bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovation Activities and Integration through Vertical Acquisitions
Authors: Frésard Laurent , Hoberg Gerard , Phillips Gordon M
Published: September 2019

We examine the determinants of vertical acquisitions using product text linked to product vocabulary from input-output tables. We find that the innovation stage is important in understanding vertical integration. R&D-intensive firms are less likely to become targets of vertical acquisitions. In contrast, firms with patented innovation are more likely to sell to vertically related buyers. Firms’ R&D intensity is a more important deterrent to their vertical acquisitions when the provision of innovation incentives by potential acquirers is more difficult. The role of patents in fostering vertical acquisitions is more prevalent when potential buyers face a higher risk of holdup. (JEL G32, G34, L22, L25, O34)
Prevalence and Risk Factors of Allergic Bronchopulmonary Aspergillosis and Aspergillus Sensitization in Children with Poorly Controlled Asthma
Authors: Kumari Jyoti , Jat Kana Ram , Lodha Rakesh , Jana Manisha , Xess Immaculata , Kabra Sushil K
Published: September 2019

Background

Allergic bronchopulmonary aspergillosis (ABPA) may be a risk factor for poorly controlled asthma in children. The studies regarding prevalence and risk factors of ABPA in children with poorly controlled asthma are limited in number.

Objectives

To determine prevalence and risk factors of ABPA and aspergillus sensitization (AS) in children with poorly controlled asthma.

Methods

In this prospective cross-sectional study from a tertiary care center in India, we enrolled asthmatic children 5–15 years of age with poorly controlled asthma. We did the following investigations: spirometry, skin prick test, serum total immunoglobulin E (IgE), aspergillus-specific IgE and immunoglobulin G, serum precipitin for Aspergillus, absolute eosinophil count, chest X-ray and high-resolution computed tomography of the chest. ABPA and AS were diagnosed as per the recently proposed criteria.

Results

We enrolled 106 children [boys 72 (67.9%); mean age of 10.2 ± 2.6 years] with poorly controlled asthma. The prevalence of ABPA and AS were 11.3% (95% CI, 5.2–17.5%) and 61.3% (95% CI, 52.0–70.7%), respectively. The presence of brownish sputum was significantly more in ABPA compared with non-ABPA patients (33.3 vs. 4.2%, p = 0.002). The age, gender, allergic rhinitis and gastroesophageal reflux were not significantly different in ABPA compared with non-ABPA patients.

Conclusion

The prevalence of ABPA and AS was 11.3 and 61.3%, respectively in children with poorly controlled asthma. We could not find any risk factors for ABPA except that the presence of brownish sputum was more in children with ABPA. Spirometry parameters were not significantly different in ABPA compared with non-ABPA patients.
The Relation Between Patients’ Beliefs About Pain Medication, Medication Adherence, and Treatment Outcome in Chronic Pain Patients
Authors: Timmerman Leon , Stronks Dirk L. , Huygen Frank J.
Published: September 2019

Objectives:

Nonadherence to prescribed pain medication is common in chronic noncancer pain patients. Beliefs about pain medication have been reported to be associated with nonadherence behavior in cross-sectional studies. The aim of this study was to prospectively investigate the relationship between patients’ beliefs about pain medication and their medication adherence and treatment outcome.

Methods:

Chronic noncancer pain patients completed a baseline questionnaire including the 47-item Pain Medication Attitudes Questionnaire, consisting of 7 subscales with regards to beliefs on prescribed medication. After 11 weeks, medication underuse and overuse were assessed by self-report. In addition, patient satisfaction with regards to the effect of prescribed pain medication and satisfaction as regards prescribed medication and care, and the burden of side effects were assessed.

Results:

A total of 133 participants completed the baseline questionnaire, and 99 patients completed the follow-up questionnaire. Concerns over side effects at baseline were positively associated with underuse and the presence of side effects after 11 weeks. The perceived need was positively associated with overuse, whereas concerns over addiction were negatively associated with overuse. Concerns over tolerance were negatively associated with patient satisfaction with medication effects after 11 weeks. Concerns over tolerance and mistrust in the prescribing doctor were negatively associated with satisfaction about medication and care.

Conclusion:

Attitudes and concerns toward pain medication are associated with adherence patterns and outcome parameters. To improve medication adherence and therapy outcome, patient beliefs about pain medication should be taken into account by providing tailored education, adequate follow-up, or alternate therapy.
Acute Pain Assessment in Prematurely Born Infants Below 29 Weeks
Authors: Meesters Naomi J. , Simons Sinno H.P. , van Rosmalen Joost , Holsti Liisa , Reiss Irwin K.M. , van Dijk Monique
Published: September 2019

Objectives:

Neonates born extremely prematurely are at high risk of acute and prolonged pain. Effective treatment requires reliable pain assessment, which is currently missing. Our study explored whether existing pain assessment tools and physiological indicators measure pain and comfort accurately in this population.

Materials and Methods:

We prospectively collected data in 16 neonates born at less than 29 weeks’ gestational age during 3 conditions: skin-to-skin care, rest, and heelstick procedure for capillary blood sampling in the incubator. The neonates were video recorded in these situations, and recordings were coded using 5 observational pain assessment tools and numeric rating scales for pain and distress. We simultaneously collected heart rate, respiratory rate, arterial oxygen saturation, regional cerebral oxygenation, and the number of skin conductance peaks. All measures across the 3 conditions were compared using general linear modeling.

