The effects of supplemental dietary chitosan on broiler performance and myopathic features of white striping.

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate cook loss, drip loss, histopathology scores, and the gene expression of CCR7, LECT2, CD36, PPARG, and PTGS2. There were no significant differences between the broiler weights, thus chitosan did not appear to compromise the overall growth of the broilers. Female broilers fed 0.4% chitosan had the lowest WS incidence, while male broiler fed 0.4% chitosan had the least cook loss. However, gene expression analyses did not offer insight into any grossly or histologically visualized differences in the muscles. Thus, while we can postulate that chitosan could have some positive effect in reducing WS incidence and improving meat quality, further studies are required to better scrutinize the mechanisms by which chitosan affects WS and other such myopathies in fast-growing broilers.

Validation of a Natural Language Machine Learning Model for Safety Literature Surveillance.

INTRODUCTION: As part of routine safety surveillance, thousands of articles of potential interest are manually triaged for review by safety surveillance teams. This manual triage task is an interesting candidate for automation based on the abundance of process data available for training, the performance of natural language processing algorithms for this type of cognitive task, and the small number of safety signals that originate from literature review, resulting in its lower risk profile. However, deep learning algorithms introduce unique risks and the validation of such models for use in Good Pharmacovigilance Practice remains an open question. OBJECTIVE: Qualifying an automated, deep learning approach to literature surveillance for use at AstraZeneca. METHODS: The study is a prospective validation of a literature surveillance triage model, comparing its real-world performance with that of human surveillance teams working in parallel. The biggest risk in modifying this triage process is missing a safety signal (resulting in model false negatives) and hence model recall is the main evaluation metric considered. RESULTS: The model demonstrates consistent global performance from training through testing, with recall rates comparable to that of existing surveillance teams. The model is accepted for use specifically for those products where non-inferiority to the manual process is rigorously demonstrated. CONCLUSION: Characterizing model performance prospectively, under real-world conditions, allows us to thoroughly examine model consistency and failure modes, qualifying it for use in our surveillance processes. We also identify potential future improvements and recognize the opportunity for the community to collaborate on this shared task.

Creation of 21st century anatomy facilities: designing facilities for integrated preclinical education in the Middle East.

BACKGROUND: The establishment of new anatomy facilities needs to accommodate a combination of modern teaching modalities that best align with evidence-based best teaching practices. This article describes the process in which our state-of-the-art anatomy laboratories were designed and implemented, and how these facilities support aspects of modern anatomy education. METHODS: A list of best practices for anatomy education in a modern medical curriculum was summarized from the literature. To assess student satisfaction, a survey related to student perception of the anatomy facilities (5-point Likert scale) was conducted. RESULTS: Our educational modalities include a broad range of teaching approaches. The Instructional Studio houses prosected and plastinated specimens, and cadaveric dissections are performed. Each of our three Dry Laboratories allow for active learning and interaction between small student groups. The Webinar Room acts as a conference room for departmental and online meetings, discussions with students, and dialogues with affiliated hospitals via the internet. The Imaging Center is equipped with a Sectra® medical educational platform, CAE Vimedix® Virtual Medical Imaging Ultrasound Training System, and Philipps Lumify® Ultrasound devices to train students to conduct and interpret sonographic images. Moreover, the Complete Anatomy® program is made available to all our students. CONCLUSION: The layout of our newly created Anatomy Facilities allows for all aspects of modern medical education mentioned in the literature. These educational modalities and teaching approaches are highly appreciated by our faculty and students. Moreover, these technologies allowed for a smooth transition from on-site anatomy teaching to online education during the COVID pandemic.

Group A Streptococcus Necrotizing Lymphadenitis: A Case Report.

Necrotizing lymphadenitis (NL) is a rare entity that can occur as a complication of bacterial cervical lymphadenitis (CL) and is characterized by unilateral or bilateral cervical lymphadenopathy. NL most commonly presents in females and most reports have been in Japan. In this case, we present a 37-year-old male with no significant past medical history who presented with an unusual presentation and clinical course of NL. Initial workup for Epstein-Barr Virus (EBV) and other infectious etiology was negative. Yet, aspiration later revealed Group A Streptococcus. When the patient's pain and swelling did not subside with the initial antibiotic and supportive treatment, the patient underwent a repeat aspiration and biopsy that revealed a necrotic mass or lymph node. NL is uncommon and rarely due to infectious etiology. However, this marks a case in which a Group A Streptococcus was shown to be associated with subsequent necrotic lymph nodes and should allow practitioners to further consider an infectious etiology in the differential diagnosis of NL.

