bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Impairments Associated With Post–Intensive Care Syndrome: Systematic Review Based on the World Health Organization's International Classification of Functioning, Disability and Health Framework
Authors: Ohtake Patricia J , Lee Alan C , Scott Jacqueline Coffey , Hinman Rana S , Ali Naeem A , Hinkson Carl R , Needham Dale M , Shutter Lori , Smith-Gabai Helene , Spires Mary C , Thiele Alecia , Wiencek Clareen , Smith James M
Published: June 2018

Background

Post–intensive care syndrome (PICS) is a constellation of new or worsening impairments in physical, mental, or cognitive abilities or a combination of these in individuals who have survived critical illness requiring intensive care.

Purpose

The 2 purposes of this systematic review were to identify the scope and magnitude of physical problems associated with PICS during the first year after critical illness and to use the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework to elucidate impairments of body functions and structures, activity limitations, and participation restrictions associated with PICS.

Data Sources

Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, CINAHL Plus with Full Text (EBSCO), Web of Science, and Embase were searched from inception until March 7, 2017.

Study Selection

Two reviewers screened titles, abstracts, and full text to independently determine study eligibility based on inclusion and exclusion criteria.

Data Extraction

Study methodological quality was assessed using the Newcastle–Ottawa Scale. Data describing study methods, design, and participant outcomes were extracted.

Data Synthesis

Fifteen studies were eligible for review. Within the first year following critical illness, people who had received intensive care experienced impairments in all 3 domains of the ICF (body functions and structures, activity limitations, and participation restrictions). These impairments included decreased pulmonary function, reduced strength of respiratory and limb muscles, reduced 6-minute walk test distance, reduced ability to perform activities of daily living and instrumental activities of daily living, and reduced ability to return to driving and paid employment.

Limitations

The inclusion of only 15 observational studies in this review may limit the generalizability of the findings.

Conclusions

During the first year following critical illness, individuals with PICS experienced physical impairments in all 3 domains of the ICF.
Visions of Colonial Nairobi: William Simpson, Health, Segregation and the Problems of Ordering a Plural Society, 1907–1921
Authors: Greenwood Anna , Topiwala Harshad
Published: June 2018

The 1915 Simpson Report made public health recommendations for Nairobi that were heralded as ground-breaking. Of particular interest to the colonial authorities was Professor Simpson’s suggestion to racially segregate Nairobi to prevent diseases said to emanate from its Indian bazaar. Rather than being novel, this article shows that these recommendations were typical of enthusiasm for segregation in other parts of Empire, as well as being in line with earlier health reform proposals for Nairobi. Furthermore, although public health justified racially discriminatory practices for European ends, this was not a predictable story of Indians uniting against segregation and Europeans campaigning for it. Indeed, the debates stimulated by Simpson reveal some disunity amongst Kenyan Indians. Additionally, when segregation plans were dropped in 1921 Indians continued to live in their own sub-communities in Nairobi, indicating that opposition to segregation was as much a symbolic political battle than a cultural necessity.
Can Maintenance of Certification Work? Associations of MOC and Improvements in Physicians’ Knowledge and Practice
Authors: Price David W. , Biernacki Helene , Nora Lois Margaret
Published: June 2018

Purpose

To summarize the findings of studies, conducted by individuals both internal and external to the American Board of Medical Specialties (ABMS) Member Boards, of the associations of Maintenance of Certification (MOC) and improvements in physicians’ knowledge and patient care processes or outcomes.

Method

The authors conducted a narrative review of studies identified by searching PubMed and Web of Science for English-language articles from the United States published between 2000 and May 2017. To be included, articles had to examine the relationship of MOC to physician knowledge, clinical practice processes, or patient care outcomes. The initial search yielded 811 articles. After two rounds of review and excluding those articles that did not fit the study criteria, 39 articles were included for analysis.

Results

The 39 included studies were conducted by or included diplomates of 12 ABMS Member Boards. Twenty-two studies examined MOC processes that were developed by an ABMS Board; 17 examined interventions that were developed by nonboard entities but accepted for MOC credit by an ABMS Board. Thirty-eight studies examined a single component of MOC; 24 studied the improvement in medical practice component. Thirty-seven studies reported at least one positive outcome.

Conclusions

Most of the studies included in this review highlighted circumstances in which MOC was associated with positive impacts on physician knowledge and patient care processes or outcomes. Future collaborative research is needed to improve the relevance, helpfulness, and generalizability of continuing certification to different physicians across specialties and practice settings.
Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study
Authors: Schart-Morén Nadine , Agrawal Sumit K. , Ladak Hanif M. , Li Hao , Rask-Andersen Helge
Published: June 2018

Objectives:

The purpose of this study was to evaluate the three-dimensional (3D) anatomy and potential damage to the hook region of the human cochlea following various trajectories at cochlear implantation (CI). The goal was to determine which of the approaches can avoid lesions to the soft tissues, including the basilar membrane and its suspension to the lateral wall. Currently, there is increased emphasis on conservation of inner ear structures, even in nonhearing preservation CI surgery.

