions that integrate depression care into outpatient obstetric practice are feasible, effective, acceptable, and sustainable. Despite limitations among the available studies including marked heterogeneity, there is evidence supporting feasibility, effectiveness, and acceptability. In general, this is an emerging field with promise that requires additional research. Critical to its real-world success will be consideration for practice workflow and logistics, and sustainability through novel reimbursement mechanisms.
ASYMMETRIC DIABETIC RETINOPATHY PROGRESSION IN PATIENTS WITH AXIAL ANISOMETROPIA
Authors: Kim Dong Yoon , Song Ji Ho , Kim Yoon Jeon , Lee Joo Yong , Kim June-Gone , Yoon Young Hee , Joe Soo Geun
Published: March 2018

Purpose:

To investigate the differences in the progression of diabetic retinopathy (DR) in both eyes of patients with axial anisometropia.

Methods:

A retrospective review was conducted on diabetic patients who had different axial lengths (difference greater than 1 mm) in each eye. The primary objective of this study was to analyze the differences in the progression of DR in both eyes of patients with axial anisometropia. Fundus images (fluorescein angiography and photographs of the fundus covering the Early Treatment Diabetic Retinopathy Study seven fields) were graded using the Early Treatment Diabetic Retinopathy Study DR grading system. Also, the severity of diabetic retinopathy was analyzed based on the axial length and subfoveal choroidal thickness.

Results:

Thirty-four of 6,963 patients with DR were included after applying the exclusion and inclusion criteria. The mean age was 53.53 ± 12.20 years and duration of diabetes was 9.63 ± 7.73 years. The mean axial length of the longer and shorter eye was 26.21 ± 2.04 mm and 23.21 ± 1.73 mm, respectively (P < 0.001). In shorter eyes, 61.7% (21 of 34) of the eyes had proliferative diabetic retinopathy. In contrast to the shorter eye, only 8 of the longer eyes (8 of 34, 23.5%) had proliferative diabetic retinopathy (McNemar test, P < 0.001). In eyes with thin subfoveal choroidal thickness (<250 µm), the proliferative diabetic retinopathy ratio was significantly lower (P = 0.007).

Conclusion:

In patients with axial anisometropia, the longer eye had a lower degree of DR progression than the shorter eye. This result showed that elongation of the axial length had a protective effect against the progression of DR without individual confounding factors.
RETINAL MICROSTRUCTURE IN POEMS SYNDROME
Authors: Tomita Ryutaro , Sekiryu Tetsuju , Shintake Hiroaki , Saito Kuniharu
Published: March 2018

Purpose:

To report a 67-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, showing bilateral serous retinal detachment. The retinal lesion was evaluated by multimodal imaging using spectral domain optical coherence tomography and an adaptive optics (AO) camera.

Methods:

A case report.

Results:

Optical coherence tomography showed hyperreflective foci mainly in the inner retina in both eyes. The AO images showed many low-reflective dots in the right eye. Three months after hematological treatment, both hyperreflective foci in the optical coherence tomography images and the low-reflective dots in the AO images disappeared.

Conclusion:

Low-reflective dots were detected in AO images of eyes with serous retinal detachment secondary to POEMS syndrome. AO cameras can detect retinal microstructures in living eyes.
A Simple Quantitative Measure of Orbital Compliance
Authors: Dunbar Kristen E. , Abascal Cristina , Pandit Saagar A. , Kazim Michael
Published: March 2018

Purpose:

This study evaluates the reliability of a frequently used subjective measurement of orbital compliance (0–3 scale) and describes a simple, quantitative measure with excellent intra- and interrater reliability.

Methods:

Two examiners performed both measurements on 100 orbits (50 consecutive patients) from the office of 1 oculoplastics surgeon. Each measurement was obtained at 2 different time points, 10 minutes apart. For the subjective measurement, the patient was asked to close their eyes, and the globe was displaced posteriorly with digital pressure until moderate resistance was felt. This was graded on a 0 to 3 scale. For the quantitative measurement (millimeter scale), the difference in axial displacement was measured using a Hertel exophthalmometer.