Implementation of Learning Communities at Khalifa University College of Medicine and Health Sciences, Abu Dhabi, United Arab Emirates.

Learning community programs have been widely implemented in higher education institutions, including many accredited medical schools in North America. Learning communities have been shown to create a sense of belonging, enhance teaching and learning, and promote an inclusive educational environment that reinforces collaboration, professionalism, and wellbeing. Based on their demonstrated success, a learning community program was included in the development of Khalifa University College of Medicine and Health Sciences (KU CMHS), the first medical school in the capital city of Abu Dhabi and the first to offer a postbaccalaureate, Doctor of Medicine (MD) degree in the United Arab Emirates (UAE). Named the Falcon Learning Communities (FLCs), the program adopted the core values of the Learning Communities Institute and integrated them into curricular, co-curricular, and extra-curricular programming. This paper presents an overview on the development of the FLC program, its implication for both students and faculty, preliminary feedback from teachers and learners, and considerations for future work.

Novel MIS 3D NAV Single Step Pedicle Screw System (SSPSS): Workflow, Accuracy and Initial Clinical Experience.

STUDY DESIGN: Prospective case series. OBJECTIVE: SSPSS (single step pedicle screw system) was developed for minimally invasive spine surgery. We performed this study to report on safety, workflow, and our initial clinical experience with this novel technique. METHODS: The prospective study was conducted on patients who underwent pedicle screw fixation between October 2017 and April 2018 using a novel single step 3D navigated pedicle screw system for MIS. Outcome measurements were obtained from intraoperative computerized tomography. The images were evaluated to determine pedicle wall penetration. We used a grading system to assess the severity of the pedicle wall penetration. Breaches were classified as grade 1 (<2 mm), grade 2 (2-4 mm), or grade 3 (<4 mm),1 and as cranial, caudal, medial, and lateral. RESULTS: Our study includes 135 screws in 24 patients. SSPSS eliminated K-wires and multiple steps traditionally necessary for MIS pedicle screw insertion. The median time per screw was 2.45 minutes. 3 screws were corrected intraoperatively. Pedicle wall penetration occurred in 14 screws (10%). Grade 1 breaches occurred in 4 screws (3%) and grade 2 breaches occurred in 10 screws (7%). Lateral breaches were observed more often than medial breaches. The accuracy rate in our study was 90% (Grade 0 breach). No revision surgeries were needed and no complications occurred. CONCLUSIONS: Our study suggests that SSPSS could be a safe, accurate, and efficient tool. Our accuracy rate is comparable to that found in the literature.

3D Printable Conducting and Biocompatible PEDOT-graft-PLA Copolymers by Direct Ink Writing.

Tailor-made polymers are needed to fully exploit the possibilities of additive manufacturing, constructing complex, and functional devices in areas such as bioelectronics. In this paper, the synthesis of a conducting and biocompatible graft copolymer which can be 3D printed using direct melting extrusion methods is shown. For this purpose, graft copolymers composed by conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and a biocompatible polymer polylactide (PLA) are designed. The PEDOT-g-PLA copolymers are synthesized by chemical oxidative polymerization between 3,4-ethylenedioxythiophene and PLA macromonomers. PEDOT-g-PLA copolymers with different compositions are obtained and fully characterized. The rheological characterization indicates that copolymers containing below 20 wt% of PEDOT show the right complex viscosity values suitable for direct ink writing (DIW). The 3D printing tests using the DIW methodology allows printing different parts with different shapes with high resolution (200 µm). The conductive and biocompatible printed patterns of PEDOT-g-PLA show excellent cell growth and maturation of neonatal cardiac myocytes cocultured with fibroblasts.

Mixed Bullous-Eczematous Contact Dermatitis From a Black Henna Tattoo in an African American Female With Sickle Cell Disease With Post-Dermatitis Pain.

Traditionally practiced in East Asian and Southeast Asian countries, Henna tattooing has gained western popularity in creating temporary decorative patterns on the skin. Derived from the Lawsonia inermis shrub prevalent in Asia/Southeast Asia, the leaves of this plant are ground to create a paste with a brown pigment commonly called Mehndi or Henna which have deep-rooted cultural values/practices. The pure organic form of these compounds has few reported side effects. However, with gaining western popularity, synthetic additives to the natural paste to create color variation, shorten application times, and increase shelf-life have led to an increase in the incidence of adverse reactions. Namely attributed to synthetic compounds like para-phenylenediamine (PPD) or para-toluylenediamine, this synthetic type of mixture is called black henna. Although multiple types of adverse reactions with black henna have been documented as an eczematous type of reaction, few if any cases of adverse reactions of black henna affecting patients with sickle cell disease (SCD) have been documented. In this case, we aim to present an atypical mixed bullous-eczematous contact dermatitis reaction secondary to a PPD containing black henna dye applied to the skin of a patient with homozygous SCD. We intend to raise awareness of the deleterious cosmetic sequelae and chronic post-dermatitis pain manifestations which may arise in patients with SCD, as the popularity of black henna tattooing grows in the United States where SCD is one of the most prevalent hemoglobinopathies amongst black Americans.