Design:

Micro-computed tomography and various CI approaches were made in an archival collection of macerated and freshly fixed human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging was used to reproduce the soft tissues. The 3D anatomy was investigated using bony and soft tissue algorithms, and influences on inner ear structures were examined.

Results:

Micro-computed tomography with 3D rendering demonstrated the topography of the round window (RW) and osseous spiral laminae, while synchrotron imaging allowed reproduction of soft tissues such as the basilar membrane and its suspension around the RW membrane. Anterior cochleostomies and anteroinferior cochleostomies invariably damaged the intracochlear soft tissues while inferior cochleostomies sporadically left inner ear structures unaffected.

Conclusions:

Results suggest that cochleostomy approaches often traumatize the soft tissues at the hook region at CI surgery. For optimal structural preservation, the RW approach is, therefore, recommended.
First Place: A prospective, randomized controlled trial of the impact of written discharge instructions for postoperative opioids on patient pain satisfaction and on minimizing opioid risk exposure in orthopaedic surgery
Authors: Singh Supriya , Clarke Collin , Lawendy Abdel Rehman , Macleod Mark , Sanders David , Tieszer Christina
Published: June 2018

Background:

Prescription opioid misuse is a significant issue with multiple consequences for our patients and society. The purpose of this study was to evaluate the role of a postoperative pain guideline pamphlet on patient pain satisfaction, on number of patients seeking a renewal prescription, and on appropriate disposal of leftover prescription medication.

Methods:

This prospective, randomized controlled trial included patients aged 18 to 65 yr undergoing elective foot and ankle surgery, who were opioid naïve and had no preexisting chronic pain conditions. Patients consenting to participate were divided into low-, medium-, and high-use groups according to anticipated postoperative prescription narcotic usage. Patients in each group were randomized to the control group that received no written discharge instructions, or the intervention group that received written instructions outlining postoperative pain expectations and recommendations for opioid medication usage and disposal. Both groups received equivalent prescriptions targeted to the use group (low, medium, or high). At the 4-week postoperative mark, a telephone interview was conducted to evaluate the primary outcome of pain satisfaction using a modified brief pain inventory. Secondary outcomes included renewal of opioid prescription and disposal method of leftover medication.

Results:

A total of 80 patients were recruited for this study. Of the 80 patients, 22 were classified as low use, 45 moderate use, and 13 high use. There was no difference among group demographics, other than the surgery being performed. Of the 80 patients, 41 received postoperative pain instructions and 39 did not. On average, pain satisfaction postoperatively was 8.19/10, where 10/10 represented completely satisfied. Interference scores averaged 27.18/70. Interestingly, only seven patients (six moderate use and one high use) used the entirety of their prescription, and only five patients required a renewal of their prescription. Only five patients returned their surplus medication to the pharmacy despite 41 patients receiving direct instructions to do so.

Conclusions:

Written discharge instructions in this patient population did not appear to improve postoperative pain scores. Interestingly, this study captured that a small percentage of postoperative pain medication prescriptions are completely utilized. Even more concerning is the fact that very little of the leftover pain medication is disposed of appropriately. Overprescribing narcotic medication may contribute to the issue of opioid abuse, and we should consider our role in minimizing opioid prescriptions postoperatively.
Third Place: MRI safety of external fixation devices: a review of the literature
Authors: Perry Kevin J. , Massey Patrick A. , Simoncini Alberto , Barton R. Shane
Published: June 2018

Orthopaedic trauma patients often require temporary stabilization prior to definitive treatment following the principles of damage control orthopaedics (DCO). DCO includes the use of temporary or supplemental implants including pelvic external fixators, large external fixators, small external fixators, ring external fixators, skeletal traction, cervical traction, and cervical halo fixation. Once provisional stabilization has been obtained, and the patient is optimized medically, further testing can be performed prior to definitive stabilization. Since MRI may be required before definitive fixation, it is necessary to understand MRI safety in patients with external fixation devices.
The orthopaedic burden of cancer care
Authors: Zeitlinger Lauren , Wallace Matthew T. , Frassica Frank J. , Aboulafia Albert J.
Published: June 2018

Cancer treatment and survivorship management continue to be rapidly evolving aspects of modern healthcare systems. As cancer survivorship has changed, the effects of prescribed treatments and their long-term morbidities are beginning to be understood, necessitating awareness by the orthopaedic profession of the diagnostic and management challenges of cancer patients with musculoskeletal complaints. The likelihood that cancer patients and cancer survivors will seek orthopaedic evaluation for a consequence of treatment is reasonably high and likely will to continue to expand. We help outline the consequences of cancer treatment that warrant unique orthopaedic considerations.
Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial
Authors: Mai-Yi Fan Sabrina , Cheng Yu-Pin , Lee Ming-Yung , Lin Sung-Jan , Chiu Hsien-Yi
Published: June 2018

BACKGROUND

Previous studies have reported the benefits of low-level/light laser therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate.