Results:

The median gestational age was 27.1 weeks (range: 24.1 to 28.7). Forty measurement periods across the 3 conditions were analyzed. Heart rate was significantly higher during heelstick procedures compared with during rest, with a mean difference of 10.7 beats/min (95% confidence interval [CI]: 2.7-18.6). Oxygen saturation was significantly higher during skin-to-skin care compared with during heelstick procedures with a mean difference of 5.5% (95% CI: 0.2-10.8). The Premature Infant Pain Profile-revised (PIPP-R) score was significantly higher during heelstick procedures compared with skin-to-skin care with a mean difference of 3.2 points (95% CI: 1.6-5.0).

Discussion:

Pain measurement in clinical practice in prematurely born infants below 29 weeks remains challenging. The included behavioral and physiological indicators did not adequately distinguish between a painful situation, rest, and skin-to-skin care in premature neonates.
The Impact of Emotional Regulation Strategies on Pain Catastrophizing in the Context of Interpersonal Relationships
Authors: Leonard Michelle T. , Krajewski-Kidd Katie , Shuler Rickey , Wesolowicz Danielle , Miller Chazlyn , Chatkoff David
Published: September 2019

Objectives:

The Communal Coping Model suggests that pain catastrophizing may serve to elicit support from others. What is not known is how emotional regulation, namely emotional inhibition, impacts pain catastrophizing within the context of an interpersonal relationship. Individuals who have a greater tendency to emotionally inhibit may have a greater likelihood to use catastrophizing as a means for seeking support, particularly in relationships characterized by satisfaction and emotional validation.

Methods:

Data were collected from 50 undergraduate couples at the University of Michigan-Dearborn. Participants were videotaped during the completion of an acute pain cold pressor task and completed measures involving pain catastrophizing, emotional inhibition, and relationship dynamics (ie, Ambivalence Over Emotional Expressiveness Questionnaire, White Bear Suppression Inventory, Dyadic Adjustment Scale). In addition, the videotaped interactions were coded for both invalidation/validation and overt expressions of pain catastrophizing.

Results:

Emotional inhibition, and both validation and invalidation were associated with pain catastrophizing. Observed validation and invalidation were not, however, directly associated with relationship satisfaction. Hierarchical linear regression showed a significant interaction between thought suppression and relationship satisfaction to predict pain catastrophizing.

Discussion:

Results show relationship satisfaction moderates the association between pain catastrophizing and thought suppression in a manner in which couples with high levels of relationship satisfaction who also engage in thought suppression are more likely to use pain catastrophizing as a cognitive strategy to elicit support. This study offers direction into treatment and suggests that couples based cognitive-behavioral treatments that aim to utilize adaptive cognitive and behavioral coping strategies, as well as emotional exploration and validation, may be beneficial.
Initial evaluation by a nonsurgeon provider does not delay the surgical care of operative ankle fractures in a walk-in orthopaedic clinic: A retrospective cohort study
Authors: Fournier Matthew N. , Cline Joseph T. , Seal Adam , Smith Richard A. , Throckmorton Thomas W. , Bettin Clayton C. , Murphy Garnett A.
Published: September 2019

Background:

Orthopaedic walk-in and after-hours clinics may be staffed by orthopaedic surgeons, nonsurgeon physicians, advanced practice nurses, or physician assistants. This study assessed whether initial evaluation by a nonsurgeon delays the care of patients with ankle fractures that require surgery compared to initial evaluation by an orthopaedic surgeon.

Methods:

Patients evaluated in an orthopaedic walk-in clinic who subsequently had surgery for an isolated ankle fracture were identified and were divided based on whether initial evaluation was by an orthopaedic surgeon or a nonsurgeon provider. Patients evaluated and subsequently treated by a fellowship-trained foot and ankle surgeon in his/her private practice served as a control group. Outcome measures included number of clinic visits before surgery, number of providers seen, days until evaluation by a treating surgeon, and days until definitive surgical management.

Results:

Of 138 patients evaluated in a walk-in clinic who subsequently had surgical fixation of an ankle fracture, 61 were seen by an orthopaedic surgeon and 77 by a nonsurgeon provider. No significant differences were found between patients initially evaluated by surgeons and those evaluated by nonsurgeons in days to evaluation by treating surgeon or days until definitive surgical treatment. The average numbers of providers seen and clinic visits before surgery were similar. Patients evaluated and treated only in a single foot and ankle surgeon’s practice had significantly fewer clinic visits and fewer days between evaluation and surgery than the walk-in groups.

Conclusions:

Initial evaluation in a walk-in orthopaedic clinic setting is associated with a longer time between initial evaluation and treatment compared to a single foot and ankle surgeon’s clinic, but this difference may not be clinically significant. Initial evaluation by a nonsurgeon provider is not associated with an increased time to definitive treatment compared to evaluation by an orthopaedic surgeon in a walk-in clinic.

