bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bioengineered Cardiac Left Ventricle
Authors: Patel Nikita M. , Birla Ravi K.
Published: September 2017

Left ventricle and aortic valve underdevelopment are presentations in the congenital cardiac condition hypoplastic left heart syndrome (HLHS); current clinical treatments involve right ventricle refunctionalization. Cardiac organoid models provide simplified open chambers engineered into a flow loop, to ameliorate ventricle-type function. Complete bioengineered ventricle development presents a significant advancement in cardiac organoids. This study provides the foundation for bioengineered complete ventricle (BECV) fabrication. Bioengineered trileaflet valve (BETV) molds and chitosan scaffolds were developed to emulate human neonate aortic valve geometry. Bioengineered complete ventricle were fabricated by fitting BETV into a bioengineered open ventricle (BEOV); the chamber was cellularized using a two-stage cellularization strategy, and BETV were passively seeded with rat neonatal cardiac fibroblasts and perfusion cultured for 3 days. Average pressure generated ranged from 0.06 to 0.12 mm Hg; average biopotential output was 1.02 mV. Histologic assessment displayed syncytial-type cardiomyocyte aggregates at the BECV chamber surface; BETV displayed randomly oriented, diffusely distributed cardiac fibroblasts. The fabrication of this novel BECV may aid in developing a functional engineered left ventricle for clinical application in HLHS.
Every‐other‐day Dosing of Oral Viscous Budesonide Is not Effective in the Management of Eosinophlic Esophagitis
Authors: Rubinstein Eitan , Hait Elizabeth E. , Mitchell Paul D. , Lee John J.
Published: September 2017

Background:

Eosinophilic esophagitis (EoE) is a clinicopathologic disorder characterized histologically by esophageal eosinophilia. Oral viscous budesonide (OVB) is an effective treatment with remission rates reported between 55% and 87%; however, topical corticosteroids are associated with increased risk of candidal esophagitis and adrenal suppression. Attempts to decrease the daily dose of topical steroids have resulted in disease relapse. The objective of this study was to determine whether or not reducing the frequency of OVB administration would be effective in controlling esophageal eosinophilia in children and adolescents.

Methods:

Data were obtained by retrospective chart review of patients at Boston Children's Hospital diagnosed with EoE, based on endoscopic findings of >15 eosinophils per high power field (eos/HPF) on esophageal biopsies while on acid blockade. Patients with histologic evidence of response (<15 eos/HPF) while on daily OVB had been offered the option of maintenance therapy based on a Monday‐Wednesday‐Friday (MWF) dosing regimen. Changes in peak esophageal eosinophil counts over time were examined.

Results:

Eight male patients ages 5 to 18 years attained clinical response while receiving daily OVB and were subsequently maintained on a MWF OVB dosing regimen for 3 to 7 months. All 8 patients showed an increase in peak esophageal eosinophils, with 7 of 8 (88%) experiencing disease relapse. In fact, the distribution of peak esophageal eosinophils after MWF dosing was not statistically different from peak levels at diagnosis (P = 0.95).

Conclusions:

An MWF dosing regimen of OVB was not effective at maintaining histologic response in children and adolescents with EoE. Larger prospective studies are warranted to confirm these results.
Prospective Study of Gastrointestinal Symptoms in School Children of South America
Authors: Saps Miguel , Velasco‐Benitez Carlos A. , Blom Puck J.J. , Benninga Marc A. , Nichols‐Vinueza Diana X.
Published: September 2017

Objectives:

The aim of the study was to establish the prevalence of abdominal pain (AP) in school children in Pasto (Colombia) and determine the effect of AP on their daily activities; and compare the prevalence of AP and other gastrointestinal symptoms between school children from Pasto and Chicago.

Methods:

Fourth‐ and fifth‐grade students from a public school and a private school in Colombia were invited to participate in a prospective study using the same methods and questionnaires (Spanish version) as a previous study conducted in Chicago schools. Children completed weekly confidential surveys for 8 consecutive weeks.

Results:

A total of 332 children participated in the study (40% girls, mean age 9.97 years, median 10, range 8–12 years): public school (288), private school (44). A total of 2425 surveys were analyzed. Out of 2656 possible weekly surveys (332 children × 8 weeks), 91.3% were completed. Overall weekly prevalence of gastrointestinal symptoms: AP (39%), nausea (29.5%), constipation (14%), diarrhea (10.5%), vomiting (9%). Children with AP reported interference with activities: gym (21.9%), school (17.3%), difficulty sleeping (13.7%), and social activities (12.6%). Out of all children, 8.4% sought medical attention for AP during the study period.