Results:

The subjective measurement (scale, 0–3) showed excellent test–retest reliability (average, 0.901) for both examiners at both time points and good interobserver reliability (average, 0.677). The quantitative measurement (millimeter scale) showed excellent test–retest reliability (average, 0.848) and very good interobserver reliability (average, 0.756).

Conclusion:

This study shows that while both methods have both excellent test–retest reliability, the interobserver reliability is slightly higher with the quantitative measurement. This suggests that the described measurement of orbital compliance is both a reasonable alternative and possibly more accurate measurement without the steep learning curve.
Quantitative Assessment of Dry Eye Parameters After Müller’s Muscle-Conjunctival Resection
Authors: Bautista Sana Ali , Wladis Edward J. , Schultze Robert L.
Published: March 2018

Purpose:

Müller’s muscle-conjunctival resection (MMCR) is a highly effective technique to correct upper eyelid ptosis. However, several authorities have raised concerns about the possibility of postoperative ocular surface dryness. This study was performed to assess the impact of MMCR on clinically meaningful parameters of the ocular surface.

Methods:

In adult patients, tear break-up time, lipid layer thickness, and osmolarity were measured via direct observation, interferometry, and impedance measurements before surgery and 3 months after surgery in patients who underwent MMCR. Statistical analysis was performed via a dedicated software package.

Results:

Fifteen eyes of 14 patients were included in the study. Mean pre- and postoperative tear break-up times were 12.71 ± 2.20 and 12.43 ± 2.41 seconds, respectively (p = 0.1648). Preoperatively, the mean lipid layer thickness measurement was 91.00 ± 7.02 nm, whereas the mean postoperative value was 88.86 ± 21.36 nm (p = 0.6613). The mean preoperative tear osmolarity measured 291.4 ± 8.86 mOsm/l, and the mean postoperative measurement was 289.86 ± 9.74 mOsm/l (p = 0.2652).

Conclusions:

MMCR does not appear to change clinically meaningful ocular surface disease parameters, and postoperative dryness did not result from this procedure. In appropriately selected patients, MMCR can be safely performed without increased concerns regarding postoperative dry eye disease.
Orbital and Ocular Ischemic Syndrome With Blindness After Facial Filler Injection
Authors: Ramesh Sathyadeepak , Fiaschetti Danica , Goldberg Robert A
Published: March 2018

The authors herein describe a case of orbital and ocular ischemic syndrome with blindness after cosmetic hyaluronic acid filler injection. Orbital function, but not visual function, returned after treatment with orbital hyaluronidase and corticosteroids.
Telmisartan Improves Insulin Resistance: A Meta-Analysis
Authors: Wang Yan , Qiao Shun , Han De-Wu , Rong Xin-Ren , Wang Yi-Xiao , Xue Jing-jing , Yang Jing
Published: March 2018

Background:

Diabetes mellitus, metabolic syndrome, and other obesity-related diseases are characterized by insulin resistance (IR) as a common pathophysiological change and are closely related to cardiovascular disease, which seriously threaten human health. Telmisartan belongs to a group of drugs called angiotensin II receptor antagonists (ARBs) and it can partially activate peroxisome proliferator–activated receptors. Animal experiments have confirmed that telmisartan can regulate glucose and lipid metabolism, and improve IR.

Study Question:

This study performs a systematic review of the advantages of telmisartan in improving IR and compared it with other ARBs.

Study Design:

Randomized controlled trials (RCTs) that compared telmisartan with other ARBs in patients with obesity, diabetes, impaired glucose tolerance, and metabolic syndrome were searched from PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, and Chinese biomedical literature database (CBM). RCTs published as of the end of April 2017 were included in the present study.

Measures and Outcomes:

The outcomes included homeostasis model assessment of insulin resistance, fasting blood glucose level, fasting insulin level, diastolic blood pressure, and systolic blood pressure. We used a fixed-effects model or random-effects model to pool the estimates according to the heterogeneity between the included studies.