Level of Evidence:

Level III.
Extensive Spinal Fusion Surgery in Patients With Parkinson Disease or Atypical Parkinsonism
Authors: Yamato Yu , Hasegawa Tomohiko , Togawa Daisuke , Yoshida Go , Yasuda Tatsuya , Banno Tomohiro , Oe Shin , Arima Hideyuki , Mihara Yuki , Ushirozako Hiroki , Kobayashi Sho , Matsuyama Yukihiro
Published: September 2019

Study Design.

A retrospective case series.

Objective.

To clarify the mid-term results of extensive spinal fusion surgery in patients with Parkinson disease (PD) or atypical Parkinsonism, especially with respect to their activities of daily living (ADL) over time

Summary of Background Data.

Postural disorders associated with PD lead to spinal imbalance and deformity, resulting in significant disabilities. Clinical outcomes of extensive fusion surgeries in patients with PD over a medium-term follow-up period are currently unknown.

Methods.

Patients with PD who underwent extensive fusion surgery more than 5 years prior were included. The patients’ backgrounds, surgical and radiographic parameters, perioperative and mechanical complications, and indoor ADL over time were assessed. To assess the activities of severely disabled patients, indoor ADL was classified into four stages: independent; or cane, walker, and wheelchair use.

Results.

Twenty-two patients (mean age, 70.6 yrs) were included. The mean blood loss, duration of surgery, and fusion levels were 2039 mL, 424 minutes, and 11.9 levels, respectively. Sagittal vertical axis improved from 220 mm preoperatively to 95 mm postoperatively. Perioperative complications were observed in 17 cases (77%). Before surgery, 1, 5, 12, and four cases were independent in ADL, T-cane, walker, and wheelchair use, respectively, which improved to seven, four, six, and four, respectively in 1 year. Revision surgeries were performed in eight patients (36%) within 3 years of surgery. In the 3 to 5 years after the surgery, the ADL of nine patients worsened due to deterioration of PD. Fifteen cases were followed up over 5 years, at which one, two, four, and seven cases were independent in ADL, cane, walker, and wheelchair use, respectively.

Conclusion.

Surgical intervention in PD patients with spinal deformities leads to good short-term outcomes; however, the patients’ conditions deteriorated because of complications within 3 years and worsening of PD over 3 years after the surgery.

Level of Evidence: 4
The histological microstructure and in vitro mechanical properties of pregnant and postmenopausal ewe perineal body
Authors: Kochová Petra , Hympánová Lucie , Rynkevic Rita , Cimrman Robert , Tonar Zbyněk , Deprest Jan , Kalis Vladimir
Published: September 2019

Objective:

The mechanical properties and microstructure of the perineal body are important for the improvement of numerical models of pelvic organs. We determined the mechanical parameters and volume fractions of the ewe perineal body as an animal model.

Methods:

The 39 specimens of 13 pregnant swifter ewes delivering by cesarean section (aged 2 years, weight 61.2 ± 6.2 kg (mean ± standard deviation) and 24 specimens of 8 postmenopausal swifter ewes 150 days after surgical ovariectomy (aged 7 years, 58.6 ± 4.6 kg)) were loaded uniaxially to determine Young's moduli of elasticity in the small (E0) and large (E1) deformation regions, and ultimate stresses and strains. The 63 adjacent tissue samples were processed histologically to assess volume fractions of smooth and skeletal muscle, adipose cells, elastin, and type I collagen using a stereological point testing grid. We compared the structural and mechanical differences along the ewe perineal body, and between pregnant and postmenopausal groups.

Results:

The pregnant/postmenopausal perineal body was composed of smooth muscle (12/14%; median), skeletal muscle (12/16%), collagen (10/23%), elastin (8/7%), and adipose cells (6/6%). The E0 was 37/11 kPa (median), E1 was 0.97/1.04 MPa, ultimate stress was 0.55/0.59 MPa, and ultimate strain was 0.90/0.87 for pregnant/postmenopausal perineal body. The perineal body showed a structural and mechanical stability across the sites. The pregnant ewes had a higher amount of skeletal muscle, higher E0, and a less amount of collagen when compared with postmenopausal ewes.

Conclusions:

The data can be used as input for models simulating vaginal delivery, pelvic floor prolapsed, or dysfunction.
Histological Corneal Alterations in Keratoconus After Crosslinking—Expansion of Findings
Authors: Müller Philipp L. , Loeffler Karin U. , Messmer Elisabeth , Holz Frank G. , Perdikakis Georgios , Kohlhaas Markus , Herwig-Carl Martina C.
Published: September 2019

Purpose:

To investigate histopathologic, immunohistochemical, and electron microscopic findings in 8 keratoplasty specimens with a history of corneal collagen crosslinking (CXL) for keratoconus. Five new (hitherto unreported) and 3 previously published specimens were analyzed.

Methods:

Corneal buttons of 8 keratoconus corneas (5–114 months after CXL) were compared with 5 keratoconus specimens without CXL and 5 normal corneas for morphological alterations. Corneal buttons were evaluated by light microscopy and immunohistochemistry using antibodies against CD34, PGP 9.5, nestin, telomerase reverse transcriptase, and Ki67 as well as by transmission electron microscopy.