Conclusions:

Gastrointestinal symptoms are common in school‐aged children in Colombia and interfere with both daily activities and school attendance. The prevalence of AP, diarrhea, and vomiting found in the present study was similar to published prevalence of American children using similar methods.
Ethical Considerations on Disclosure When Medical Error Is Discovered During Medicolegal Death Investigation
Authors: Wolf Dwayne A. , Drake Stacy A. , Snow Francine K.
Published: September 2017

In the course of fulfilling their statutory role, physicians performing medicolegal investigations may recognize clinical colleagues' medical errors. If the error is found to have led directly to the patient's death (missed diagnosis or incorrect diagnosis, for example), then the forensic pathologist has a professional responsibility to include the information in the autopsy report and make sure that the family is appropriately informed. When the error is significant but did not lead directly to the patient's demise, ethical questions may arise regarding the obligations of the medical examiner to disclose the error to the clinicians or to the family. This case depicts the discovery of medical error likely unrelated to the cause of death and describes one possible ethical approach to disclosure derived from an ethical reasoning model addressing ethical principles of respect for persons/autonomy, beneficence, nonmaleficence, and justice.
68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Metastasizing Epithelioid Hemangioendothelioma
Authors: Derlin Thorsten , Hueper Katja , Soudah Bisharah
Published: September 2017

Epithelioid hemangioendothelioma (EHE) is a rare tumor originating from vascular endothelial or pre-endothelial cells. It has the potential to metastasize. We present the case of a 51-year-old woman with metastasizing EHE who underwent both 18F-FDG and 68Ga-DOTA-TATE PET/CT for staging of disease and for evaluation of targeted radionuclide therapy potential. On 68Ga-DOTA-TATE PET scans, intense tracer accumulation was observed in metastases. Besides the increased glucose metabolism in EHE, this case highlights the potential of 68Ga-DOTA-TATE PET/CT for restaging of EHE and the option of targeted radionuclide therapy in this entity.
Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors
Authors: Ballal Sanjana , Yadav Madhav P. , Damle Nishikant A. , Sahoo Ranjit K. , Bal Chandrasekhar
Published: September 2017

Purpose

The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors.

Methods

One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline 68Ga-DOTANOC PET/CT scans. 177Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with 177Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively.

Results

There was no significant difference in the hemoglobin levels after 177Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/μL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression.

Conclusions

Addition of capecitabine therapy with 177Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.
Quality and Safety in Health Care, Part XXXII
Authors: Harolds Jay A.
Published: September 2017

Mortality 12 months after a transcatheter aortic valve replacement (TAVR) is partly due to a number of reasons in addition to the usual preprocedural medical patient risk factors. In patients who need a permanent pacemaker placed after the procedure, the mortality risk goes up. The death rate following a TAVR varies considerably at different institutions, and the past death rate of TAVR patients at an institution is predictive of the mortality rate of new patients having this procedure. In addition, the quality of life of the individual before the procedure is predictive of the 12-month mortality outcome after the TAVR is done.
Diagnostic Challenge of Staging Metastatic Bone Disease in the Morbidly Obese Patients
Authors: Usmani Sharjeel , Marafi Fahad , Ahmed Najeeb , Esmail Abdulredha , Al Kandari Fareeda , Van den Wyngaert Tim
Published: September 2017

Purpose

Optimizing diagnostic imaging may be challenging in obese patients. The quality of conventional bone scintigraphy can be poor in the morbidly obese due to a combination of factors including high background soft tissue activity. In comparison, sodium fluoride (18F-NaF PET-CT) has a better target-to-background ratio attributed to rapid single-pass extraction and fast clearance from the soft tissues. The aim of the present study is to assess the diagnostic efficacy of 18F-NaF PET-CT in the evaluation of bone metastases in obese cancer patients.

Patients and Methods

Two hundred twelve morbidly obese patients (body mass index, 45 ± 5.1 kg/m2; mean age, 57 years; range, 32–81 years) with body mass index greater than 40 kg/m2 referred for NaF PET-CT for osseous staging of malignancy were retrospectively analyzed. All patients underwent PET-CT scan by injecting 2.2 MBq/kg (0.06 mCi/kg) of 18F-NaF.

Results

18F-NaF PET-CT was definitely benign in 145, possibly benign in 3, equivocal in 4, possibly malignant in 13, and definitely malignant in 47 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-NaF PET-CT were 93.1%, 96.1%, 90%, 97.3%, and 95.2%, respectively (95% confidence interval).

Conclusions

The results of the present study indicate that 18F-NaF PET-CT retains its high diagnostic accuracy in morbidly obese patients and, by inference, can be a preferred functional modality in these patients.
Detection of Non–FDG-Avid Residual Sinonasal Malignant Melanoma in the Skull Base With 11C-Choline PET and Contrast-Enhanced MRI
Authors: Qin Chunxia , Hu Fan , Arnous Maher Mohamad Rajab , Lan Xiaoli
Published: September 2017

Primary sinonasal melanoma is a rare disease. We present a case of melanoma in sinuses without abnormal 18F-FDG activity anywhere in the scanned portion of the body. In further assessment, 11C-choline PET/CT revealed high activity in the paranasal sinuses, skull base, and adjacent brain, in agreement with the high signal on contrast-enhanced T1-weighted MRI scan, which suggested the residual tumor.
Mean Platelet Volume, Red Cell Distribution Width, and Neutrophil-to-Lymphocyte Ratio Before and After Surgery in Patients With Carotid Body Tumors
Authors: Bozan Nazim , Kocak Ömer Faruk , Dinc Mehmet Emre , Demir Canser Yilmaz , Turan Mahfuz , Kiroglu Ahmet Faruk
Published: September 2017

Objective:

Carotid body tumors (CBTs) are rare hypervascular benign tumors that originate from the paraganglia at the carotid bifurcation. The red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and mean platelet volume (MPV) may serve as markers in inflammatory, cardiovascular, and neoplastic diseases. However, their prognostic value in CBTs is unknown. The purpose of this study was to assess the leukocyte count, MPV, RDW, and NLR before and after surgery in patients with CBTs.

