bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the CMS No-Pay Policy on Hospital-Acquired Fall Prevention Related Practice Patterns
Authors: Fehlberg Elizabeth A , Lucero Robert J , Weaver Michael T , McDaniel Anna M , Chandler Michelle , Richey Phyllis A , Mion Lorraine C , Shorr Ronald I
Published: February 2018

Background and Objectives

In October 2008, the Centers for Medicare & Medicaid Services (CMS) stopped reimbursing hospitals for costs related to patient falls. This study aimed to examine whether the CMS no-pay policy influenced four fall prevention practices: bed alarms, sitters, room changes, and physical restraints.

Research Design and Methods

Using electronic medical record data collected from four hospitals between 2005 and 2010, this secondary observational analysis examined the associations between the CMS no-pay policy and nursing interventions and medical orders related to fall prevention. Multivariable generalized linear mixed models with logit link function and accommodation for matching was used to assess the associations between the CMS no-pay policy and nursing interventions and medical orders.

Results

After the CMS policy change, nurses were more likely to perform one or more fall-related interventions (adjusted odds ratio (aOR): 1.667; 95% confidence interval (CI): 1.097–2.534). Of the four prevention practices, the use of bed alarms (aOR: 2.343; 95% CI: 1.409–3.897) increased significantly after the CMS policy change.

Discussion and Implications

The CMS no-pay policy increased utilization of fall prevention strategies despite little evidence that these measures prevent falls.
Common octopus settled in human-altered Mediterranean coastal waters: from individual home range to population dynamics
Authors: Arechavala-Lopez P , Minguito-Frutos M , Follana-Berná G , Palmer M
Published: February 2018

A spatially explicit capture-recapture (SCR) model was applied to estimate simultaneously population parameters and individual activity (i.e. home range size) of O. vulgaris, based on experimental mark-recapture data in a human-altered Mediterranean coastal area. Seventy-two octopuses were captured, tagged with subcutaneous PIT-tags and released. Nineteen tagged individuals were recaptured (recapture rate: 26.4%) in the same area over the study period, which spanned over 6 months. Population sizes and densities decreased over the study period, from 337 octopuses (8 ind. ha−1) in September-October to 105 octopuses (2.5 ind. ha−1) in February-March. The highest recruitment probability was estimated to occur at the beginning of the study but it clearly decreased over time, while mortality probability during a fishing period slightly increased. Mean specific growth rate was 0.82 ± 0.11 day−1. Individual home range or activity area ranged from 2.8 ha to 7.3 ha (median home range radius: 121.8 m). Overall, these results suggest that human-altered coastal habitats, which are characterized by abundant shelters, abundant food and absence of predators, can act as settlement and growth areas for juveniles and adults of O. vulgaris. Furthermore, the methodologies applied in this study are recommended as innovative tools to improve management actions of coastal resources.
Can online social support be detrimental in stigmatized chronic diseases? A quadratic model of the effects of informational and emotional support on self-care behavior of HIV patients
Authors: Wang Xunyi , Parameswaran Srikanth , Bagul Darshan Mahendra , Kishore Rajiv
Published: February 2018

Objective

We studied the impact of online social support on patient self-care behavior in an online health community for human immunodeficiency virus (HIV) patients. We conceptualized emotional and informational support provided by community members into nuanced sub-dimensions. We explored how the direct and interaction effects of these sub-dimensions impact the self-care behavior of a support seeker.

Methods

We used data from 330 255 posts in 30 050 threads from POZ, an online health community for HIV patients. Our key variables—self-care behaviori, objective informationj, experiential supportj, and emotional tonej—were operationalized using linguistic analysis with self-generated dictionaries and Python libraries. We tested our hypotheses using Tobit regression.

Results

Out of 6 null hypotheses, 5 were rejected. Objective information and emotional tone had an inverted-U relationship with self-care behavior. Experiential information and community involvement were positively related to self-care behavior. Community involvement amplified the inverted-U relationship between emotional tone and self-care behavior. No significant interaction effect was found between experiential support and objective information.

Conclusions

Beyond a threshold, both informational and emotional online social support had a deleterious impact on self-care behavior of HIV patients. Our results suggested that caution should be exercised in the use of online health community interventions for HIV patients, and perhaps patients with other stigmatized chronic diseases.
Identification of Global and Local Shocks in International Financial Markets via General Dynamic Factor Models*
Authors: Barigozzi Matteo , Hallin Marc , Soccorsi Stefano
Published: February 2018