Results:

Keratoconus corneas after CXL showed a significant keratocyte loss (except 1 specimen with an increased keratocyte number), whereas keratoconus corneas without CXL revealed a higher keratocyte density compared with healthy controls. Keratocyte loss could be clinically correlated with corneal opacification and corneal perforation. In corneas after CXL, the remaining keratocytes appeared more polymorphic and revealed a different expression of surface markers similar to keratocytes in corneal scars. The presence of proteoglycans, nerves, and endothelial cells was unaffected by CXL.

Conclusions:

CXL may cause permanent keratocyte loss or repopulation of altered keratocytes, resulting in clinical complications such as corneal opacification or perforation. Despite its good safety profile and high effectiveness in progressive keratoconus, CXL should be performed in accordance with current guidelines strictly adhering to protocol and safety standards.
Programmed Death Ligand 1 Testing of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration Samples Acquired For the Diagnosis and Staging of Non–Small Cell Lung Cancer
Authors: Smith Allister , Wang Hangjun , Zerbo Alix , Beaudoin Stéphane , Ofiara Linda , Fiset Pierre-Olivier , Benedetti Andrea , Gonzalez Anne V.
Published: September 2019

Rationale:

Immunotherapy has become an integral part of management in patients with advanced non–small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression in at least 50% of tumor cells on histologic samples has been correlated with improved efficacy of the immune checkpoint inhibitor pembrolizumab. A limited number of studies have examined the suitability of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) specimens for assessment of PD-L1 status.

Objective:

We sought to examine the feasibility and results of PD-L1 testing performed on EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC.

Materials and Methods:

Patients were identified from a prospectively maintained pathology database. Baseline characteristics were tabulated. Hematoxylin and eosin slides were reviewed to categorize cellularity between <100, 100 to 500, and >500 viable tumor cells. Samples were tested using Dako’s PD-L1 IHC 22C3 pharmDx kit, with a minimum of 100 viable tumor cells. For patients in whom additional tissue samples were available, the results of PD-L1 testing were compared.

Results:

PD-L1 testing was attempted on 120 EBUS-TBNA samples. The most common NSCLC subtype was adenocarcinoma (78%). Seventy-six specimens (63%) had a cellularity >500 tumor cells. Among 110 of 120 (92%) patients with an adequate endobronchial ultrasound (EBUS) sample, 53 of 110 (48.2%) had high PD-L1 expression, defined as a Tumor Proportion Score ≥50%. EBUS PD-L1 results were concordant with an available histologic sample in 14 of 18 patients (78%), with no false-negative results.

Conclusion:

PD-L1 testing was feasible in the majority of EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Comparison of EBUS results with histologic samples revealed moderate concordance, with no false-negative results.
Diphenhydramine Use in End-Stage Kidney Disease
Authors: Nguyen Timothy , Polyakova Beatrice , Cerenzio John , Ramilo Josh Renzo
Published: September 2019

Background:

Diphenhydramine is commonly used in patients with kidney disease and end-stage kidney disease (ESKD) for sleep, allergic reactions, itching, and dialysis treatment related complications, and misuse associated with diphenhydramine is also reported. Diphenhydramine's pharmacokinetics property is reviewed and discussed.

Areas of Uncertainty:

Diphenhydramine is highly bound to albumin. The safety profile and dosing information of diphenhydramine use in ESKD population is lacking. The purpose of this study is to provide an overview of diphenhydramine pharmacokinetic properties and evaluate diphenhydramine use in ESKD population.

Data Sources:

A literature search was conducted during Spring 2019 using PubMed, CINAHL, Cochrane, Ovid, and Google Scholar. Search terms used include “diphenhydramine abuse,” “diphenhydramine dialysis,” and “diphenhydramine kidney disease.”

Results:

There is lack of studies available for diphenhydramine, kidney disease, and dialysis. There were case reports of diphenhydramine abuse and toxicity due to overdose. Diphenhydramine is highly bound to protein that limits its ability to dialyze, and therefore, it may predispose to side effects. Information on diphenhydramine used in the dialysis population is scarce, and dosing toxicity is unknown.

Conclusions:

The data available for use of diphenhydramine in ESKD and dialysis are limited. Clinicians should use caution with the use of diphenhydramine in this population.
Developing, Promoting, and Sustaining Palliative Care Across Central Eastern Europe
Authors: Mitrea Nicoleta , Ancuţa Camelia , Malloy Pamela , Moşoiu Daniela
Published: September 2019

Worldwide, health care is becoming more complex and multifaceted. Nurses, who spend more time at the bedside or out in the community with patients and their families than any other health care professional, need leadership-building skills in order to navigate these challenging times. New guidelines focus on interprofessional and holistic care, emphasizing the importance of building leadership skills and abilities. The World Health Organization and the European Association for Palliative Care have shown interest in influencing the development and implementation of palliative care services globally, given the increasingly aging population, the growing incidence of cancer, and the human immunodeficiency virus/AIDS epidemic. Despite challenges in developing leadership skills in nurses throughout Central and Eastern Europe (CEE), visionary nursing leaders throughout these countries have taken the opportunity to develop the Transformational Palliative Nursing Leadership Program, which has been designed to improve the leadership abilities of palliative care nurses throughout CEE countries. The purpose of the Transformational Palliative Nursing Leadership Program education is to equip palliative care nurses with the ability to promote, develop, and sustain this specialized care in CEE countries or any other part of the world.
Silent Illumination
Authors: Campbell Cathy L. , Catlett Lauren
Published: September 2019