Methods:

This retrospective trial included data from 80 patients with CBTs and 65 age-matched healthy controls. The leukocyte, neutrophil, lymphocyte and platelet counts, RDW, and MPV were extracted and NLR was calculated from the complete blood count results of participants.

Results:

The leukocyte and neutrophil counts as well as RDW levels were significantly increased in patients with CBTs compared with healthy controls (P = 0.005, P = 0.003, and P = 0.026; respectively). Patients with CBTs had lower lymphocytes counts (P = 0.241) and higher NLRs (P = 0.054); however, the difference was statistically insignificant. Moreover, no statistically significant difference was detected between groups in terms of platelet counts and MPV levels. Furthermore, the leukocyte count, platelet numbers, MPV, RDW, and NLR levels in patients with CBTs were not statistically significant after surgery (all; P > 0.05).

Conclusion:

This is the first study that documents the increased RDW levels and leukocyte count in patients with CBTs. The combined use of RDW and the leukocyte count along with other clinical assessments can be used as a biomarker for CBTs. Further clinical trials with larger cases series are required to determine the actual predictive roles of these systemic biomarkers.
Dislocated Dental Prothesis Sitting at the Larynx in an Aphasic Patient: Potentially Fatal Situation
Authors: Türk Bilge , Ünsal Özlem , Kaya Kerem Sami , Coşkun Berna Uslu
Published: September 2017

Introduction:

Foreign body in respiration tract is a life-threatening emergency and requires urgent treatment. The diagnosis and treatment requires awareness and suspicion of signs and symptoms of foreign body aspiration.

Case:

A unique case of total dental prothesis aspiration of a 44-year-old aphasic patient is presented. The prothesis is completely removed from the larynx.

Discussion:

Foreign-body aspiration is frequently suspected in children, it is rarely thought about in adults with subacute or chronic respiratory symptoms unless an evident history of an aspiration event is obtained. Facial trauma, dental procedures, central nervous system dysfunction due to stroke, mental retardation, metabolic encephalopathy, seizures, and alcoholism are precipitating factors in adults. Careful clinical history and physical examination is mandatory. Foreign bodies located in the laryngeal region are almost always treated with surgery.

Conclusion:

Loose dentures must be avoided especially in mental retarded, aphasic patients, and patients with central nervous system dysfunction.
Postoperative Orthognathic Surgery Edema Assessment With and Without Manual Lymphatic Drainage
Authors: Yaedú Renato Yassutaka Faria , Mello Marina de Almeida Barbosa , Tucunduva Rosana Adami , da Silveira Juliana Specian Zabotini , Takahashi Marina Prado Monson Santana , Valente Ana Carolina Bonetti
Published: September 2017

Objective:

To evaluate the effects of manual lymphatic drainage (MLD) on facial edema and pain in patients who underwent orthognathic surgery from patient and professional perspectives and clinical measures.

Methods:

It is a randomized double-blind clinical trial, where 30 patients who underwent bimaxillary orthognathic surgery were divided into 2 groups (treatment and placebo). One group (treatment) received MLD from 2nd postoperative day, besides cryotherapy and postoperative medications. The other group (placebo) received cryotherapy, medications, and manual superficial sliding movements as placebo. For edema evaluation, facial measurements with tape and photographs were used. To evaluate patients’ perception, visual analog scale for pain and edema was used. In statistical analysis, quantitative data were analyzed using Student t test for normally distributed variables and Mann–Whitney test for non-normal to find differences between groups; 5% significance level was adopted.

Results:

No difference was found between groups in the amount of maximum developed edema (P = 0.290) nor on what day the edema peak occurred (P = 0.091). However, it was found that treatment group showed faster and greater regression of swelling compared with placebo (P < 0.001). Manual lymphatic drainage was not effective in relieving pain in these patients and nor in edema perception (P = 0.784 and P = 0.946, respectively).