We employ a two-stage general dynamic factor model to analyze co-movements between returns and between volatilities of stocks from the U.S., European, and Japanese financial markets. We find two common shocks driving the dynamics of volatilities—one global shock and one United States–European shock—and four local shocks driving returns, but no global one. Co-movements in returns and volatilities increased considerably in the period 2007–2012 associated with the Great Financial Crisis and the European Sovereign Debt Crisis. We interpret this finding as the sign of a surge, during crises, of interdependencies across markets, as opposed to contagion. Finally, we introduce a new method for structural analysis in general dynamic factor models which is applied to the identification of volatility shocks via natural timing assumptions. The global shock has homogeneous dynamic effects within each individual market but more heterogeneous effects across them, and is useful for predicting aggregate realized volatilities.
Cleaved β-Actin May Contribute to DNA Fragmentation Following Very Brief Focal Cerebral Ischemia
Authors: Ye Zhouheng , Ander Bradley P , Sharp Frank R , Zhan Xinhua
Published: February 2018

Our previous study demonstrated caspase independent DNA fragmentation after very brief cerebral ischemia, the mechanism of which was unclear. In this study, we explore whether actin is cleaved following focal cerebral ischemia, and whether these structural changes of actin might modulate DNA fragmentation observed following focal ischemia. Results showed that a cleaved β-actin fragment was identified in brains of rats 24 hours following 10-minute and 2-hour focal ischemia. Though granzyme B and caspase-3 cleaved β-actin in vitro, the fragment size of β-actin cleaved by granzyme B was the same as those found after 10-minute and 2-hour focal ischemia. This was consistent with increases of granzyme B activity after 10-minute and 2-hour ischemia compared with controls. Cerebral extracts from 10-minute and 2-hour ischemic brains degraded DNA in vitro. Adding intact β-actin to these samples completely abolished DNA degradation from the 10-minute ischemia group but not from the 2-hour ischemia group. We concluded that β-actin is likely cleaved by granzyme B by 24 hours following 10-minute and 2-hour focal cerebral ischemia. Intact β-actin inhibits DNase, and cleavage of β-actin activates DNase, which leads to DNA fragmentation observed in the brain following very brief focal ischemia.
Vision loss in glioblastoma: Disease mimicking presumed therapeutic toxicity
Authors: Nguyen HuyTram N , Vo Kevin B H , Howard Steven , Salamat M Shahriar , Rowely Howard , Robins H Ian
Published: February 2018

Glioblastoma is the most common and lethal form of primary brain cancer. In the recurrent setting, bevacizumab is a common choice for salvage therapy. Loss of vision in patients initially treated with radiation at the time of diagnosis and later treated with bevacizumab at time of recurrence has been reported, and presumed to be a treatment-related optic neuropathy. Strikingly, only 1 case report described a postmortem biopsy to rule out tumor involvement of the optic tracts. We report the first case of recurrent glioblastoma infiltrating the prechiasmatic and chiasmatic optic nerve, which at the time of vision loss was presumed to be secondary to bevacizumab. It is noteworthy that the MRI findings in the previously reported bevacizumab/radiation-induced optic neuropathy cases (without pathology follow-up) are comparable to our patient.
HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe
Authors: Chimbetete Cleophas , Katzenstein David , Shamu Tinei , Spoerri Adrian , Estill Janne , Egger Matthias , Keiser Olivia
Published: February 2018

Objectives

To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe.

Methods

Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir.

Results

Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3–5.1) and 2.6 years (IQR, 1.6–4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728–208 920 copies/mL) and 201 cells/mm3 (IQR, 49–333 cells/mm3). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years (P = .003) and CD4 cell count <200 cells/mm3 (P = .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69–13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months.

Conclusions

The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.
Detailed CO(J = 1–0, 2–1, and 3–2) observations toward an H ii region RCW 32 in the Vela Molecular Ridge
Authors: Enokiya Rei , Sano Hidetoshi , Hayashi Katsuhiro , Tachihara Kengo , Torii Kazufumi , Yamamoto Hiroaki , Hattori Yusuke , Hasegawa Yutaka , Ohama Akio , Kimura Kimihiro , Ogawa Hideo , Fukui Yasuo
Published: February 2018

We performed CO(J = 1–0, 2–1, and 3–2) observations toward an H ii region RCW 32 in the Vela Molecular Ridge. The CO gas distribution associated with the H ii region was revealed for the first time at a high resolution of 22″. The results revealed three distinct velocity components which show correspondence with the optical dark lanes and/or Hα distribution. Two of the components show complementary spatial distribution which suggests collisional interaction between them at a relative velocity of ∼ 4 km s−1. Based on these results, we present a hypothesis that a cloud–cloud collision determined the cloud distribution and triggered formation of the exciting star ionizing RCW 32. The collision time scale is estimated from the cloud size and the velocity separation to be ∼2 Myr and the collision terminated ∼1 Myr ago, which is consistent with the age of the exciting star and the associated cluster. By combing the previous works on the H ii regions in the Vela Molecular Ridge, we argue that the majority (at least four) of the H ii regions in the Ridge were formed by triggering of cloud–cloud collision.
The Geography of NGO Activism against Multinational Corporations
Authors: Hatte Sophie , Koenig Pamina
Published: February 2018