OBJECTIVE

To investigate the efficacy and safety of LLLT on hair regrowth in patients with AGA.

METHODS

This 24-week, randomized, double-blind, self-comparison, sham device-controlled trial enrolled 100 patients with AGA. All participants were randomly assigned to receive the investigational LLLT on one side of the head and sham light treatment on the contralateral side, 3 times weekly for 30 minutes each, over a 24-week period. Global scalp photography, phototrichogram assessment, the investigator's global assessment (IGA) of hair regrowth, and the subject's assessment of the treatment satisfaction were used for evaluation.

RESULTS

After 24 weeks of treatment, the LLLT-treated scalp exhibited significantly greater hair coverage than the sham light-treated side (14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT-treated side than in the sham light-treated side at the 12- and 24-week visits. No serious adverse events were observed.

CONCLUSION

The use of LLLT might be an effective, safe, well-tolerated treatment for AGA.
CHARACTERIZATION OF THE CHOROIDAL VASCULATURE IN MYOPIC MACULOPATHY WITH OPTICAL COHERENCE TOMOGRAPHIC ANGIOGRAPHY
Authors: Wong Chee Wai , Teo Yi Chong Kelvin , Tsai Shih Tsiang Andrew , Ting Shu Wei Daniel , Yeo Yew San Ian , Wong Wen Kuan Doric , Lee Shu Yen , Wong Tien Yin , Cheung Chui Ming Gemmy
Published: June 2018

Purpose:

To characterize the choriocapillaris (CC) in highly myopic eyes with myopic maculopathy, using optical coherence tomographic angiography.

Methods:

Prospective, clinic-based study of 42 eyes of 38 patients with high myopia (≤−6 diopters and axial length ≥26.5 mm). Myopic maculopathy was graded from fundus photographs according to the Meta-Analysis for Pathologic Myopia classification. Macular 3 × 3 mm en face optical coherence tomographic angiographic images were obtained with swept-source optical coherence tomographic angiography and graded for CC flow impairment as follows: 1) intact CC, 2) focal (<1 mm2), and 3) extensive (>1 mm2).

Results:

Of the 42 eyes, 17 (39.5%) had tessellated fundus, 20 (46.5%) had diffuse, and 6 (14.0%) had patchy atrophy. Choriocapillaris flow impairment was observed in all eyes with diffuse and patchy atrophy. Even in eyes with tessellated fundus only, CC signal voids were seen in 3 eyes (17.6%). With increasingly severe myopic maculopathy, the pattern of CC flow impairment changed from predominantly focal to predominantly extensive.

Conclusion:

Choriocapillaris flow impairment was observed in many highly myopic eyes, even in those with mild fundus changes, and worsened with increasing severity of myopic maculopathy. Longitudinal studies are needed to assess whether CC flow impairment predicts the risk of myopic maculopathy progression.
VALIDITY AND EFFICACY OF INTERNAL LIMITING MEMBRANE PEELING DURING INITIAL VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: VISUAL OUTCOMES IN MACULA-SPARING CASES
Authors: Akiyama Kunihiko , Fujinami Kaoru , Watanabe Ken , Fukui Masaki , Tsunoda Kazushige , Noda Toru
Published: June 2018

Purpose:

To compare the visual outcomes and prevalence of epiretinal membrane (ERM) growth postoperatively between eyes treated with and without internal limiting membrane peeling during vitrectomy for macula-sparing rhegmatogenous retinal detachment.

Methods:

Fifty-five consecutive cases who underwent vitrectomy for macula-sparing rhegmatogenous retinal detachment were reviewed retrospectively. The inclusion criteria were a minimal 6-month follow-up postoperatively and spectral domain optical coherence tomographic images available at follow-up. Cases with any pre-existing macular condition possibly affecting the visual prognosis were excluded. All cases were divided into two groups: 22 cases without internal limiting membrane peeling (Group 1) and 33 cases with internal limiting membrane peeling (Group 2). The two groups were compared using the Mann–Whitney U test and Fisher exact test in terms of the best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) before vitrectomy, postoperative BCVA, and the presence of postoperative ERM growth. Postoperative BCVA and ERM growth were determined at 6 months, 12 months, and the last visit. The visual outcomes were also analyzed between cases with and without postoperative symptomatic ERM growth, which caused visual impairment and required surgical removal.