Conclusion:

Manual lymphatic drainage was effective in reducing facial measurements in orthognathic surgery postoperatory. When considering patient's pain and swelling perception, no difference was found between groups.
Protection of the Temporomandibular Joint During Syndromic Mandibular Distraction With a Novel Condylar Offloading Device
Authors: Mehta Sagar T. , Moores Neal , Yamashiro Duane , Siddiqi Faizi , Gociman Barbu
Published: September 2017

Mandibular distraction for severe micrognathia in syndromic patients often leads to temporomandibular joint (TMJ) ankylosis, which requires further interventions to regain joint motion. The increased incidence of postdistraction ankylosis is likely related to increased prevalence of preoperative joint pathology in syndromic micrognathic patients. Previous studies have demonstrated that offloading the pressure on the condyle during the distraction process can prevent such TMJ pathology. In this article, the authors describe a successful new method for offloading the condyle to prevent postdistraction ankylosis using an external TMJ offloading device.
Reconstruction of Orbital Floor With Auricular Concha
Authors: Seven Ergin , Tellioglu Ali Teoman , Inozu Emre , Ozakpinar Hulda Rifat , Horoz Ugur , Eryilmaz Avni Tolga , Karamursel Sebat
Published: September 2017

Orbital floor fractures of varying sizes commonly occur after orbital injuries and remain a serious challenge. Serious complications of such fractures include enopthalmos, restriction of extraocular movement, and diplopia. There is a dearth of literature that can be applied widely, easily, and successfully in all such situations, and therefore there is no consensus on the treatment protocol of this pathology yet. Autogenous grafts and alloplastic and allogenic materials with a wide variety of advantages and disadvantages have been discussed. The value of preoperative and postoperative ophthalmological examination should be standard of care in all orbital fracture patients. An ideal reconstructed orbital floor fracture should accelerate the restoration of orbital function with acceptable cosmetic results. Management parameters of orbital fractures such as timing of surgery, incision type, and implant materials, though widely discussed, remain controversial. In this study, 55 patients with orbital floor fractures surgically reconstructed with conchal cartilage grafts between 2008 and 2014 were retrospectively evaluated. Complications and long-time follow-up visit results have been reported with clinical and radiographic findings. The aim of this study was to present the authors’ clinical experiences of reconstruction of blow-out fractures with auricular conchal graft and to evaluate the other materials available for use.
Intraoperative Neurophysiologic Monitoring for Prediction of Postoperative Neurological Improvement in a Child With Chiari Type I Malformation
Authors: Kawasaki Yukari , Uchida Susumu , Onishi Kouhei , Toyokuni Masako , Okanari Kazuo , Fujiki Minoru
Published: September 2017

Introduction:

Although many surgical treatment strategies for Chiari malformation type I (CM-I) have been reported, the most appropriate surgical technique remains controversial. It is wholly ascribable to the complicacy of pathological condition in CM-I. Recently, intraoperative neurophysiologic monitoring (INM) is becoming prevalent in spinal surgery. Indeed, motor-evoked potentials (MEPs) monitoring and somatosensory-evoked potentials (SSEPs) monitoring are standard tools to minimize the risk of neurologic injury and postoperative deficits. The most recent study suggested that multimodality INM can be beneficial in foramen magnum decompression surgery for CM-I patients for surgical positioning and planning. Various authors have investigated the consistency of intraoperative evoked potential changes that might aid the surgeon to determine the appropriate extent of decompression required for an individual patient.

Patient Description:

The authors report the case of a 7-year-old boy who had the signs of medullary and cerebellar dysfunction, clumsy hands, and ataxic gait. He underwent a surgery of foramen magnum decompression with tonsillectomy and duraplasty for CM-I with cervicomedullary compression. His intraoperative MEPs improved (indicated increased-amplitude and shortened-latency) both after craniotomy and durotomy, whereas SSEPs improved only after durotomy. Those results were correlated well with a functional improvement that was apparent in the immediate postoperative hospitalization.

Conclusions:

The authors’ data provides 1 possible interpretation of INM for safety aspect, but also which degree of decompression in each patient will require. The improvement in MEPs and SSEPs observed during decompression procedure may be a good indicator for the prediction of the clinical improvement seen postoperatively.
Olfactory Dysfunction Associated With Neuro-Behçet Disease
Authors: Doğan Remzi , Ertaş Burak , Özücer Berke , Birday Erkingul , Özturan Orhan , Veyseller Bayram
Published: September 2017

Introduction:

Neurologic involvement associated with Behçet disease (BD) is defined as a different entity: Neuro-Behçet disease (NBD). Behçet disease presents with olfactory dysfunction. It is not known whether this is the consequence of mucosal involvement or neurologic involvement.

Objective:

The aim of this study was to investigate whether olfactory dysfunction was further aggravated as the result of neurologic involvement.

Methods:

Sixteen patients diagnosed with NBD and 16 healthy control patients with similar demographic characteristics were recruited as the healthy control group. Expanded Disability Status Scale (EDSS) scoring was used for quantification of neurological disability. All diagnoses were confirmed and categorized with magnetic resonance imaging studies in all patients individually: parenchymal or nonparenchymal. A well-established test of orthonasal olfaction developed at the CCCRC was used. Correlation analysis was carried out.