To what extent do Non-Governmental Organizations (NGOs) monitor global value chains? While NGOs regularly denounce the behavior of multinational corporations throughout the world, their motivations for choosing campaign targets remain largely unknown. Using a new dataset on activists’ campaigns toward multinational firms, we estimate a triadic gravity equation for campaigns, involving the NGO, firm, and action countries. Our results point to a strong proximity bias in NGO activity: Distance, national borders, and lack of a common language all contribute to impede the intensity of campaigns. We estimate the distance elasticity of campaigns to be −0.2 and further document that NGOs strongly bias their actions toward home firms or foreign firms with home actions. A domestic firm is 3.45 times more likely to be attacked than a foreign one. Foreign firms headquartered in common language countries draw 1.63 times more campaigns. Overall, campaigns seem to be designed so as to include at least one element of proximity drawing the attention of consumers. This pattern questions the role of NGOs in the monitoring of multinational production operated in remote, unfamiliar locations.
Bacterial Gall of Loropetalum chinense caused by Pseudomonas amygdali pv. loropetali pv. nov.
Authors: Harmon Carrie Lapaire , Timilsina Sujan , Bonkowski John , Jones Debra D. , Sun Xiaoan , Vallad Gary E. , Sepulveda Laura Ramos , Bull Carolee , Jones Jeffrey B.
Published: February 2018

In 2012, stem gall samples on Loropetalum chinense were sent to Florida diagnostic labs from Alabama and Florida nurseries. A fluorescent pseudomonad was consistently isolated from the galls. The organism was originally identified in Alabama based on 16S rRNA sequencing as Pseudomonas savastanoi, which causes a production-limiting disease of olive. The loropetalum strains and reference strains were compared using LOPAT, Biolog, fatty acid analysis, multilocus sequence analysis (MLSA), and pathogenicity tests. The LOPAT tests placed the loropetalum strains within Pseudomonas syringae. Biolog and fatty acid analysis placed the strains in various pathovars of P. syringae and P. savastanoi, respectively. MLSA of a set of housekeeping genes separated the loropetalum strains from the olive knot-inducing strains. Our work indicates there is a need to use more tests than 16S rRNA to accurately diagnose new bacterial diseases. In pathogenicity tests, the loropetalum strains produced galls only on loropetalum, but not on olive, mandevilla, or almond, indicating this strain is not a threat to the olive industry. Based on the pathogenicity assays and molecular tests, loropetalum strains represent a distinct and new pathovar, P. amygdali pv. loropetali pv. nov., for which the strain PDC13-208 (= DSMZ 105780PT) has been designated as the pathotype strain.
Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling
Authors: Angel Chelsea , Glovak Zachary T. , Alami Wateen , Mihalko Sara , Price Josh , Jiang Yandong , Baghdoyan Helen A. , Lydic Ralph
Published: February 2018

Background

Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing.

Methods

Mice (n = 40 male and 40 female) comprising four congenic lines that differ in leptin signaling and body weight were injected with saline and buprenorphine (0.3 mg/kg). Whole-body plethysmography was used to quantify the effects on minute ventilation. The data were evaluated using three-way analysis of variance, regression, and Poincaré analyses.

Results

Relative to B6 mice with normal leptin, buprenorphine decreased minute ventilation in mice with diet-induced obesity (37.2%; P < 0.0001), ob/ob mice that lack leptin (62.6%; P < 0.0001), and db/db mice with dysfunctional leptin receptors (65.9%; P < 0.0001). Poincaré analyses showed that buprenorphine caused a significant (P < 0.0001) collapse in minute ventilation variability that was greatest in mice with leptin dysfunction. There was no significant effect of sex or body weight on minute ventilation.

Conclusions

The results support the interpretation that leptin status but not body weight or sex contributed to the buprenorphine-induced decrease in minute ventilation. Poincaré plots illustrate that the buprenorphine-induced decrease in minute ventilation variability was greatest in mice with impaired leptin signaling. This is relevant because normal respiratory variability is essential for martialing a compensatory response to ventilatory challenges imposed by disease, obesity, and surgical stress.
Nail Fit: Does Nail Diameter to Canal Ratio Predict the Need for Exchange Nailing in the Setting of Aseptic, Hypertrophic Femoral Nonunions?
Authors: Millar Michael J. , Wilkinson Andrew , Navarre Pierre , Steiner Joel , Vohora Ashray , Hardidge Andrew , Edwards Elton
Published: February 2018

Objectives:

To evaluate patient-independent risk factors for aseptic femoral hypertrophic nonunion requiring exchange nailing, with particular reference to the fit of the nail at the isthmus within the canal.