Results:

A total of 21 RCTs, which included 1679 patients, were included. Results revealed that telmisartan was superior in improving homeostasis model assessment of insulin resistance (mean difference = −0.23, 95% confidence interval [CI], −0.40 to −0.06), reducing fasting blood glucose level (mean difference = −0.32, 95% CI, −0.57 to −0.07), reducing fasting insulin level (mean difference = −1.01, 95% CI, −1.63 to −0.39), and decreasing diastolic blood pressure (mean difference = −1.46, 95% CI, −2.10 to −0.82) compared with other ARBs. However, for the decrease in systolic pressure, the difference was not statistically significant (mean difference = −0.73, 95% CI, −1.53 to 0.07).

Conclusion:

Telmisartan can better improve IR compared with other ARBs.
Lysosomal acid lipase and lipid metabolism: new mechanisms, new questions, and new therapies
Authors: Zhang Hanrui
Published: March 2018

Purpose of review

Lysosomal acid lipase (LAL), encoded by theLIPAgene, is an essential lysosomal enzyme that hydrolyzes cholesteryl ester and triglyceride delivered to the lysosome. This review highlights the novel pathophysiological role of LAL, the functional genomic discoveries ofLIPAas a risk locus for coronary heart diseases (CHD), and the clinical advance in therapies for LAL deficiency.

Recent findings

The essential role of LAL in lipid metabolism has been confirmed in human and mice with LAL deficiency. In humans, loss-of-function mutations ofLIPAcause rare lysosomal disorders, Wolman disease, and cholesteryl ester storage disease, in which LAL enzyme replacement therapy has shown significant benefits in a phase 3 clinical trial. Recent studies have revealed the role of LAL-mediated lysosomal lipolysis in regulating macrophage M2 polarization, lipid mediator production, VLDL secretion, lysosomal function and autophagy, extracellular degradation of aggregated-LDL, and adipose tissue lipolysis. Genome-wide association studies and functional genomic studies have identifiedLIPAas a risk locus for CHD, but the causal variants and mechanisms remain to be determined.

Despite years of research, our understanding of LAL is incomplete. Future studies will continue to focus on the key pathophysiological functions of LAL in health and diseases including CHD.
Overcoming developing-world challenges in cochlear implantation: a South American perspective
Authors: Bento Ricardo F. , Bahmad Fayez , Hippolyto Miguel A. , Da Costa Sady S.
Published: March 2018

Purpose of review

Effective hearing rehabilitation with cochlear implantation is challenging in developing countries, and this review focuses on strategies for childhood profound sensorineural hearing loss care in South America.

Recent findings

Most global hearing loss exists in developing countries; optimal cost-effective management strategies are essential in these environments. This review aims to assess and discuss the challenges of cochlear implantation effectiveness in South America. The authors searched electronic databases, bibliographies, and references for published and unpublished studies. Sensitivity analysis was performed to evaluate the effect of device cost, professional salaries, annual number of implants, and failure rate. Costs were obtained from experts in South America using known costs and estimations whenever necessary. Recent studies reported several challenges in unilateral or bilateral cochlear implants: cochlear implant costs, deaf education costs, increasing need for cochlear implant capacity, and training and increasing longevity.

Cochlear implantation was very cost-effective in all South American countries. Despite inconsistencies in the quality of available evidence, the robustness of systematic review methods substantiates the positive findings of the included studies, demonstrating that unilateral cochlear implantation is clinically effective and likely to be cost-effective in developing countries.
A comparison of neuromuscular electrical stimulation and traditional therapy, versus traditional therapy in patients with longstanding dysphagia
Authors: Frost Jo , Robinson H. Fiona , Hibberd Judi
Published: March 2018

Purpose of review

Dysphagia in adults arises from a range of causes including acquired neurological disorders and some cancers. Previous research has suggested that treatment using neuromuscular electrical stimulation (NMES) when used in conjunction with conventional therapy is effective. This review describes the recent literature and a small prospective case series carried out in the United Kingdom. This study contributed to support National Institute of Clinical Excellence (NICE) guidance for clinicians who wish to include NMES in a rehabilitation programme for dysphagic patients, specifically with reference to safety and the impact on swallowing function of this intervention.