Results:

The mean CCCRC score of NBD patients was 4.60 out of 7, and this group was diagnosed to be moderately hyposmic, whereas the average score of the control group was 6.5; the difference was significant (P < 0.0001). CCCRC scores of NBD patients were significantly lower compared both healthy control patients and those of BD patients reported in the literature. Mean EDSS score of NBD patients was 1.75 ± 1.0 out of 10 (0—no neurologic disability and 10—worst neurologic disability). Magnetic resonance imaging of NBD patients revealed 4 nonparenchymal and 12 parenchymal patients. Neuro-Behçet disease patients with parenchymal involvement presented with (worse) EDSS scores. Mean olfactory CCCRC score of this group was 4.38 whereas the average olfactory score of the vascular group was 5.25 out 7. Average EDSS score of vascular group was 0.75, much better compared to higher average neurologic disability score of 2.08 for the parenchymal group. Significant correlation existed between the duration of NBD and both olfactory and neurologic dysfunction scores.

Conclusion:

Neuro-Behçet disease present with aggravated olfactory dysfunction compared to BD. Neurologic involvement—especially parenchymal involvement—seems to deteriorate the olfactory dysfunction. Duration of disease is correlated with this severity of dysfunction.
Early chemoprophylaxis is associated with decreased venous thromboembolism risk without concomitant increase in intraspinal hematoma expansion after traumatic spinal cord injury
Authors: Chang Ronald , Scerbo Michelle H. , Schmitt Karl M. , Adams Sasha D. , Choi Timothy J. , Wade Charles E. , Holcomb John B.
Published: September 2017

BACKGROUND

After traumatic spinal cord injury (SCI), there is increased risk of venous thromboembolism (VTE), but chemoprophylaxis (PPX) may cause expansion of intraspinal hematoma (ISH).

METHODS

Single-center retrospective study of adult trauma patients from 2012 to 2015 with SCI. Exclusion criteria: VTE diagnosis, death, or discharge within 48 hours. Patients were dichotomized based on early (≤48 hours) heparinoid and/or aspirin PPX. Intraspinal hematoma expansion was diagnosed intraoperatively or by follow-up radiology. We used multivariable Cox proportional hazards to estimate the effect of PPX on risk of VTE and ISH expansion controlling for age, injury severity score (ISS), complete SCI, and mechanism as static covariates and operative spine procedure as a time-varying covariate.

RESULTS

Five hundred one patients with SCI were dichotomized into early PPX (n = 260 [52%]) and no early PPX (n = 241 [48%]). Early PPX patients were less likely blunt injured (91% vs 97%) and had fewer operative spine interventions (65% vs 80%), but age (median, 43 vs 49 years), ISS (median 24 vs 21), admission ISH (47% vs 44%), and VTE (5% vs 9%) were similar. Cox analysis found that early heparinoids was associated with reduced VTE (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16–0.84) and reduced pulmonary embolism (PE) (HR, 0.20; 95% CI, 0.06–0.69). The estimated number needed to treat with heparinoids was 10 to prevent one VTE and 13 to prevent one PE at 30 days. Early aspirin was not associated with reduced VTE or PE. Seven patients (1%) had ISH expansion, of which four were on PPX at the time of expansion. Using heparinoid and aspirin as time-varying covariates, neither heparinoids (HR, 1.90; 95% CI, 0.32–11.41) nor aspirin (HR, 3.67; 95% CI, 0.64–20.88) was associated with ISH expansion.

CONCLUSION

Early heparinoid therapy was associated with decreased VTE and PE risk in SCI patients without concomitant increase in ISH expansion.

LEVEL OF EVIDENCE

Therapeutic, level IV.
The prevalence of chronic deep venous thrombosis in trauma: Implications for hospitals and patients
Authors: Cannon Kathleen A. , Badiee Jayraan , Wallace James D. , Brill Jason B. , Sise Michael J. , Bansal Vishal , Sise C. Beth , Shackford Steven R.
Published: September 2017

INTRODUCTION

Deep venous thrombosis (DVT) is considered a preventable complication in trauma patients. Hospitals risk financial penalties for DVT rates above accepted benchmarks. These penalties do not apply to chronic DVT, which develops before admission. Lower-extremity duplex ultrasound (LEDUS) can detect characteristics of thrombus chronicity, allowing differentiation of chronic from acute DVT. The objective of this study was to determine the prevalence of chronic DVT in hospitalized trauma patients.

METHODS

We performed a retrospective review of trauma patients admitted to our Level I trauma center between July 1, 2006 and October 31, 2016 who had a DVT on initial screening LEDUS. Our center utilizes screening and surveillance LEDUS for patients admitted more than 48 hours. Definitions for chronic and acute DVT were extracted from existing literature. Patients with DVT on initial LEDUS underwent review of that LEDUS to assess clot chronicity and were classified as having acute DVT, chronic DVT, or DVT of indeterminate age. Demographic data, medical history, and injury characteristics were collected. Patients with acute DVT and those with chronic DVT were compared.

RESULTS

The prevalence of chronic DVT among patients with a DVT on initial LEDUS was 29.9%. Chronic DVT occurred in patients who were older and less severely injured. An above-knee component was significantly more common in chronic DVT (65%). Only 34 (41%) of those with chronic DVT reported a history of DVT. Among the patients with chronic DVT, 44 (53%) had a subsequent LEDUS, of whom 4 (9%) showed thrombus progression and 6 (14%) formed a new DVT.