Design:

Retrospective case control study.

Setting:

Level 1 trauma center.

Main Outcome Measurements:

Between 2008 and 2012, 211 patients without any patient-dependent risk factors for nonunion were treated with a locked reamed intramedullary nail for a femoral shaft fracture. Twenty-three cases went on to hypertrophic nonunion requiring exchange nailing (treatment group) and 188 cases went on to union (control group). Patient-independent risk factors for exchange nailing were documented.

Results:

Patient-independent risk factors for exchange nailing were poor fracture reduction [Odds ratio (OR): 11.5, 95% confidence interval (CI), 4.0–33.4, P < 0.001], open fracture (OR: 7.6, 95% CI, 3.0–19.6, P = 0.004), Winquist classification of 4 (OR: 4.4, 95% CI, 1.9–6.7, P = 0.016), and poor nail fit (OR: 10.3, 95% CI, 5.1–28.4, P < 0.001). Multivariate analysis revealed nail fit as an independent predictor of femoral nonunion requiring exchange nailing (OR: 11.4, 95% CI, 6.9–15.2, P < 0.001). Moreover, we found a direct relationship between increasingly poor nail fit and increased risk of exchange nailing, with the criterion occurring at a nail fit ratio <70%.

Conclusion:

When proceeding to femoral fracture reamed intramedullary nailing, we recommend a minimum nail fit of 70% at the isthmus and ideally 90% or more, to avoid surgical reintervention.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Intraoperative Vancomycin Powder Reduces Staphylococcus aureus Surgical Site Infections and Biofilm Formation on Fixation Implants in a Rabbit Model
Authors: Hovis James Paul , Montalvo Ryan , Marinos Dimitrius , Joshi Manjari , Shirtliff Mark E. , O'Toole Robert V. , Manson Theodore T.
Published: February 2018

Objectives:

To evaluate the effectiveness of intraoperative vancomycin powder in prevention of surgical site infection and biofilm formation on implants in a contaminated animal fixation model.

Methods:

We created a rabbit surgical model including fixation implants at a tibial surgical site seeded with methicillin-resistant Staphylococcus aureus. Our study cohort included 18 rabbits. Nine received vancomycin powder at the surgical site, and the other 9 did not. Serum vancomycin levels were measured at scheduled time points over 24 hours. Bone infection and implant biofilm formation were determined based on the number of colony-forming units present 2 weeks after surgery. Radiography, histology, and electron microscopy aided in evaluation.

Results:

No bone infection or implant colonization occurred in the vancomycin powder group. Six bone infections and 6 implant biofilm formations (67%; 95% confidence interval, 45%–88%) occurred in the group that did not receive vancomycin powder (P = 0.009). Serum vancomycin levels were detectable at minimal levels at 1 and 6 hours only. Pathological changes occurred in the specimens that were positive for infection.

Conclusions:

Intraoperative vancomycin powder application at the time of fixation decreases risk for bone infection and biofilm formation on implants in a rabbit model, with minimal increase in serum vancomycin levels. The results are encouraging and support the rationale for a clinical trial investigating the use of local vancomycin powder to reduce the rate of surgical site infections.

Clinical Relevance:

Infection is a common complication of surgery, especially with implants. Simple methods to prevent or decrease the occurrence of infection would benefit the patient and the health care system.
What Is the Ideal Starting Point for an Olecranon Screw? An Anatomic Cadaveric Study
Authors: Potter G. David , Mascarenhas Daniel , Sciadini Marcus F. , Carlini Anthony R. , O'Toole Robert V. , Pensy Raymond A.
Published: February 2018

Objective:

To assess whether “center-center” position is ideal starting point for minimum fracture displacement when placing an intramedullary (IM) screw in the ulna.

Methods:

Thirty-six arms (average age, 82 years) underwent a posterior approach to the olecranon and were randomized into 3 groups: center-center (center in sagittal plane, center in coronal plane), posterior-lateral (posterior in sagittal plane, lateral in coronal plane), and posterior-medial (posterior in sagittal plane, medial in coronal plane). Groups were matched into 18 pairs, and fixation was performed with an IM screw. Primary outcome measure was articular surface displacement on the olecranon. Measurements were compared across each combination of locations using the Kruskal-Wallis rank sums test, and a sign test determined whether each location differed from anatomic reduction.

Results:

Articular step-off measurements were significantly different between center-center (0.6 mm) and posterior-medial (2.1 mm) groups (P = 0.01) and approached significance with posterior-lateral versus posterior-medial (0.9 mm) locations (P = 0.07). No significant difference was found comparing center-center with posterior-lateral locations (P = 0.7). The articular surface (P = 0.04), posterior cortex (P = 0.02), and medial cortex (P = 0.001) measurements for the posterior-medial starting point were all worse compared with anatomic reduction.