Recent findings

In 2014, the UK NICE issued guidelines enabling UK therapists to trial the use of NMES, but the guidelines also sought additional evidence on the impact on swallowing function of NMES and the incidence of side effects. This small prospective case series investigated both of these aspects with a group of patients with dysphagia of neurological origin who had not achieved adequate swallowing function with traditional therapy alone. This study recruited 10 adult patients with dysphagia of neurological origin. All had previously received traditional swallowing therapy for at least 6 months but only achieved a Functional Oral Intake Scale of 4 or less (a scale for amounts and types of oral intake). The total study period was 10 weeks for each subject comprising 5 weeks of traditional therapy delivered three times a week followed by 5 weeks of NMES concurrent with traditional therapy (NMES + traditional therapy) delivered three times a week using the VitalStim stimulator (VitalStim Therapy, UK). In addition, the Quality of Life in Swallowing and Eating Assessment Tool 10 (quality of life scales) were determined to allow comparison between studies. Nine subjects achieved an improvement in swallowing function after NMES + traditional therapy was measured using the Functional Oral Intake Scale, giving a statistically significant improvement (P < 0.001) when NMES + traditional therapy was compared with traditional therapy. In addition, there was a low incidence of adverse effects with only minor adverse events occurring in 1.3% of electrode pair placements.

The current preliminary study suggests that NMES + traditional therapy has a good safety record and may improve oral intake and patient reported swallowing outcomes for subjects with long-standing dysphagia of neurological cause, which has not responded to traditional therapy. Provided care is taken with skin preparation and electrode placement the risk of adverse effects from the treatment was minimal. Significantly, in 30% of the subjects, an improvement in voice quality was found.
Sensory-Challenge Balance Exercises Improve Multisensory Reweighting in Fall-Prone Older Adults
Authors: Allison Leslie K. , Kiemel Tim , Jeka John J.
Published: March 2018

Background and Purpose:

Multisensory reweighting (MSR) deficits in older adults contribute to fall risk. Sensory-challenge balance exercises may have value for addressing the MSR deficits in fall-prone older adults. The purpose of this study was to examine the effect of sensory-challenge balance exercises on MSR and clinical balance measures in fall-prone older adults.

Methods:

We used a quasi-experimental, repeated-measures, within-subjects design. Older adults with a history of falls underwent an 8-week baseline (control) period. This was followed by an 8-week intervention period that included 16 sensory-challenge balance exercise sessions performed with computerized balance training equipment. Measurements, taken twice before and once after intervention, included laboratory measures of MSR (center of mass gain and phase, position, and velocity variability) and clinical tests (Activities-specific Balance Confidence Scale, Berg Balance Scale, Sensory Organization Test, Limits of Stability test, and lower extremity strength and range of motion).

Results:

Twenty adults 70 years of age and older with a history of falls completed all 16 sessions. Significant improvements were observed in laboratory-based MSR measures of touch gain (P = 0.006) and phase (P = 0.05), Berg Balance Scale (P = 0.002), Sensory Organization Test (P = 0.002), Limits of Stability Test (P = 0.001), and lower extremity strength scores (P = 0.005). Mean values of vision gain increased more than those for touch gain, but did not reach significance.

Discussion and Conclusions:

A balance exercise program specifically targeting multisensory integration mechanisms improved MSR, balance, and lower extremity strength in this mechanistic study. These valuable findings provide the scientific rationale for sensory-challenge balance exercise to improve perception of body position and motion in space and potential reduction in fall risk.
High-Intensity Variable Stepping Training in Patients With Motor Incomplete Spinal Cord Injury: A Case Series
Authors: Holleran Carey L. , Hennessey Patrick W. , Leddy Abigail L. , Mahtani Gordhan B. , Brazg Gabrielle , Schmit Brian D. , Hornby T. George
Published: March 2018

Background and Purpose:

Previous data suggest that large amounts of high-intensity stepping training in variable contexts (tasks and environments) may improve locomotor function, aerobic capacity, and treadmill gait kinematics in individuals poststroke. Whether similar training strategies are tolerated and efficacious for patients with other acute-onset neurological diagnoses, such as motor incomplete spinal cord injury (iSCI), is unknown. Individuals with iSCI potentially have greater bilateral impairments. This case series evaluated the feasibility and preliminary short- and long-term efficacy of high-intensity variable stepping practice in ambulatory participants for more than 1 year post-iSCI.