CONCLUSION

Lower-extremity duplex ultrasound can identify chronic DVT, which represents nearly 30% of all DVT found on initial screening LEDUS in trauma patients. Those with chronic DVT should receive pharmacologic and mechanical prophylaxis because of the incidence of progression and new acute DVT. They should also be counseled regarding the possibilities of recurrence and chronic venous insufficiency.

LEVEL OF EVIDENCE

Diagnostic study, level III.
Lessons Learned: Recommendations for Establishing Critical Periodic Scientific Benchmarking
Authors: Capella-Gutierrez Salvador , Iglesia Diana de la , Haas Juergen , Lourenco Analia , Fernández José María , Repchevsky Dmitry , Dessimoz Christophe , Schwede Torsten , Notredame Cedric , Gelpi Josep Ll , Valencia Alfonso
Published: September 2017

The dependence of life scientists on software has steadily grown in recent years. For many tasks, researchers have to decide which of the available bioinformatics software are more suitable for their specific needs. Additionally researchers should be able to objectively select the software that provides the highest accuracy, the best efficiency and the highest level of reproducibility when integrated in their research projects.

Critical benchmarking of bioinformatics methods, tools and web services is therefore an essential community service, as well as a critical component of reproducibility efforts. Unbiased and objective evaluations are challenging to set up and can only be effective when built and implemented around community driven efforts, as demonstrated by the many ongoing community challenges in bioinformatics that followed the success of CASP. Community challenges bring the combined benefits of intense collaboration, transparency and standard harmonization. Only open systems for the continuous evaluation of methods offer a perfect complement to community challenges, offering to larger communities of users that could extend far beyond the community of developers, a window to the developments status that they can use for their specific projects. We understand by continuous evaluation systems as those services which are always available and periodically update their data and/or metrics according to a predefined schedule keeping in mind that the performance has to be always seen in terms of each research domain.

We argue here that technology is now mature to bring community driven benchmarking efforts to a higher level that should allow effective interoperability of benchmarks across related methods. New technological developments allow overcoming the limitations of the first experiences on online benchmarking e.g. EVA. We therefore describe OpenEBench, a novel infra-structure designed to establish a continuous automated benchmarking system for bioinformatics methods, tools and web services.

OpenEBench is being developed so as to cater for the needs of the bioinformatics community, especially software developers who need an objective and quantitative way to inform their decisions as well as the larger community of end-users, in their search for unbiased and up-to-date evaluation of bioinformatics methods. As such OpenEBench should soon become a central place for bioinformatics software developers, community-driven benchmarking initiatives, researchers using bioinformatics methods, and funders interested in the result of methods evaluation.
Gene expression drives the evolution of dominance
Authors: Huber Christian D. , Durvasula Arun , Hancock Angela M. , Lohmueller Kirk E.
Published: September 2017

Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance has yet to be quantified in natural populations. Here, we leverage multiple mating systems in natural populations ofArabidopsisto co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arose as the inevitable consequence of the functional importance of genes and their optimal expression levels.

One sentence summary

We use population genomic data to characterize the degree of dominance for new mutations and develop a new theory for its evolution.
Comparison of single genome and allele frequency data reveals discordant demographic histories
Authors: Beichman Annabel C. , Phung Tanya N. , Lohmueller Kirk E.
Published: September 2017

Inference of demographic history from genetic data is a primary goal of population genetics of model and non-model organisms. Whole genome-based approaches such as the Pairwise/Multiple Sequentially Markovian Coalescent (PSMC/MSMC) methods use genomic data from one to four individuals to infer the demographic history of an entire population, while site frequency spectrum (SFS)-based methods use the distribution of allele frequencies in a sample to reconstruct the same historical events. Although both methods are extensively used in empirical studies and perform well on data simulated under simple models, there have been only limited comparisons of them in more complex and realistic settings. Here we use published demographic models based on data from three human populations (Yoruba (YRI), descendants of northwest-Europeans (CEU), and Han Chinese (CHB)) as an empirical test case to study the behavior of both inference procedures. We find that several of the demographic histories inferred by the whole genome-based methods do not predict the genome-wide distribution of heterozygosity nor do they predict the empirical SFS. However, using simulated data, we also find that the whole genome methods can reconstruct the complex demographic models inferred by SFS-based methods, suggesting that the discordant patterns of genetic variation are not attributable to a lack of statistical power, but may reflect unmodeled complexities in the underlying demography. More generally, our findings indicate that demographic inference from a small number of genomes, routine in genomic studies of nonmodel organisms, should be interpreted cautiously, as these models cannot recapitulate other summaries of the data.
Functional characterization and discovery of modulators of SbMATE, the agronomically important aluminium tolerance transporter fromSorghum bicolor
Authors: Doshi Rupak , McGrath Aaron P. , Piñeros Miguel , Szewczyk Paul , Garza Denisse M. , Kochian Leon V. , Chang Geoffrey
Published: September 2017