Conclusions:

Malreduction of a simulated olecranon fracture was most significant when the starting point for the IM screw was malpositioned medially. A central or laterally based starting point was more forgiving. Avoiding a medially based starting point is crucial for achieving benefits of fixation with an IM screw and reduces the chance of malreduction after fixation.
The Economic Burden of Musculoskeletal Disease in Children and Adolescents in the United States
Authors: Rosenfeld Scott B. , Schroeder Katherine , Watkins-Castillo Sylvia I.
Published: February 2018

Background:

Musculoskeletal conditions are among the most common and costly conditions suffered by Americans. In 2011, there was an estimated $213 billion in annual cost of direct treatment for and lost wages due to musculoskeletal disease in the United States. Data on economic burden, however, comes mostly from the adult population, with significantly less information regarding the burden of these conditions in young patients available. The purpose of this report is to provide data on the economic burden of musculoskeletal diseases in children and adolescents in the United States.

Methods:

Eleven diagnosis categories were identified, with health care visits and hospitalization data derived from ICD-9-CM codes for each of the conditions searched. The largest database utilized was the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Database (KID). Total visits came from the KID, HCUP NEDS (emergency department), NCHS NHAMCS OP (outpatient), and NCHS NAMCS (physician office) databases. The National Health Interview Survey (NHIS) child sample was additionally searched to obtain patient/parent-reported data.

Results:

In 2012, more than 19 million children and adolescents received treatment in medical centers, physicians’ offices, and hospitals for a musculoskeletal-related condition. The most common reason for treatment (68%) was traumatic injury, followed by a pain syndrome (13%) and deformity (9%). Total hospital charges in 2012 for children and adolescents with a primary musculoskeletal-related diagnosis totaled $7.6 billion. Trauma (43%) and deformity (38%) were the major contributors to total hospital charges.

Conclusions:

Although we found that hospital-related charges for musculoskeletal diseases for children and adolescents in 2012 totaled $7.6 billion, this number underestimates the total cost for all pediatric musculoskeletal conditions. Musculoskeletal conditions accounted for 5.4% of hospital charges in the pediatric population. However, only 1.4% of pediatric research funding is designated to musculoskeletal research. Going forward, the data in this report may be used to further research and to stimulate development of better methods with which to measure the direct and indirect costs of musculoskeletal conditions in children.

Level of Evidence:

Level IV—economic and decision analysis.
Neurovascular Changes Associated With the Water Drinking Test
Authors: Gameiro Gustavo , Monsalve Pedro , Golubev Iuri , Ventura Lori , Porciatti Vittorio
Published: February 2018

Purpose:

The water drinking test (WDT) is currently used to temporarily elevate intraocular pressure (IOP) and predict peak IOP in glaucoma. This study investigates neurovascular changes associated with WDT in normal subjects.

Methods:

The effect of WDT (1 L in 5 min) on IOP, mean brachial blood pressure, heart rate, and pattern electroretinogram was assessed within the next hour in 16 healthy subjects (mean age: 33.5±7.9 y). As a control, testing was repeated in the same subjects without WDT 1 week later.

Results:

Compared with control, WDT resulted in significant peak changes of the following parameters compared with baseline: IOP: +1.7±1.8 mm Hg after 30′, mean brachial blood pressure: +3.9±6.3 mm Hg after 15′; heart rate: −9.2±9.8 bpm after 15′, pattern electroretinogram latency: +2.1±0.9 ms after 15′.

Conclusions:

In addition to IOP elevation, WDT was associated with significant changes of hemodynamic parameters and retinal ganglion cell function in young healthy subjects. As these represent risk factors for glaucoma, their assessment upon WDT might increase its predictive power for glaucoma development.
Meibomian Gland Features and Conjunctival Goblet Cell Density in Glaucomatous Patients Controlled With Prostaglandin/Timolol Fixed Combinations: A Case Control, Cross-sectional Study
Authors: Agnifili Luca , Mastropasqua Rodolfo , Fasanella Vincenzo , Brescia Lorenza , Scatena Barbara , Oddone Francesco , Mastropasqua Leonardo
Published: February 2018

Purpose:

To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs).

Materials and Methods:

In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD.

Results:

PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05).