Results:

The mean postoperative BCVAs were 0.00, −0.08, and −0.08 logarithm of the minimum angle of resolution in Group 1, and −0.08, −0.08, and −0.08 logarithm of the minimum angle of resolution in Group 2 at 6 months, 12 months, and the last visit, respectively, and did not differ significantly between the 2 groups at each time point except for at 12 months (P = 0.027). An ERM developed in 14 cases in Group 1, 7 of which were symptomatic. No cases in Group 2 had ERM growth. The prevalence of ERM growth was significantly (P < 0.001) higher in Group 1 than Group 2. The BCVA was significantly worse at 6 months (P = 0.011), 12 months (P = 0.003), and the last visit (P = 0.019) in 7 cases with symptomatic ERMs (median, 0.30, 0.15, and 0.10 logarithm of the minimum angle of resolution, respectively) than in 48 cases without symptomatic ERMs (median, −0.08, −0.08, and −0.08 logarithm of the minimum angle of resolution, respectively).

Conclusion:

Internal limiting membrane peeling did not result in decreased visual acuity postoperatively in cases with a macula-sparing rhegmatogenous retinal detachment, and the procedure significantly prevented postsurgical ERM growth. Symptomatic ERMs led to decreased visual acuity even after surgical removal. These results support the validity and efficacy of internal limiting membrane peeling for preventing ERM growth after rhegmatogenous retinal detachment repair.
Immune Cells on the Donor Corneal Endothelium After Corneal Transplantation
Authors: Okumura Naoki , Inoue Ryota , Nakano Shinichiro , Imai Hirofumi , Matsumoto Daiki , Kayukawa Kanae , Wakimasu Koichi , Kitazawa Koji , Koizumi Noriko , Kinoshita Shigeru
Published: June 2018

Purpose:

The aim of this study was to investigate the existence of presumed immune cells observed by contact specular microscopy in patients who underwent penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:

This cross-sectional study was conducted on consecutive patients who underwent follow-up visits between January and March 2015 for previously performed PK or DSAEK. Presumed immune cell–suspected “cell-like white dots” were evaluated by scanning slit contact specular microscopy. The association between the grading of presumed immune cells with clinical parameters, such as corneal endothelial cell density, time after surgery, and the titer of steroid administration, was also investigated.

Results:

A total of 54 eyes of 54 patients who underwent PK (32 eyes/32 patients) and DSAEK (22 eyes/22 patients) were evaluated, and suspected immune cells were observed in all patients. In the PK and DSAEK groups, the number of patients in the presumed immune cell grades 1, 2, 3, and 4 were 19, 10, 2, and 1 and 10, 8, 2, and 2, respectively (P = 0.663). No statistically significant association was found between the immune cell grades and the clinical parameters.

Conclusions:

Immune cells were observed on the corneal endothelial grafts in all 54 patients who underwent PK or DSAEK. Although the number of immune cells varied between patients and showed no correlation with clinical parameters, it would be beneficial to conduct a future prospective study to analyze the effect of immune cells on postoperative corneal endothelial cell loss.
Familial Risks of Glaucoma in the Population of Sweden
Authors: Li Xinjun , Sundquist Jan , Zöller Bengt , Sundquist Kristina
Published: June 2018

Background:

Glaucoma has a familial component but detailed data on the modification of familial risks are lacking. The aim of the study was to determine detailed familial risks for medically diagnosed glaucoma based on nationwide hospital and population records.

Materials and Methods:

Subjects were obtained from the multigeneration register, contains the Swedish population in families, and glaucoma patients were identified from the hospital discharge register (1987-2012) and the outpatient register (2001-2012). Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected number of cases.

Results:

Familial risks were increased in both male and female individuals. Concordant familial risks were generally higher than discordant risks. For example, familial concordant risks were SIR=3.25 (95% confidence interval, 3.16-3.35) for primary open-angle glaucoma, 9.93 (95% confidence interval, 7.30-13.22) for primary angle-closure glaucoma. Very high familial risks were observed if ≥2 relatives were affected, for example, the high-risk group of multiple affected siblings with an SIR>20. The spouse risk was modestly increased 1.20.

Conclusions and Relevance:

Family history of glaucoma is a strong predictor for glaucoma, and is a potential useful tool in clinical risk assessment. Our data emphasize the contribution of familial factors to the glaucoma.
Orbital, Periorbital, and Intracranial Emphysema Caused by Compressed Air Injury in a 5-Year-Old Child
Authors: Bagheri Abbas , Veisi Amirreza , Memarzade Sayed Ezatollah , Tavakoli Mehdi
Published: June 2018