Case Series Description:

Four participants with iSCI (neurological levels C5-T3) completed up to 40 one-hour sessions over 3 to 4 months. Stepping training in variable contexts was performed at up to 85% maximum predicted heart rate, with feasibility measures of patient tolerance, total steps/session, and intensity of training. Clinical measures of locomotor function, balance, peak metabolic capacity, and gait kinematics during graded treadmill assessments were performed at baseline and posttraining, with more than 1-year follow-up.

Outcomes:

Participants completed 24 to 40 sessions over 8 to 15 weeks, averaging 2222 ± 653 steps per session, with primary adverse events of fatigue and muscle soreness. Modest improvements in locomotor capacity where observed at posttraining, with variable changes in lower extremity kinematics during treadmill walking.

Discussion:

High-intensity, variable stepping training was feasible and tolerated by participants with iSCI although only modest gains in gait function or quality were observed. The utility of this intervention in patients with more profound impairments may be limited.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A200)
Retrospective Application of New Pediatric Ventilator-Associated Pneumonia Criteria Identifies a High-Risk Population*
Authors: Gionfriddo Ashley , Nonoyama Mika L. , Laussen Peter C. , Cox Peter N. , Clarke Megan , Floh Alejandro A.
Published: March 2018

Objectives:

To promote standardization, the Centers for Disease Control and Prevention introduced a new ventilator-associated pneumonia classification, which was modified for pediatrics (pediatric ventilator-associated pneumonia according to proposed criteria [PVAP]). We evaluated the frequency of PVAP in a cohort of children diagnosed with ventilator-associated pneumonia according to traditional criteria and compared their strength of association with clinically relevant outcomes.

Design:

Retrospective cohort study.

Setting:

Tertiary care pediatric hospital.

Patients:

Critically ill children (0–18 yr) diagnosed with ventilator-associated pneumonia between January 2006 and December 2015 were identified from an infection control database. Patients were excluded if on high frequency ventilation, extracorporeal membrane oxygenation, or reintubated 24 hours following extubation.

Interventions:

None.

Measurements and Main Results:

Patients were assessed for PVAP diagnosis. Primary outcome was the proportion of subjects diagnosed with PVAP. Secondary outcomes included association with intervals of care. Two hundred seventy-seven children who had been diagnosed with ventilator-associated pneumonia were eligible for review; 46 were excluded for being ventilated under 48 hours (n = 16), on high frequency ventilation (n = 12), on extracorporeal membrane oxygenation (n = 8), ineligible bacteria isolated from culture (n = 8), and other causes (n = 4). ICU admission diagnoses included congenital heart disease (47%), neurological (16%), trauma (7%), respiratory (7%), posttransplant (4%), neuromuscular (3%), and cardiomyopathy (3%). Only 16% of subjects (n = 45) met the new PVAP definition, with 18% (n = 49) having any ventilator-associated condition. Failure to fulfill new definitions was based on inadequate increase in mean airway pressure in 90% or Fio
2 in 92%. PVAP was associated with prolonged ventilation (median [interquartile range], 29 d [13–51 d] vs 16 d [8–34.5 d]; p = 0.002), ICU (median [interquartile range], 40 d [20–100 d] vs 25 d [14–61 d]; p = 0.004) and hospital length of stay (median [interquartile range], 81 d [40–182 d] vs 54 d [31–108 d]; p = 0.04), and death (33% vs 16%; p = 0.008).