About 50% of the world’s arable land is strongly acidic (soil pH < 5). The low pH of these soils solubilizes root-toxic ionic aluminium (Al3+) species from clay minerals, driving the evolution of various counteractive adaptations in cultivated crops. The food cropSorghum bicolor, for example, upregulates the membrane-embedded transporter protein SbMATE in its roots. SbMATE mediates efflux of the anionic form of the organic acid, citrate, into the soil rhizosphere, chelating Al3+ions and thereby imparting Al-resistance based on excluding Al+3from the growing root tip. Here, we use electrophysiological, radiolabeled, and fluorescence-based transport assays in two heterologous expression systems to establish a broad substrate recognition profile of SbMATE, showing the transport of14C- citrate anion, as well as the organic monovalent cation, ethidium, but not the divalent ethidium-derivative, propidium. The transport cycle is proton and/or sodium-driven, and shares certain molecular mechanisms with bacterial MATE-family transporters. We further complement our transport assays by directly measuring substrate binding to detergent-purified SbMATE protein. Finally, we use the functionally-folded, purified membrane protein as an antigen to discover high-affinity, native conformation-binding and transport function-altering nanobodies using an animal-free, mRNA/cDNA display technology. Our results demonstrate the utility of usingPichia pastorisas an efficient eukaryotic host to express large quantities of functional plant transporter proteins forin vitrocharacterization. The nanobody discovery approach is applicable to other low immunogenic plant proteins.
Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcalin vivobiofilm formation and necrotizing fasciitis
Authors: Vajjala Anuradha , Biswas Debabrata , Long Chong Kelvin Kian , Tay Wei Hong , Hanski Emanuel , Kline Kimberly A
Published: September 2017

Group AStreptococcus(GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotizing fasciitis (NF). However, mostin vitromodels used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulatein vivoconditions and the host-pathogen interactions that might influence biofilm formation. Here we establish and characterize anin vitromodel of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a murine model of human NF. We show that on mammalian cells, GAS forms dense aggregates that display hallmark biofilm characteristics including a three-dimensional architecture and enhanced tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS) resulting in the release of a host-associated biofilm promoting-factor(s). Supernatants from GAS-infected mammalian cells or from cells treated with endoplasmic reticulum (ER) stressors restore biofilm formation to an SLO and SLS null mutant that is otherwise attenuated in biofilm formation on cells, together suggesting a role for streptolysin-induced ER stress in this process. In an in vivomouse model, the streptolysin-null mutant is attenuated in both microcolony formation and bacterial spread, but pre-treatment of softtissue with an ER-stressor restores the ability of the mutant to form wild type like microcolonies that disseminate throughout the soft tissue. Taken together, we have identified a new role of streptolysin-driven ER stress in GAS biofilm formation and NF disease progression.

Significance Statement

Although it is well-accepted that bacterial biofilms are associated with many chronic infections, little is known about the mechanisms by which group AStreptococcus(GAS) biofilms contribute to acute soft tissue-invasive diseases like necrotizing fasciitis (NF). In this study, we establish a physiologically relevantin vitromodel to study GAS biofilm formation on mammalian cells and validate our findings in a mouse model that mimics human NF. This study demonstrates a novel role of GAS streptolysin-mediated ER stress in the development and spread of GAS biofilms in acute softtissue infections. We also show that biofilm formation depends on the release of a host-associated factor that promotes microcolony formation and GAS disseminationin vivo.
Conserving amphibians in the face of land development: integrating field experiments as a planning tool
Authors: Felson Alexander J.
Published: September 2017

Regulations designed to guide development practices inadequately reflect ecological understanding and fall short of preserving viable habitats. Environmental consultants use rapid assessments and monitoring on individual ponds to rank pond habitat quality, relying on coarse proxies, including vegetative indicators, soil characteristics, hydroperiod, and breeding evidence in obligate species. Planners incorporate these rankings to inform the layout of neighborhoods, roadways, infrastructure and housing. However, important drivers of amphibian survival and fecundity—including metapopulation dynamics, habitat connectivity, watershed health, terrestrial density dependence, and environmental gradients—are often poorly measured and regulated. Given that development proceeds regardless, what options exists improve land development practices?

Integrating experimentation into the planning process can inform land development and improve amphibian conservation. Working as part of the design team we employed an adaptive approach calleddesigned experimentto inform development practices. We manipulatedAmbystoma opacumlarvae within enclosures to test the effects of inter-pond conditions (versus intra-pond density dependence) on the survival and fecundity of conspecifics,Rana sylvatica and Ambystoma maculatum. While the A. maculatum populations were decimated with only 1.5 % survival. ForA. opacumandR. sylvaticaresults indicate habitat variation between ponds accounted for 63.7% and 50.3% of the variance in survival rates of larvae, respectively, and are not predicted by the presence and abundance of egg masses, while density effects accounted for 3.5% and 2.8% of the variation in survival. The results suggest that ponds ranked as high value based on egg mass counts may actually function as habitat sinks. This study illustrates the potential value of assessment approaches that emphasize habitat quality across pond clusters to guide mitigation, conservation, regulations, and to establish sites and funding for ecological research.
Metabolite Extraction from Saccharomyces cerevisiae for Liquid Chromatography–Mass Spectrometry
Authors: Rosebrock Adam P. , Caudy Amy A.
Published: September 2017