With a growing population of transgender-identified elders in the United States, their unique spiritual end-of-life needs are coming to light. This article presents a case study of a hospice volunteer who used skillful means as an artist to help a transgender-identified woman express her spirituality in the last 6 months of her life. After data analysis, 4 themes emerged related to the expression of spirituality by lesbian, gay, bisexual, transgender, and queer (LGBTQ) elders at end of life. The themes that emerged included (1) the human element in advocacy for spiritual care, (2) the importance of safe spaces for reflection and meditation, (3) the importance of skillful means to work with LGBTQ people, and (4) acknowledgement of gender identity as a spiritual need. This case study serves as a springboard to advance research into the end-of-life needs of LGBTQ elders and the ways in which members of the hospice team can support spiritual care and alleviate suffering for this population.
Brief Report: Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors
Authors: Tan Chen S. , Ghofrani Joshua , Geiger Emma , Koralnik Igor J. , Jost Stephanie
Published: September 2019

Background:

Progressive multifocal leukoencephalopathy (PML) is an often fatal disease caused by JC virus (JCV) in severely immunocompromised patients, including HIV patients. Development of therapeutics to prevent or treat PML is an urgent medical need. While JCV-specific T cells are crucial to control JCV and recover from PML, the role played by antibodies remains unclear. Anti-JCV antibodies, including potent neutralizing antibodies, can be detected in most infected adults, yet in PML patients, JCV seems to escape from neutralization. Whether antibodies can contribute to JCV control by eliciting Fc-mediated effector functions activity has not been evaluated.

Methods:

We measured the capacity of plasma anti-JCV VP1 antibodies to recruit Fc receptor (FcR)-bearing effector cell functions in 28 HIV patients, comparing subjects without PML with PML survivors (PML S) who were alive 1 year after disease onset or PML progressors (PML P) who succumbed within the first year. Antibody titers against JCV VP1 and HIV gp140 trimer were determined by end-point titer dilution ELISA. FcR–mediated natural killer cell degranulation and IFN-γ production were measured as surrogate for in vitro antibody-dependent cellular cytotoxicity (ADCC).

Results:

PML S had higher JCV antibody titers than PML P and patients without PML. However, anti-JCV antibodies had a higher ability to functionally engage FcR in PML P than PML S. Antibody titers and ADCC activity did not vary over time in PML S. Anti-HIV antibody titers and ADCC activity were similar among groups.

Conclusions:

The ability of anti-JCV antibodies to stimulate FcR-bearing effector cell activity might contribute to the outcome of PML. Further studies are warranted to define Fc-mediated functions of anti-JCV antibodies and evaluate whether ADCC can contain JCV replication.
Microbiology of Implant-Based Breast Reconstruction Infections
Authors: Banuelos Joseph , Abu-Ghname Amjed , Asaad Malke , Vyas Krishna , Sohail M. Rizwan , Sharaf Basel
Published: September 2019

Background

Postsurgical complications have been an increasing concern for hospitals, particularly in light of payment reform. The costs to the health care system are increasing in light of Medicare penalties for readmissions for certain conditions. Surgical site infection following implant-based breast reconstruction (IBR) remains challenging. The rates of positive cultures and isolated microorganisms in IBR are unknown. This systematic review summarizes the reported microorganisms and positive culture rates in the existing literature.

Methods

A systematic review was performed using the guidelines outlined in Preferred Reporting Items for Systematic Reviews and Meta-analyses. Articles were included if breast implant infection rates and culture results were reported. Further subgroup analysis of culture positive infections was performed.

Results

A total of 25 studies were included, encompassing 25,177 IBR. Implant infections were reported in 1356 reconstructions (5.4%). Cultures were positive in 74.5% of infections. Gram-positive bacteria were the most common (68.6%), of which Staphylococcus species (51%) was the most isolated pathogen, followed by Pseudomonas. A subgroup analysis showed that early infections (63% vs 88%), radiotherapy (82% vs 93%), and acellular dermal matrix use (90% vs 100%) were associated with lower positive culture rates than their respective counterparts. Patients who received chemotherapy had higher positive culture results (94% vs 83%). Isolated microorganisms also varied among the subgroups.

Conclusions

This systematic review outlines reported microorganisms in IBR. Staphylococcus species and Pseudomonas were the most frequently reported microorganism. Negative cultures were reported in up to 25.5% of infections. Patients with early infections, radiotherapy, and acellular dermal matrix demonstrated higher negative culture rates. This review can help guide the use of empirical antimicrobial therapy in IBR.
Adjustable Fat Repositioning With Intraoral Anchoring
Authors: Gao Wei , Qiao Congzhen , Lin Xiaoxi
Published: September 2019

Background

Prominent tear trough deformity and midfacial depression are the first priority in periorbital rejuvenation. To achieve harmonious lower eyelid improvement, we developed a novel approach to reposition infraorbital fat using intraoral anchoring in transconjunctival lower eyelid blepharoplasty.