A 5-year-old boy was accidentally injured by a compressed air blast to his right eye and developed periorbital and subconjunctival emphysema and proptosis subsequently. CT scan showed periorbital subcutaneous and intraorbital emphysema around the right eye, as well as intracranial and cervical emphysema without frank fractures in orbital bones. He was examined under sedation, and the subconjunctival air was aspirated. He was also prophylactically treated with topical and systemic antibiotics to prevent infection. Emphysema was resorbed entirely within 3 weeks. In conclusion, compressed air injury can occur in a child and manifest with orbital and periorbital emphysema without any detectable fracture and any clear entrance site and may need emergent management to save the vision or upper respiratory airways.
Lung Parenchymal and Endobronchial Metastases From Ovarian Carcinoma
Authors: Ayub Irfan I. , Thangaswamy Dhanasekar , Joseph Leena D. , Meenakshisundaram Manickavasagam
Published: June 2018

Ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death in the world with an overall 5-year survival rate of <50%. (1) The most common age of presentation is at the perimenopausal age group and two-thirds of them present with advanced stage of disease. (2) Thoracic metastases occur in up to 50% of patients. Pleural effusion is the most common presentation of thoracic metastases in these patients, whereas pulmonary parenchymal metastases, lymphangitis, and nodal involvement are less commonly reported. (3) Tracheobronchial involvement is rare with few cases reported in literature. Herewith, we are presenting a case of ovarian cancer in a young female with both lung parenchymal and endobronchial metastases. Bronchoscopy revealed endobronchial tumor in right lower lobe bronchus part of which was covered by yellowish necrotic material. Biopsy showed metastatic ovarian malignancy complicated by aspergillosis. She was started on oral itraconazole along with supportive management following which hemoptysis stopped.
Pump Position Impacts HeartMate II Left Ventricular Assist Device Thrombosis
Authors: Kilic Ahmet , Ransom John , Maltais Simon , Sun Benjamin , Entwistle John W. , Bailey Stephen , John Ranjit , Klodell Charles T. , Gregoric Igor , Sheridan Brett , Chuang Joyce , Farrar David J. , Sundareswaran Kartik , Adamson Robert
Published: June 2018

The PREVENtion of HeartMate II pump Thrombosis through clinical management (PREVENT) study was a multicenter, prospective investigation to evaluate the rate of pump thrombosis (PT) with adoption of a uniform set of surgical and medical practices for left ventricular assist device implantation. We sought to quantify pump position at baseline and retrospectively define a pump position associated with poor clinical outcomes. Chest x-rays at baseline were prospectively obtained per protocol. Pump pocket depth, inflow cannula (IC) angle relative to the pump, and IC angle relative to the vertical were measured. Pumps falling in the tail-ends of the IC angle and pump pocket depth distributions were categorized as having an extreme pump position within the PREVENT study. Patients with extreme pump position had a significantly higher risk of confirmed and suspected PT, hemolysis, and elevated lactate dehydrogenase. In a multivariable analysis of survival free of confirmed PT, extreme pump position was an independent risk factor (hazard ratio = 3.6; 95% confidence interval = 1.5–8.9; p = 0.006) when adjusting for differences in pump speed and anticoagulation level. Our analysis shows that HeartMate II pump position at implant can significantly impact event-free survival and the incidence of adverse events at 6 months.
Molecular characterization and sequence analysis of plasmid-mediated quinolone resistance genes in extended-spectrum beta-lactamases producing uropathogenic Escherichia coli in Babylon Province, Iraq
Authors: Al-Hasnawy Huda H. , Jodi Mohammed R. , Hamza Hiba J.
Published: June 2018

The current study was aimed to detect qnrA, qnrB, qnrC, qnrD and qnrS genes in quinolone-resistance extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli isolates that recovered from patients with urinary tract infection in Babylon Province, Iraq. Uropathogenic E. coli (UPEC) was regarded as the most important causative agent of urinary tract infections. Fluoroquinolones are regularly used in the management of these infections; on the other hand, in recent years, an increasing rate of quinolone resistance has been stated globally. Clinical isolates of UPEC were collected from patients with infection of urinary tract and identified by standard laboratory protocols. PCR was used for detection of quinolone resistance genes (qnrA, qnrB, qnrC, qnrD and qnrS) in ESBL-producing isolates, and sequencing of some qnr genes confirmed the results. Out of 208 urine specimens, 42 UPEC isolates of ESBL producing were detected; of them, 27 (64.28%) isolates were found to be resistant to quinolones. PCR results revealed that out of 27 UPEC, five (18.51%) isolates were found to carry both genes qnrS and qnrB, whereas four (14.81%) isolates were harbored qnrD and qnrA, and no isolate was found to have qnrC. Sequencing of qnrB and qnrS genes revealed that mutational changes were observed in qnrB gene; however, no mutational variation was observed in qnrS gene.