Conclusions:

Few children with ventilator-associated pneumonia diagnosis met the proposed PVAP criteria. PVAP was associated with increased morbidity and mortality. This work suggests that additional study is required before new definitions for ventilator-associated pneumonia are introduced for children.
Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery
Authors: Goot Benjamin H. , Kaufman Jon , Pan Zhaoxing , Bourne David W. A. , Hickey Francis , Twite Mark , Galinkin Jeffrey , Christians Uwe , Zuk Jeannie , da Cruz Eduardo M.
Published: March 2018

Objectives:

To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome.

Design:

Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics.

Setting:

A 16-bed cardiac ICU at an university-affiliated hospital.

Patients:

Forty-two patients (20 Down syndrome, 22 controls) were enrolled.

Interventions:

None.

Measurements and Main Results:

The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant.

Conclusions:

This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.
Facilitating Weight Shifting During Treadmill Training Improves Walking Function in Humans With Spinal Cord Injury
Authors: Wu Ming , Kim Janis , Wei Feng
Published: March 2018

Objective

The aim of the study was to determine whether the integration of dynamic weight shifting into treadmill training would improve the efficacy of treadmill training in humans with spinal cord injury.

Design

Sixteen humans with spinal cord injury were randomly assigned to receive robotic or treadmill-only training and underwent 6 wks of training. A force was applied to the pelvis for facilitating weight shifting and to the legs for assisting with leg swing for participants in the robotic group. No assistance force was applied for participants in the treadmill-only group. Outcome measures consisted of overground walking speed, 6-min walking distance, and other clinical measures and were assessed before, after 6 wks of training, and 8 wks after the end of training.

Results

A greater improvement in 6-min walking distance was observed after robotic training than that after treadmill-only training (P = 0.03), but there was not a significant difference between the two groups in improvements in walking speed. However, a greater improvement was observed for the participants who underwent robotic training than those who underwent treadmill-only training (i.e., 15% vs. 2%).

Conclusions

Applying a pelvis assistance force for facilitating weight shifting during treadmill training may improve locomotor function in humans with spinal cord injury.
Chronic postsurgical pain and cancer: the catch of surviving the unsurvivable
Authors: Humble Stephen R. , Varela Nicolas , Jayaweera Asantha , Bhaskar Arun
Published: March 2018

Purpose of review

Chronic postsurgical pain (CPSP) is an important and well recognized cause of much long-term suffering, which in some cases may be preventable and affects many people living with cancer. Unfortunately, general consensus is lacking as to how best reduce the risk of developing CPSP.

Recent findings

Cancer is now not always a short-lived, fatal disease and is now moving towards a chronic illness. Poorly managed perioperative pain is the greatest risk factor for CPSP. Recent trials have examined preventive strategies for CPSP associated with breast surgery and thoracotomy, two operations used in cancer treatment. Standard antinociceptive drugs, 5% lidocaine patches and ketamine do not prevent CPSP. The evidence for gabapentinoids is conflicting. Intravenous lidocaine and, separately, regional anaesthesia appear beneficial.

Well-managed pain, irrespective of technique, reduces the risk of CPSP. The literature is inconclusive regarding an ‘optimal approach.’ Regional anaesthesia, intravenous lidocaine and the aggressive management of perioperative pain using multimodal analgesia including antineuropathic pain agents such as gabapentinoids and certain antidepressants are recommended. Clinicians should not rely on general anaesthesia, opioids, NSAIDs and ketamine to prevent CPSP. A blanket approach using gabapentinoids for all patients undergoing major surgery is not indicated. Instead, the presence of perioperative neuropathic pain should be checked for regularly.
Clinical and Electrographic Correlates of Bilateral Independent Periodic Discharges
Authors: Freund Brin , Gugger James J. , Reynolds Alexandra , Tatum William O. , Claassen Jan , Kaplan Peter W.
Published: March 2018

Purpose:

Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described.

Methods:

We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs.