Methods

Fourteen patients were included. Blepharoplasty involved infraorbital fat repositioning by intraoral anchoring via a transconjunctival incision to address depression and grooves deformities. Optimal fat repositioning can be achieved by intraorally manipulating suture tension. Photographs were taken both preoperatively and postoperatively. Time of operation, complications, recovery time, and postoperative outcomes were evaluated.

Results

Fourteen patients underwent blepharoplasty between August of 2018 and December of 2018. Their mean age was 36.9 ± 6.1 years. Grooves deformities and depression were eliminated, and the periorbital contour significantly improved. All patients were satisfied with postoperative outcomes. There were no major complications observed.

Conclusions

Intraoral anchoring of the infraorbital fat pedicles yields a significantly improved lower eyelid appearance and requires minimum clinic visits and an extremely short recovery time. In addition, the maneuverable intraoral anchoring allows for customization of patient aesthetics. This approach can be regarded as a true alternative for lower lid rejuvenation, and the outcome is straightforward and predictable.
Triamcinolone Acetonide Suppresses Keloid Formation Through Enhancing Apoptosis in a Nude Mouse Model
Authors: Chen Austin D. , Chen Rong-Fu , Li Yun-Ting , Huang Yu-Ting , Lin Sin-Daw , Lai Chung-Sheng , Kuo Yur-Ren
Published: September 2019

Background

Current understanding of steroid treatments for keloids is in regards to modulation of inflammation, proliferation, and apoptosis, with no in vivo study on the latter. Using a nude mouse model, we investigated whether triamcinolone acetonide (TA) injections induce keloids regression through enhancing apoptosis.

Materials and Methods

Thirty-six keloid specimens (1 × 1 cm) were harvested from 6 patients and separated into sets of 2 from the same patient: no treatment and intralesional TA injection (0.4 mg/mL/kg) at 8 weeks of postimplantation. One set was implanted in each of 18 randomly selected nude mice, which were separated into 3 groups based on time of keloid harvesting after treatment: group A, 2 weeks; group B, 8 weeks; and group C, 14 weeks. Each group had 1 set of specimen from each patient. Histological staining was performed with hematoxylin and eosin stain. Immunohistochemistry staining was performed for human-prolyl 4-hydroxylase (hPH4) and caspase 3 protein, along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

Results

All keloid specimens survived, with no noted overgrowth. Hematoxylin and eosin staining revealed dense extracellular matrix and viable fibroblasts, and hPH4 immunohistochemistry revealed strong expression, demonstrating keloid viability. Caspase 3 protein and TUNEL expressions were significantly increased in the treatment versus control groups, demonstrating that TA injections induced apoptosis.

Conclusions

Triamcinolone acetonide intralesional injections significantly increased apoptosis in keloids, represented by increased caspase 3 protein and TUNEL expressions, supporting that steroids suppress keloids in part owing to enhancement of apoptosis.
Pharmacokinetics, Pharmacodynamics, and Safety of Nivolumab in Patients With Sepsis-Induced Immunosuppression: A Multicenter, Open-Label Phase 1/2 Study
Authors: Watanabe Eizo , Nishida Osamu , Kakihana Yasuyuki , Odani Motoi , Okamura Tatsuaki , Harada Tomohiro , Oda Shigeto
Published: September 2019

Background:

Sepsis often induces an immunosuppressive state, which is associated with high mortality rates. Immunostimulation may be beneficial for sepsis. We investigated the pharmacokinetics, pharmacodynamics, and safety of nivolumab, a human programmed death-1 immune checkpoint inhibitor approved for the treatment of several cancers.

Methods:

In this multicenter, open-label phase 1/2 study, a single 480 or 960 mg nivolumab dose was intravenously infused into Japanese patients with immunosuppressive sepsis. Doses were selected to mimic the exposure achieved with the approved dosage for cancer patients (3 mg/kg every 2 weeks [Q2W]).

Results:

Single 480 and 960 mg nivolumab doses were intravenously infused into five and eight patients, respectively. The maximum concentration after 480 mg (132 μg/mL) was similar to the predicted concentration at the end of infusion with 3 mg/kg Q2W (117 μg/mL). The concentration on Day 28 after 960 mg (33.1 μg/mL) was within the predicted trough concentration range for 3 mg/kg Q2W (90% prediction interval 19.0–163 μg/mL). Absolute lymphocyte counts and monocyte human leukocyte antigen-DR subtype expression levels appeared to increase over time. The incidences of adverse events (AEs) were 80% and 50% in the 480 mg and 960 mg groups, respectively. Drug-related AEs were observed in only one patient in the 480 mg group. No deaths related to nivolumab occurred.

Conclusions:

A single dose of 960 mg nivolumab appeared to be well tolerated and sufficient to maintain nivolumab blood concentrations. Both 480 mg and 960 mg nivolumab seemed to improve immune system indices over time.