The results of the current study revealed the dissemination of ESBL genes in all UPEC isolates that carry the plasmid-mediated qnr genes with low frequency among the clinical isolates and UPEC isolates; these results confirmed that the quinolone resistance in Babylon Province, Iraq might be because of chromosomal genes for this resistance.
The effects of hemorrhage on the pharmacokinetics of tranexamic acid in a swine model
Authors: Derickson Michael J. , McClellan John M. , Marko Shannon T. , Kuckelman John P. , Phillips Cody J. , Barron Morgan R. , Martin Matthew J. , Loughren Michael J.
Published: June 2018

BACKGROUND

The early use of tranexamic acid (TXA) is strongly advocated in patients who are likely to require massive transfusion to decrease mortality. This study determines the influence of hemorrhage on the pharmacokinetics of TXA in a porcine model.

METHODS

The investigation was a prospective experimental study in Yucatan minipigs. First, in vitro plasma-cell partitioning of TXA was evaluated by inoculating whole blood with known aliquots, centrifuging, and measuring the supernatant with high-performance liquid chromatography with mass spectrometry (HPLC-MS). Then, using in vivo modeling, normovolemic and hypovolemic (35% reduction in blood volume) swine (n = 4 per group) received 1 g of intravenous TXA and had blood sampled at 14 time points over 4 hours to determine baseline clearance via HPLC-MS. Additional swine (n = 4) were hemorrhaged 35% of their blood volume, and TXA was administered as a 15 mg/kg infusion over 10 minutes followed by infusion of 1.875 mg/kg per hour to simulate massive hemorrhage scenario. During the first hour of TXA administration, one total blood volume was hemorrhaged and simultaneously replaced with TXA free blood. Serial blood samples and the hemorrhaged blood were analyzed by HPLC-MS to determine the percentage of dose lost via hemorrhage.

RESULTS

Clearance of TXA was diminished in the hypovolemic group compared with the normovolemic group (115 ± 4 vs 70 ± 7 mL/min). Percentage of dose lost via hemorrhage averaged 25%. The lowest measured plasma level during the exchange transfusion was 34 μg/mL.

CONCLUSION

Mean 25% of the present 2017 Joint Trauma System Clinical Practice Guideline dosing of TXA can be lost to hemorrhage if a blood volume is transfused within an hour of initiating therapy. In the case of TXA, which has limited distribution and is administered during active hemorrhage and massive blood transfusions, replacement strategies should be developed and tested to find simple methods of adjusting the current dosing guidelines to maintain therapeutic plasma concentrations.

LEVEL OF EVIDENCE

Therapeutic, level II.
Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation
Authors: Kabagambe Sandra K. , Palma Ivonne P. , Smolin Yulia , Boyer Tristan , Palma Ivania , Sageshima Junichiro , Troppmann Christoph , Santhanakrishnan Chandrasekar , McVicar John P. , Jen Kuang-Yu , Nuño Miriam , Perez Richard V.
Published: June 2018

Background

Despite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation.

Methods

From June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed.

Results

After a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance.

Conclusions

Favorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.
Estimating the distance to an epidemic threshold
Authors: O'Dea Eamon B. , Park Andrew W. , Drake John M.
Published: June 2018

The epidemic threshold of the susceptible–infected–recovered model is a boundary separating parameters that permit epidemics from those that do not. This threshold corresponds to parameters where the system's equilibrium becomes unstable. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here, we show analytically how such slow dynamics can prevent estimation of the distance to the threshold from fluctuations in the susceptible population. Although these results are exact only in the limit of long-term observation of a large system, simulations show that they still provide useful insight into systems with a range of population sizes, environmental noise and observation schemes. Having established some guidelines about when estimates are accurate, we then illustrate how multiple distance estimates can be used to estimate the rate of approach to the threshold. The estimation approach is general and may be applicable to zoonotic pathogens such as Middle East respiratory syndrome-related coronavirus (MERS-CoV) as well as vaccine-preventable diseases like measles.
The effect of alkali-soluble lignin on purified core cellulase and hemicellulase activities during hydrolysis of extractive ammonia-pretreated lignocellulosic biomass
Authors: Zhou Linchao , da Costa Sousa Leonardo , Dale Bruce E. , Feng Jia-Xun , Balan Venkatesh
Published: June 2018