Results:

Twenty-five patients studied with a mean Glasgow Coma Scale 6.5 and modified Rankin scale 3.9 who underwent EEG monitoring, mean duration 287 hours (range 0.75–3,216). Most common causes of BIPDs were cardiac arrest, Central Nervous System infections, and acute/chronic ischemic/hemorrhagic stroke. Most had subcortical and cortical injuries on neuroimaging. Most of the PDs ranged from 0.5 to 2 Hz in frequency, were of multiple phase types, and localized to the frontal head regions. Eighteen of 25 patients had clinical or electrographic seizures. There was a trend toward seizures in those with BIPDs with a history of epilepsy (P = 0.08) and acute metabolic dysfunction (P = 0.08), particularly with coincident acute structural lesions (P = 0.05). Seizures were predicted by bilaterally symmetric frequencies (P = 0.02) and trended toward higher likelihood with PD frequency <2 Hz (P = 0.08). Two of 25 patients survived past discharge with modified Rankin scale <3. Cardiac arrest was associated with withdrawal of life-sustaining therapy (P < 0.001).

Conclusions:

BIPDs arise from acute and chronic neurologic injuries, often associated with metabolic dysfunction. Outcomes are poor in this population. Seizures are common, particularly in patients with PDs that are of a lower frequency or are symmetric in frequency. Further study is warranted to evaluate the association between BIPDs and seizures, as well as functional and longer term outcomes.
Uncovering novel pathways for enhancing hyaluronan synthesis in recombinantLactococcus lactis: Genome-scale metabolic modelling and experimental validation
Authors: Badri Abinaya , Raman Karthik , Jayaraman Guhan
Published: March 2018

Hyaluronan (HA) is a naturally occurring high-value polysaccharide with important medical applications. HA is commercially produced from pathogenic microbial sources. HA-producing recombinant cell factories that are being developed with GRAS organisms are comparatively less productive than the best natural producers. The metabolism of these recombinant systems needs to be more strategically engineered to achieve significant improvement. Here, we use a genome-scale metabolic network model to account for the entire metabolic network of the cell to predict strategies for improving HA production. We here analyze the metabolic network ofLactococcus lactisadapted to produce HA, and identify non-conventional overexpression and knock-out strategies to enhance HA flux.

To experimentally validate our predictions, we identify an alternate route for enhancement of HA synthesis, originating from the nucleoside inosine, which has the capacity to function in parallel with the traditionally known route from glucose. Adopting this strategy resulted in a 2.8-fold increase in HA yield. The strategies identified and the experimental results show that the cell is capable of involving a larger subset of metabolic pathways in HA production. Apart from being the first report of the use of a nucleoside to improve HA production, our study shows how experimental results enable model refinement. Overall, we point out that well-constructed genome-scale metabolic models could be very potent tools to derive efficient strategies to improve biosynthesis of important high-value products.
Pollen Patterns Form from Modulated Phases
Authors: Radja Asja , Horsley Eric M. , Lavrentovich Maxim O. , Sweeney Alison M.
Published: March 2018

Pollen grains are known for their impressive variety of species-specific, microscale surface patterning. Despite having similar biological developmental steps, pollen grain surface features are remarkably geometrically varied. Previous work suggests that a physical process may drive this pattern formation and that the observed diversity of patterns can be explained by viewing pollen pattern development as a phase transition to a spatially modulated phase. Several studies have shown that the polysaccharide material of plant cell walls undergoes phase separation in the absence of cross-linking stabilizers of the mixed phase. Here we show experimental evidence that phase separation of the extracellular polysaccharide material (primexine) during pollen cell development leads to a spatially modulated phase. The spatial pattern of this phase-separated primexine is also mechanically coupled to the undulation of the pollen cell membrane. The resulting patterned pools of denser primexine form the negative template of the ultimate sites of sporopollenin deposition, leading to the final micropattern observed in the mature pollen. We then present a general physical model of pattern formation via modulated phases. Using analytical and numerical techniques, we find that most of the pollen micropatterns observed in biological evolution could result from a physical process of modulated phases. However, an analysis of the relative rates of transitions from states that are equilibrated to or from states that are not equilibrated suggests that while equilibrium states of this process have occurred throughout evolutionary history, there has been no particular evolutionary selection for symmetric, equilibrated states.