Conclusions:

PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.
The Longitudinal Effect of Vertigo and Dizziness Symptoms on Psychological Distress
Authors: Radziej Katharina , Probst Thomas , Limburg Karina , Dinkel Andreas , Dieterich Marianne , Lahmann Claas
Published: February 2018

Despite the frequent observation that vertigo and dizziness (VD) disorders may trigger or exacerbate secondary psychiatric comorbidities, there is limited understanding of the mechanisms underlying this development. To address this gap, we investigated whether symptom-related fears and cognitions as indicated by questionnaire-based measures are mediators of the longitudinal effect of VD symptoms on anxiety and depression after 1 year. We analyzed data from a large study with patients of a treatment center specialized in vertigo (N= 210). Simple and multiple parallel mediation models strengthened our hypothesis that fear of bodily sensations and cognitions about these symptoms play a mediating role in the relationship between VD symptoms and psychopathology at follow-up after baseline scores of the outcome were controlled for. Results are discussed within a cognitive theory framework and point to the potential benefits of interventions that modify symptom-related beliefs and fears via cognitive psychotherapy in this therapeutically underserved population.
Pure Intralymphatic Invasion in the Absence of Stromal Invasion After Neoadjuvant Therapy
Authors: Guilbert Marie-Christine , Overmoyer Beth , Lester Susan C.
Published: February 2018

Rarely is intralymphatic/lymph-vascular invasion (LVI) the only residual disease in the breast after neoadjuvant chemotherapy. Only 12 patients have been reported in 2 prior studies. Prognosis was poor, with only 2 patients remaining alive and disease-free. The purpose of this study was to gather more data on this pattern of residual disease. Cases in which LVI was the only residual disease in the breast were retrospectively identified. Eighteen cases were identified including 10 of 669 (1.5%) consecutive surgical cases between 2003 and 2015. The mean tumor size was 3.4 cm. Seven cancers were negative for estrogen receptor and HER2, 8 were HER2 positive, and 3 were estrogen receptor positive and HER2 negative. In 15 cases, lymph nodes were either suspicious by imaging or proven positive by biopsy. After neoadjuvant chemotherapy, 9 patients were node negative, 7 were node positive, and 2 had isolated tumor cells. Mean follow-up was 63.8 months (7 to 138 mo). Two deaths occurred in patients with positive nodes. One death occurred and 2 patients are alive with metastatic disease in the node-negative group. The remaining 13 patients are alive without disease. The outcome associated with residual LVI might not be as dismal as previously reported. Although the better outcome may be due to stage at presentation or the type of chemotherapy, it is difficult to compare the cohorts of the 3 studies. However, the death of 3 of 13 node-negative patients over the 3 studies supports not classifying residual LVI as a pathologic complete response.
Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children*
Authors: Genuini Mathieu , Oualha Mehdi , Bouazza Naïm , Moulin Florence , Treluyer Jean-Marc , Lesage Fabrice , Renolleau Sylvain , Benaboud Sihem
Published: February 2018

Objective:

Describe and assess a continuous infusion dosing scheme of vancomycin therapy in critically ill children.

Design:

Retrospective single-center study, January to June 2015.

Setting:

PICU located within a French tertiary academic pediatric hospital.

Patients:

All children admitted in the PICU from January 2015 to June 2015, receiving continuous infusion of vancomycin therapy.

Interventions:

None.

Measurements and Main Results:

Clinical and biological data, vancomycin dosing information, and plasma concentrations were recorded. Using a previously published population pharmacokinetics model, pharmacokinetic parameters were derived for each patient and vancomycin concentrations described after the loading dose. Areas under the curve were estimated for each patient, and an initial covariate-adjusted dose was calculated for every patient. A total of 87 vancomycin concentrations were analyzed from 28 patients between 1 month and 17 years old. The median (range) loading dose was 14.8 (12–16) mg/kg followed by a continuous infusion of vancomycin of 44 (35–61) mg/kg/d. On their first sample, 12 patients (43%) had a concentration between 15 and 30 mg/L. On day 1, the median (range) estimated area under the curve was 349 (201–1,001) mg/L × hr, and seven patients (25%) had an area under the curve greater than 400 mg/L × hr. Using the pharmacokinetics model, the median (range) calculated initial daily dose, taking into account age, bodyweight, and serum creatinine concentration, was 53 (36–69) mg/kg/d resulting in a simulated day 1 area under the curve of 409 (341–593) mg/L × h with a theoretical pharmacokinetic target attainment of 57%.

Conclusions:

The current continuous infusion of vancomycin dosing scheme used in our population was inappropriate and led to underexposure. Using pharmacokinetic approaches such as covariate-adjusted initial dosing and Bayesian estimation of exposure should prove useful for achieving the pharmacokinetic target.
Effects of Resistance Training on Fatigue-Related Domains of Quality of Life and Mood During Pregnancy: A Randomized Trial in Pregnant Women With Increased Risk of Back Pain
Authors: O'Connor Patrick J. , Poudevigne Mélanie S. , Johnson Kristen E. , Brito de Araujo Juliana , Ward-Ritacco Christie L.
Published: February 2018

Objective

The aim of the study was to test whether the adoption of twice weekly, low-to-moderate intensity resistance training during weeks 22 to 34 of pregnancy can improve quality of life and mood.