Removing alkali-soluble lignin using extractive ammonia (EA) pretreatment of corn stover (CS) is known to improve biomass conversion efficiency during enzymatic hydrolysis. In this study, we investigated the effect of alkali-soluble lignin on six purified core glycosyl hydrolases and their enzyme synergies, adopting 31 enzyme combinations derived by a five-component simplex centroid model, during EA-CS hydrolysis. Hydrolysis experiment was carried out using EA-CS(−) (approx. 40% lignin removed during EA pretreatment) and EA-CS(+) (where no lignin was extracted). Enzymatic hydrolysis experiments were done at three different enzyme mass loadings (7.5, 15 and 30 mg protein g−1glucan), using a previously developed high-throughput microplate-based protocol, and the sugar yields of glucose and xylose were detected. The optimal enzyme combinations (based on % protein mass loading) of six core glycosyl hydrolases for EA-CS(−) and EA-CS(+) were determined that gave high sugar conversion. The inhibition of lignin on optimal enzyme ratios was studied, by adding fixed amount of alkali-soluble lignin fractions to EA-CS(−), and pure Avicel, beechwood xylan and evaluating their sugar conversion. The optimal enzyme ratios that gave higher sugar conversion for EA-CS(−) were CBH I: 27.2–28.2%, CBH II: 18.2–22.2%, EG I: 29.2–34.3%, EX: 9.0–14.1%, βX: 7.2–10.2%, βG: 1.0–5.0% (at 7.5–30 mg g−1protein mass loading). Endoglucanase was inhibited to a greater extent than other core cellulases and xylanases by lignin during enzyme hydrolysis. We also found that alkali-soluble lignin inhibits cellulase more strongly than hemicellulase during the course of enzyme hydrolysis.
Rapid degradation of malachite green by CoFe
2
O
4
–SiC foam under microwave radiation
Authors: Mao Yanpeng , Yang Shanxiu , Xue Chao , Zhang Miaomiao , Wang Wenlong , Song Zhanlong , Zhao Xiqiang , Sun Jing
Published: June 2018

This study demonstrated rapid degradation of malachite green (MG) by a microwave (MW)-induced enhanced catalytic process with CoFe
2
O
4
–SiC foam. The catalyst was synthesized from CoFe
2
O
4
particles and SiC foam by the hydrothermal method. X-ray diffraction and scanning electron microscopy techniques were used to confirm that CoFe
2
O
4
particles were settled on the surface of SiC foam. In this experiment, a novel fixed-bed reactor was set up with this catalyst for a continuous flow process in a MW oven. The different parameters that affect the MW-induced degradation rate of MG were explored. The MW irradiation leads to the effective catalytic degradation of MG, achieving 95.01% degradation within 5 min at pH 8.5. At the same time, the good stability and applicability of CoFe
2
O
4
–SiC foam for the degradation process were also discussed, as well as the underlying mechanism. In brief, these findings make the CoFe
2
O
4
–SiC foam an excellent catalyst that could be used in practical rapid degradation of MG.
Ceramide-transfer protein-mediated ceramide transfer is a structurally tunable flow-inducing mechanism with structural feed-forward loops
Authors: Giordano Giulia
Published: June 2018

This paper considers two models of ceramide-transfer protein (CERT)-mediated ceramide transfer at the
trans
-Golgi network proposed in the literature,
short distance shuttle
and
neck swinging
, and seeks
structural
(parameter-free) features of the two models, which rely exclusively on the peculiar interaction network and not on specific parameter values. In particular, it is shown that both models can be seen as flow-inducing systems, where the flows between pairs of species are tuned by the concentrations of other species, and suitable external inputs can
structurally
regulate ceramide transfer. In the short distance shuttle model, the amount of transferred ceramide is
structurally
tuned by active protein kinase D (PKD), both directly and indirectly, in a coherent feed-forward loop motif. In the neck-swinging model, the amount of transferred ceramide is
structurally
tuned by active PI4KIIIβ, while active PKD has an ambivalent effect, due to the presence of an incoherent feed-forward loop motif that directly inhibits ceramide transfer and indirectly promotes it; the
structural
role of active PKD is to favour CERT mobility in the cytosol. It is also shown that the influences among key variables often have
structurally
determined steady-state signs, which can help falsify the models against experimental traces.
A damage initiation criterion for a class of viscoelastic solids
Authors: Alagappan P. , Rajagopal K. R. , Kannan K.
Published: June 2018

We extend the methodology introduced for the initiation of damage within the context of a class of elastic solids to a class of viscoelastic solids (Alagappan
et al.
2016
Proc. R. Soc. Lond. A: Math. Phys. Eng. Sci.
472
, 20160231. (
doi:10.1098/rspa.2016.0231
)). In a departure from studies on damage that consider the body to be homogeneous, with initiation of damage being decided by parameters that are based on a quantity such as the strain, that requires information concerning a special reference configuration, or the use of ad hoc parameters that have no physically meaningful origins, in this study we use a physically relevant parameter that is completely determined in the current deformed state of the body to predict the initiation of damage. Damage is initiated due to the inhomogeneity of the body wherein certain regions in the body are unable to withstand the stresses, strains, etc. The specific inhomogeneity that is considered is the variation of the density in the body. We consider damage within the context of the deformation of two representative viscoelastic solids, a generalization of a model proposed by Gent (1996
Rubber Chemistry and Technology
69
, 59–61. (
doi:10.5254/1.3538357
)) for polymeric solids and a generalization of the Kelvin–Voigt model. We find that the criterion leads to results that are in keeping with the experiments of Gent & Lindley (1959
Proc. R. Soc. Lond. A: Math. Phys. Eng. Sci.
249
, 195–205. (
doi:10.1098/rspa.1959.0016
)).
Lower bumblebee colony reproductive success in agricultural compared with urban environments
Authors: Samuelson Ash E. , Gill Richard J. , Brown Mark J. F. , Leadbeater Ellouise
Published: June 2018