Trial registration:

JAPIC, JapicCTI-173600.
Early Axonal Injury and Delayed Cytotoxic Cerebral Edema are Associated with Microglial Activation in a Mouse Model of Sepsis
Authors: Pang Diana , Wu Yijen L. , Alcamo Alicia M. , Cummings Jessica , Di Caro Valentina , Walko Thomas , Hsue Victor , Clark Robert S. B. , Panigrahy Ashok , Kochanek Patrick M. , Aneja Rajesh K.
Published: September 2019

Sepsis-induced brain injury is associated with an acute deterioration of mental status resulting in cognitive impairment and acquisition of new functional limitations in sepsis survivors. However, the exact nature of brain injury in this setting is often subtle and remains to be fully characterized both in preclinical studies and at the bedside. Given the translation potential for the use of magnetic resonance imaging (MRI) to define sepsis-induced brain injury, we sought to determine and correlate the cellular changes with neuroradiographic presentations in a classic murine model of sepsis induced by cecal ligation and puncture (CLP). Sepsis was induced in 6–10-week-old male C57/BL6 mice by CLP. We used immunohistochemistry (IHC) to define neuropathology in a mouse model of sepsis along with parallel studies using MRI, focusing on cerebral edema, blood–brain barrier (BBB) disruption, and microglial activation on days 1 and 4 days after CLP. We demonstrate that septic mice had evidence of early axonal injury, inflammation, and robust microglial activation on day 1 followed by cytotoxic edema on day 4 in the cortex, thalamus, and hippocampus in the absence of BBB disruption. We note the superiority of the MRI to detect subtle brain injury and cytotoxic cerebral edema in comparison with the traditional gold standard assessment, i.e., percent brain water (wet-dry weight method). We conclude that inflammatory changes in the septic brain can be detected in real time, and further studies are needed to understand axonal injury and the impact of inhibition of microglial activation on the development of cerebral edema.
Toileting Disability in Older People Residing in Long-term Care or Assisted Living Facilities
Authors: Yeung Jasper , Jones Allyson , Jhangri Gian S. , Gibson William , Hunter Kathleen F. , Wagg Adrian
Published: September 2019

For purposes of this review, we defined toileting disability as a result of practices, procedures, or conditions that result in an individual requiring assistance using the bathroom. This scoping review synthesizes existing knowledge of extrinsic and/or intrinsic factors that might lead to or be associated with toileting disability and identified knowledge gaps related to toileting disability in older adults residing in long-term care or assisted living facilities. A search of 9 electronic databases and the gray literature identified 3613 articles. After exclusions and screening of the full text of 71 articles, 7 remaining eligible articles mapped research activity and identified knowledge gaps in this area. Only 1 study used toileting disability as the primary outcome; it was present in 15% of older adults without dementia living in long term-care facilities (a subgroup that comprised 34% of all residents). The other 6 articles examined factors and treatment of overall activities of daily living (ADL) performance as their primary outcome; in these, toileting disability was added to other difficulties, yielding a summary ADL outcome score. No study reported the incidence, distribution, or factors that affect toileting disability in long-term care; findings of this scoping review suggest a rich research agenda for future investigation.
Risk of a feedback loop between climatic warming and human mobility
Authors: Obradovich Nick , Rahwan Iyad
Published: September 2019

Human behaviours alter—and are altered by—climate. Might the impacts of warming on human behaviours amplify anthropogenic contributions to climate change? Here, we show that warmer temperatures substantially increase transportation use in the USA. To do so, we combine meteorological data with data on vehicle miles travelled (VMT) and public transit trips (PTT) between 2002 and 2018. Moving from freezing temperatures up to 30°C increases VMT by over 10% and amplifies use of public transit by nearly 15%. Temperatures beyond 30°C exert little influence on either outcome. We then examine climate model projections to highlight the possible transportation impacts of future climatic changes. We project that warming over the coming century may add over one trillion cumulative VMT and six billion PTT in the USA alone, presenting the risk of a novel feedback loop in the human–environmental system.
From chemical soup to computing circuit: transforming a contiguous chemical medium into a logic gate network by modulating its external conditions
Authors: Egbert Matthew , Gagnon Jean-Sébastien , Pérez-Mercader Juan
Published: September 2019

It has been shown that it is possible to transform a well-stirred chemical medium into a logic gate simply by varying the chemistry’s external conditions (feed rates, lighting conditions, etc.). We extend this work, showing that the same method can be generalized to spatially extended systems. We vary the external conditions of a well-known chemical medium (a cubic autocatalytic reaction–diffusion model), so that different regions of the simulated chemistry are operating under particular conditions at particular times. In so doing, we are able to transform the initially uniform chemistry, not just into a single logic gate, but into a functionally integrated network of diverse logic gates that operate as a basic computational circuit known as a full-adder.
Within-host mathematical modelling of the incubation period ofSalmonellaTyphi
Authors: Awofisayo-Okuyelu Adedoyin , Pratt Adrian , McCarthy Noel , Hall Ian
Published: September 2019

Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology ofSalmonellaTyphi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases.
Tuning of ion-release capability from bio-ceramic-polymer composites for enhancing cellular activity
Authors: Osada Naoki , Terada Arisa , Maeda Hirotaka , Obata Akiko , Nishikawa Yasutoshi , Kasuga Toshihiro
Published: September 2019