Methods

A parallel-group trial was conducted. Women in their second trimester (N = 134) were randomly assigned to 12 weeks of wait list, bimonthly pregnancy education classes, or twice weekly low-to-moderate intensity resistance training. Resistance training involved one abdominal exercise with no external load and five exercises (leg extension, leg press, arm lat pull, leg curl, and lumbar extension) with an external load that gradually progressed, and the total active exercise time during each exercise session was approximately 17 minutes. Quality of life and mood were measured before and after the interventions using the 36-item Short Form Health Survey and Profile of Mood States. Intent-to-treat mixed-model analyses of variance (3 groups by 2 times, pre- and postintervention) tested the hypothesis that outcomes would worsen for the controls and not change or improve for the resistance training group.

Results

The group by time interaction (F(2,131) = 3.144, η2 = .046, p = .046) for 36-item Short Form Health Survey vitality and subsequent simple main effects showed that scores were unchanged across time after resistance training (−1.8 (14.8)) but significantly decreased for the education (−6.44 (12.69), t = 3.408, df = 44, p = .001) and wait list (−9.11 (14.78), t = 4.135, df = 44, p < .001) groups, whereas posttest vitality scores for the pregnancy group (45.9 (16.9)) were significantly higher than the wait list (40.1 (16.3), t = 1.989, df = 87, p = .05) but not the education group (42.1 (15.4), p = .27). Profile of mood states fatigue scores showed a similar pattern.

Conclusions

Adverse changes in symptoms of energy and fatigue during pregnancy are attenuated by adopting low-to-moderate intensity resistance training.

Clinical Trial Registration

Clinicaltrials.gov, NCT02557893.
Matrine Protects Cardiomyocytes From Ischemia/Reperfusion Injury by Regulating HSP70 Expression Via Activation of the JAK2/STAT3 Pathway
Authors: Guo Suping , Gao Chuanyu , Xiao Wentao , Zhang Jing , Qu Yongsheng , Li Jiang , Ye Famin
Published: February 2018

Studies have shown that matrine showed cardiovascular protective effects; however, its role and mechanism in myocardial ischemia/reperfusion (I/R) injury remain unknown. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway activation and elevated heat shock protein (HSP) 70 are closely related to the prevention of myocardial I/R injury. The cardioprotective effects of matrine were determined in hypoxia/reoxygenation (H/R)-treated primary rat cardiomyocytes and left anterior descending coronary artery ligation and reperfusion animal models. The molecular mechanisms of matrine in myocardial I/R injury were focused on JAK2/STAT3 pathway activation and HSP70 expression. We found that matrine significantly increased H/R-induced the suppression of cell viability, decreased lactate dehydrogenase release, creatine kinase activity, and cardiomyocytes apoptosis in vitro. Moreover, matrine notably reduced the serum levels of creatine kinase-myocardial band (CK-MB) and cardiac troponin I, lessened the infarcted area of the heart, and decreased the apoptotic index of cardiomyocytes induced by I/R in vivo. Matrine activated the JAK2/STAT3 signaling, upregulated HSP70 expression both in vitro and in vivo. The cardioprotective effects of matrine were abrogated by AG490, a JAK2 inhibitor, and HSP70 siRNA. In addition, AG490 reduced HSP70 expression increased by matrine. In conclusion, matrine attenuates myocardial I/R injury by upregulating HSP70 expression via the activation of the JAK2/STAT3 pathway.
Pulmonary Arterial Thrombosis in a Murine Model of Blunt Thoracic Trauma
Authors: Brown Ian E. , Rigor Robert R. , Schutzman Linda M. , Khosravi Nasim , Chung Karen , Becker James A. , Pivetti Christopher D. , Best Gavin T. , Chavez Jessica C. , Galante Joseph M.
Published: February 2018

Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m2). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.
Chlorinated Lipids Elicit Inflammatory Responses in vitro and in vivo
Authors: Yu Hong , Wang Meifang , Wang Derek , Kalogeris Theodore J. , McHowat Jane , Ford David A. , Korthuis Ronald J.
Published: February 2018