Prior to mass spectrometric analysis, cellular small molecules must be extracted and separated from interfering components such as salts and culture medium. To ensure minimal perturbation of metabolism, yeast cells grown in liquid culture are rapidly harvested by filtration as described here. Simultaneous quenching of metabolism and extraction is afforded by immediate immersion in low-temperature organic solvent. Samples prepared using this method are suitable for a range of downstream liquid chromatography–mass spectrometry analyses and are stable in solvent for >1 yr at −80°C.
A High-Throughput Method for the Quantitative Determination of Free Amino Acids in Saccharomyces cerevisiae by Hydrophilic Interaction Chromatography–Tandem Mass Spectrometry
Authors: Mülleder Michael , Bluemlein Katharina , Ralser Markus
Published: September 2017

Amino acids are the building blocks for protein synthesis and the precursors for many biomolecules, such as glutathione and S-adenosylmethionine. Their intracellular concentrations provide valuable information about the overall metabolic state of the cell, as they are closely connected to carbon and nitrogen metabolism and are tightly regulated to meet cellular demands in ever-changing environments. Here, we describe a fast and simple method enabling metabolic profiling for free amino acids for large numbers of yeast strains. Metabolites are extracted with boiling ethanol and, without further conditioning, analyzed by hydrophilic interaction chromatography–tandem mass spectrometry (HILIC-MS/MS). Several hundred samples can be prepared in a single day with an analytical runtime of 3.25 min. This method is valuable for functional characterization, identification of metabolic regulators and processes, or monitoring of biotechnological processes.
Cell Proliferation Analysis during Xenopus Metamorphosis: Using 5-Ethynyl-2-Deoxyuridine (EdU) to Stain Proliferating Intestinal Cells
Authors: Okada Morihiro , Shi Yun-Bo
Published: September 2017

Proper cell proliferation is important for organ homeostasis and normal tissue development. Aberrations in cell proliferation, however, can give rise to degenerative diseases and cancer. Therefore, accurate and simple methods to evaluate cell proliferation are important and necessary to understand the pathways regulating cell proliferation and mechanisms underlying normal development and pathogenesis. The thymidine analog 5-ethynyl-2′-deoxyuridine (EdU), which is incorporated into DNA during active DNA synthesis (e.g., during S phase of the cell cycle), allows easy visualization of proliferating cells. Incorporated EdU can be detected without harsh chemical or enzymatic treatments and is fully compatible with a number of other staining methods, such as immunohistochemistry and in situ hybridization. This protocol describes how to detect proliferating cells using EdU staining in the intestines of Xenopus tadpoles (stages 54–66). Although this method was developed for studying intestinal metamorphosis, it should be applicable to other tissues/organs and other developmental stages as well.
Analysis of Schizosaccharomyces pombe Meiosis
Authors: Yamashita Akira , Sakuno Takeshi , Watanabe Yoshinori , Yamamoto Masayuki
Published: September 2017

Meiosis is a specialized cell cycle that generates haploid gametes from diploid cells. The fission yeast Schizosaccharomyces pombe is one of the best model organisms for studying the regulatory mechanisms of meiosis. S. pombe cells, which normally grow in the haploid state, diploidize by conjugation and initiate meiosis when starved for nutrients, especially nitrogen. Following two rounds of chromosome segregation, spore formation takes place. The switch from mitosis to meiosis is controlled by a kinase, Pat1, and an RNA-binding protein, Mei2. Mei2 is also a key factor for meiosis-specific gene expression. Studies on S. pombe have offered insights into cell cycle regulation and chromosome segregation during meiosis. Here we outline the current understanding of the molecular mechanisms regulating the initiation and progression of meiosis, and introduce methods for the study of meiosis in fission yeast.
Start-to-end simulation of single-particle imaging using ultra-short pulses at the European X-ray Free-Electron Laser
Authors: Fortmann-Grote Carsten , Buzmakov Alexey , Jurek Zoltan , Loh Ne-Te Duane , Samoylova Liubov , Santra Robin , Schneidmiller Evgeny A. , Tschentscher Thomas , Yakubov Sergey , Yoon Chun Hong , Yurkov Michael V. , Ziaja-Motyka Beata , Mancuso Adrian P.
Published: September 2017

Single-particle imaging with X-ray free-electron lasers (XFELs) has the potential to provide structural information at atomic resolution for non-crystalline biomolecules. This potential exists because ultra-short intense pulses can produce interpretable diffraction data notwithstanding radiation damage. This paper explores the impact of pulse duration on the interpretability of diffraction data using comprehensive and realistic simulations of an imaging experiment at the European X-ray Free-Electron Laser. It is found that the optimal pulse duration for molecules with a few thousand atoms at 5 keV lies between 3 and 9 fs.