In our previous study, we investigated the synergetic effects of inorganic ions, such as silicate, Mg
2+
and Ca
2+
ions on the osteoblast-like cell behaviour. Mg
2+
ions play an important role in cell adhesion. In the present study, we designed a new composite that releases a high concentration of Mg
2+
ions during the early stage of the bone-forming process, and silicate and Ca
2+
ions continuously throughout this process. Here, 40SiO
2
–40MgO–20Na
2
O glass (G) with high solubility and vaterite-based calcium carbonate (V) were selected as the source of silicate and Mg
2+
and Ca
2+
ions, respectively. These particles were mixed with poly(lactic-
co
-glycolic acid) (PLGA) using a kneading method at 110°C to prepare the composite (G-V/PLGA, G/V/PLGA = 4/56/40 (in weight ratio)). Most of the Mg
2+
ions were released within 3 days of immersion at an important stage for cell adhesion, and silicate and Ca
2+
ions were released continuously at rates of 70–80 and 180 ppm d
−1
, respectively, throughout the experiment (until day 7). Mouse-derived osteoblast-like MC3T3-E1 proliferated more vigorously on G-V/PLGA in comparison with V-containing PLGA without G particles; it is possible to control the ion-release behaviour by incorporating a small amount of glass particles.
Understanding resource driven female–female competition: ovary and liver size in sand gobies
Authors: García-Berro Aurora , Yliportimo Johanna , Lindström Kai , Kvarnemo Charlotta
Published: September 2019

The operational sex ratio (OSR, ready-to-mate males to females) is a key factor determining mating competition. A shortage of a resource essential for reproduction of one sex can affect OSR and lead to competition within the opposite sex for resource-holding mates. In the sand goby (
Pomatoschistus minutus
), a fish with paternal care, male readiness to mate depends on acquiring a nest-site, whereas food abundance primarily impacts female egg production. Comparing body condition and gonadal investment of fish from two populations with different availability in resources (Baltic Sea: few nest-sites, more food; North Sea: many nest-sites, less food), we predicted females carrying more mature eggs in the Baltic Sea than in the North Sea. As predicted, ovaries were larger in Baltic Sea females, and so was the liver (storage of energy reserves and vitellogenic compounds) for both sexes, but particularly for females. More females were judged (based on roundness scores) to be ready to spawn in the Baltic Sea. Together with a nest colonization experiment confirming a previously documented difference between the two areas in nest-site availability, these results indicate a more female-biased OSR in the Baltic Sea population, compared to the North Sea, and generates a prediction that female–female competition for mating opportunities is stronger in the Baltic population. To our knowledge, this is the first time that female reproductive investment is discussed in relation to OSR using field data.
Adsorption behaviour and mechanism of the PFOS substitute OBS (sodium
p
-perfluorous nonenoxybenzene sulfonate) on activated carbon
Authors: Wang Wei , Mi Xin , Shi Huilan , Zhang Xue , Zhou Ziming , Li Chunli , Zhu Donghai
Published: September 2019

Perfluorooctane sulfonate (PFOS) was listed as a persistent organic pollutant by the Stockholm Convention. As a typical alternative to PFOS, sodium
p
-perfluorous nonenoxybenzene sulfonate (OBS) has recently been detected in the aquatic environment which has caused great concern. For the first time, the adsorption behaviour and mechanism of OBS on activated carbon (AC) with different physical and chemical properties were investigated. Decreasing the particle size of AC can accelerate its adsorption for OBS, while AC with too small particle size was not conducive to its adsorption capacity due to the destruction of its pore structure during the mechanical crushing process. Intra-particle diffusion had a lesser effect on the adsorption rate of AC with smaller particle size, higher hydrophilicity and larger pore size. Reactivation of AC by KOH can greatly enlarge their pore size and surface area, greatly increasing their adsorption capacities. The adsorption capacity of two kinds of R-GAC exceeded 0.35 mmol g
−1
, significantly higher than that of other ACs. However, increasing the hydrophilicity of AC would decrease their adsorption capacities. Further investigation indicated that a larger pore size and smaller particle size can greatly enhance the adsorptive removal of OBS on AC in systems with other coexisting PFASs and organic matter due to the reduction of the pore-blocking effect. The spent AC can be successfully regenerated by methanol, and it can be partly regenerated by hot water and NaOH solution. The percentage of regeneration for the spent AC was 70.4% with 90°C water temperature and up to 95% when 5% NaOH was added into the regeneration solution. These findings are very important for developing efficient adsorbents for the removal of these newly emerging PFASs from wastewater and understanding their interfacial behaviour.
A potential for higher-order phenomenological strain gradient plasticity to predict reliable response under non-proportional loading
Authors: Panteghini Andrea , Bardella Lorenzo , Niordson Christian F.
Published: September 2019

We propose a plastic potential for higher-order (HO) phenomenological strain gradient plasticity (SGP), predicting reliable size-dependent response for general loading histories. By constructing the free energy density as a sum of quadratic plastic strain gradient contributions that each transitions into linear terms at different threshold values, we show that we can predict the expected micron-scale behaviour, including increase of strain hardening and strengthening-like behaviour with diminishing size. Furthermore, the anomalous behaviour predicted by most HO theories under non-proportional loading is avoided. Though we demonstrate our findings on the basis of Gurtin (Gurtin 2004
J. Mech. Phys. Solids
52
, 2545–2568,
doi:10.1016/j.jmps.2003.11.002
) distortion gradient plasticity, adopting Nye's dislocation density tensor as primal HO variable, we expect our results to hold qualitatively for any HO SGP theory, including crystal plasticity.