Increased endothelial cell adhesion molecule (ECAM) expression, leukocyte-endothelial cell adhesive interactions (LECA), platelet-endothelial cell adhesion (PECA), mast cell activation, production of reactive oxygen species (ROS), and microvascular permeability are hallmarks of the inflammatory response. The infiltration of inflammatory phagocytes is associated with myeloperoxidase (MPO)-dependent production of hypochlorous acid, a reactive chlorinating species that targets membrane lipids to produce halogenated lipids such as 2-chlorohexadecanal (2-ClHDA) and 2-chloropalmitic acid (2-ClPA). Whether these chlorinated lipids contribute to microcirculatory dysfunction is largely unknown. Thus, the objectives of this study were to determine if chlorinated lipids exposure induces such inflammatory responses in an in vitro model employing cultured human intestinal mesenteric vascular endothelial cells (HIMVEC), and in an in vivo model examining responses in small intestinal and mesenteric postcapillary venules of naive rats. Following the addition of either 2-ClPA or 2-ClHDA to the culture medium, HIMVEC displayed increased platelet and neutrophil adherence that was associated with elevated expression of ECAMs and increased permeability. In vivo, chlorinated lipid exposure significantly increased LECA, PECA, ROS production, and albumin leakage, inflammatory events that were associated with mast cell activation and increased tissue MPO activity and expression. Our data provide proof-of-principle that 2-ClPA and 2-ClHDA induce powerful proinflammatory responses both in vitro and in vivo, suggesting the possibility that these chlorinated lipid products of the MPO/ hydrogen peroxide /chloride system may contribute to inflammation noted in neutrophil-dependent, myeloperoxidase-mediated pathologic states such as ischemia/reperfusion, hemorrhagic shock, and sepsis.
Migraine Surgery
Authors: Gfrerer Lisa , Hulsen John H. , McLeod Matthew D. , Wright Eric J. , Austen William G.
Published: February 2018

Objective:

A detailed analysis of outcomes after migraine surgery suggests an anatomic etiology of pain, such as peripheral nerve compression, in select patients.

Background:

Historically, surgeons have not played a role in the treatment of migraine. However, a subgroup of patients with extracranial anatomic triggers appear to benefit from surgical intervention. Traditionally, the determination of success or failure of migraine surgery is based on whether there is greater or less than 50% improvement of the migraine headache index (MHI) after surgery. However, in this study, patients either did not respond to treatment (≤5%) or improved completely (≥80%). Detailed analysis is provided of this surprising finding.

Methods:

Subjects completed a prospective migraine questionnaire preoperatively as well as at 3 and 12 months postoperatively.

Results:

All variables improved significantly from baseline. Interestingly, in 83% of patients, the MHI improved either ≥80% or ≤5%, suggesting a more binary distribution. Only 17% of indices fell in the intermediate (5% to 80%) range. Moreover, 69% of patients had ≥80% improvement resulting in a mean improvement of 96% in this group. The remaining 14% had ≤5% improvement, with an average improvement of 0%.

Conclusion:

Migraine surgery remains controversial. Traditional conservative therapy targets the central theory of migraine propagation. This study again prospectively demonstrates the efficacy of surgical trigger site deactivation in migraine patients. Patients either failed to improve or improved after surgery, with few intermediate outcomes. The binary distribution of data lends further support to an anatomic etiology of pain, that is, peripheral nerve compression, in select patients.
Effects of Navigated Repetitive Transcranial Magnetic Stimulation After Stroke
Authors: Chervyakov Alexander V. , Poydasheva Alexandra G. , Lyukmanov Roman H. , Suponeva Natalia A. , Chernikova Ludmila A. , Piradov Michael A. , Ustinova Ksenia I.
Published: February 2018

Purpose:

The purpose of this study was to test the effects of navigated repetitive transcranial magnetic stimulation, delivered in different modes, on motor impairments and functional limitations after stroke.

Methods:

The study sample included 42 patients (58.5 ± 10.7 years; 26 males) who experienced a single unilateral stroke (1–12 months previously) in the area of the middle cerebral artery. Patients completed a course of conventional rehabilitation, together with 10 sessions of navigated repetitive transcranial magnetic stimulation or sham stimulation. Stimulation was scheduled five times a week over two consecutive weeks in an inpatient clinical setting. Patients were randomly assigned to one of four groups and received sham stimulation (n = 10), low-frequency (1-Hz) stimulation of the nonaffected hemisphere (n = 11), high-frequency (10-Hz) stimulation of the affected hemisphere (n = 13), or sequential combination of low- and high-frequency stimulations (n = 8). Participants were evaluated before and after stimulation with clinical tests, including the arm and hand section of the Fugl–Meyer Assessment Scale, modified Ashworth Scale of Muscle Spasticity, and Barthel Index of Activities of Daily Living.

Results:

Participants in the three groups receiving navigated repetitive transcranial magnetic stimulation showed improvements in arm and hand functions on the Fugl–Meyer Stroke Assessment Scale. Ashworth Scale of Muscle Spasticity and Barthel Index scores were significantly reduced in groups receiving low- or high-frequency stimulation alone.

Conclusions:

Including navigated repetitive transcranial magnetic stimulation in a conventional rehabilitation program positively influenced motor and functional recovery in study participants, demonstrating the clinical potential of the method. The results of this study will be used for designing a large-scale clinical trial.