Urbanization represents a rapidly growing driver of land-use change. While it is clear that urbanization impacts species abundance and diversity, direct effects of urban land use on animal reproductive success are rarely documented. Here, we show that urban land use is linked to long-term colony reproductive output in a key pollinator. We reared colonies from wild-caught bumblebee (
Bombus terrestris
) queens, placed them at sites characterized by varying degrees of urbanization from inner city to rural farmland and monitored the production of sexual offspring across the entire colony cycle
.
Our land-use cluster analysis identified three site categories, and this categorization was a strong predictor of colony performance. Crucially, colonies in the two clusters characterized by urban development produced more sexual offspring than those in the cluster dominated by agricultural land. These colonies also reached higher peak size, had more food stores, encountered fewer parasite invasions and survived for longer. Our results show a link between urbanization and bumblebee colony reproductive success, supporting the theory that urban areas provide a refuge for pollinator populations in an otherwise barren agricultural landscape.
T cell and peripheral blood parameters define progression of autoimmune disease in the IL-2Rα KO model
Authors: Mullins Genevieve N. , Valentine Kristen M. , Al-Kuhlani Mufadhal , Davini Dan , Jensen Kirk D.C. , Hoyer Katrina K.
Published: June 2018

IL-2Rα is required to generate the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. Mice deficient in IL-2Rα (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18-80 days of age. These mice develop kinetically differing autoimmune disease, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters that distinguish cohorts of mice that develop early- and late-stage autoimmune disease in the IL-2Rα-KO genetic background. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, and hematopoietic progenitor changes, to assess the extent of peripheral autoimmune hemolytic anemia and bone marrow failure. Early onset disease correlated with anti-RBC antibodies and lower hematocrit on day 19. We also found that predicted late stage-disease IL-2Rα-KO mice have higher numbers of developing memory CD4 and CD8 T cells and reduced AIHA at early ages. The expansion of CD8 T cells seen in IL-2R -KO mice is driven by unimpaired IL-2 signaling which correlated with increased IL-2RP expression. Using a simple CBC we were able to predict disease kinetics to explore mechanisms underlying early and late disease.
A histone H4K20 methylation-mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing
Authors: Shoaib Muhammad , Walter David , Gillespie Peter J. , Izard Fanny , Fahrenkrog Birthe , Lleres David , Lerdrup Mads , Johansen Jens Vilstrup , Hansen Klaus , Julien Eric , Blow J. Julian , Sørensen Claus S.
Published: June 2018

The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. The mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here, we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, appropriate chromatin relaxation is safeguarded by SET8-dependent methylation of histone H4 on lysine 20. Thus, in the absence of either SET8 or the H4K20 residue, substantial genome-wide chromatin decompaction occurs which allows excessive loading of the Origin Recognition Complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and the loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase.
Quantification and discovery of sequence determinants of protein per mRNA amount in 29 human tissues
Authors: Eraslan Basak , Wang Dongxue , Gusic Mirjana , Prokisch Holger , Hallström Björn , Uhlen Mathias , Asplund Anna , Ponten Frederik , Wieland Thomas , Hopf Thomas , Hahne Hannes , Kuster Bernhard , Gagneur Julien
Published: June 2018

Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein-to-mRNA (PTR) ratios and a quantification of their effects is still lacking. Here we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We analyzed the contribution of known sequence determinants of protein synthesis and degradation and 15 novel mRNA and protein sequence motifs that we found by association testing. While the dynamic range of PTR ratios spans more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2-fold. A reporter assay provided significant functional support for two novel UTR motifs and a proteome-wide competition-binding assay identified motif-specific bound proteins for one motif. Moreover, our direct comparison of protein to RNA levels led to a new metrics of codon optimality. Altogether, this study shows that a large fraction of PTR ratio variance across genes can be predicted from sequence and identified many new candidate post-transcriptional regulatory elements in the human genome.
Identification of evolutionarily conserved virulence factor by selective pressure analysis ofStreptococcus pneumoniae
Authors: Yamaguchi Masaya , Goto Kana , Hirose Yujiro , Yamaguchi Yuka , Sumitomo Tomoko , Nakata Masanobu , Nakano Kazuhiko , Kawabata Shigetada
Published: June 2018

Evolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins sinceStreptococcus pneumoniaeis one of the pathogen posing the greatest threats to human health. Phylogenetic and molecular analyses revealed thatcbpJhad the highest codon rates to total numbers of codons under significant negative selection among those examined. Ourin vitroandin vivoassays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency ofcbpLunder relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.