Medical Ethics and the Biopsychosocial Model for Patient Care: A Case Analysis for Improved Communication, Clinical Time, and Error Avoidance.

The practice of interdisciplinary medicine is one of the most effective and cooperative forms of medical management, which optimizes clinical care and outcomes for a patient. This model of care affords the patient the benefit of receiving the best available therapeutic options from specialists who are experts in their respective disciplines, which would otherwise be limited when compared with the clinical expertise from a single provider managing multiple co-morbidities. However, poor communication between each specialized team managing a patient's care can result in redundancies and superfluous treatment that can have deleterious clinical outcomes that impede the physician-patient relationship and question the bioethical principles of clinical practice. Having a medical provider like an internist who is the primary medical provider for a patient anchors reinforces the physician-patient relationship through familiarity and continuous involvement in the gross clinical course of a patient. Specialty care provides a very focused and limiting scope of practice. However, whether practicing specialty care or being a generalist, utilizing clinical tools, such as the biopsychosocial model and routinely using bioethical principles during clinical encounters, not only help extract pertinent information from the patient's medical history but also furthers the continuity of clinical care by understanding the global context of the patient's medical history. This is a case analysis that exemplifies sub-optimal outcomes in patient care due to undermining the critical role of an internist in patient care and clinical management in addition to challenging several bioethical principles of clinical care. It also highlights the importance of how using the biopsychosocial model of care can avoid clinical errors, improve interdisciplinary and patient communication, and, ultimately, optimize the patient-physician relationship and clinical care.

Indirect Decompression Failure After Lateral Lumbar Interbody Fusion-Reported Failures and Predictive Factors: Systematic Review.

BACKGROUND: In patients with symptomatic lumbar stenosis undergoing lateral transpsoas approach for lumbar interbody fusion (LLIF) surgery, it is not always clear when indirect decompression is sufficient in order to achieve symptom resolution. Indirect decompression failure (IDF), defined as "postoperative persistent symptoms of nerve compression with or without a second direct decompression surgery to reach adequate symptom resolution," is not widely reported. This information, however, is critical to better understand the indications, the potential, and the limitations of indirect decompression. OBJECTIVE: The purpose of this study was to systematically review the current literature on IDF after LLIF. METHODS: A literature search was performed on PubMed. We included randomized controlled trials and prospective, retrospective, case-control studies, and case reports. Information on sample size, demographics, procedure, number and location of involved levels, follow-up time, and complications were extracted. RESULTS: After applying the exclusion criteria, we included 9 of the 268 screened articles that reported failure. A total of 632 patients were screened in these articles and detailed information was provided. Average follow-up time was 21 months. Overall reported incidence of IDF was 9%. CONCLUSION: Failures of decompression via LLIF are inconsistently reported and the incidence is approximately 9%. IDF failure in LLIF may be underreported or misinterpreted as a complication. We propose to include the term "IDF" as described in this article to differentiate them from complications for future studies. A better understanding of why IDF occurs will allow surgeons to better plan surgical intervention and will avoid revision surgery.

Ten-Step Minimally Invasive Cervical Decompression via Unilateral Tubular Laminotomy: Technical Note and Early Clinical Experience.

BACKGROUND: Minimally invasive techniques utilizing tubular retractors have become an increasingly popular approach to the spinal column. The concept of a unilateral laminotomy for bilateral decompression (ULBD), first applied in the lumbar spine, has recently been applied to the cervical spine for the treatment of cervical spondylotic myelopathy (CSM). A better understanding of the indications and surgical techniques is required to effectively educate surgeons on how to appropriately and safely perform tubular cervical laminotomy via ULBD. OBJECTIVE: To describe a 10-step technique for minimally invasive cervical laminotomy and report our early clinical experience. METHODS: A retrospective review identified 15 patients with CSM who were treated with this procedure. Visual analogue scale (VAS), neck disability index (NDI), and modified Japanese Orthopaedic Association (mJOA) scores were obtained pre- and postoperatively. RESULTS: The mean age of the 15 patients was 73.1 ± 6.8 yr. The median number of levels treated was 1 (range 1-3). Mean operative time was 125.3 ± 30.8 or 81.7 ± 19.2 min per level. Mean estimated blood loss was 57.3 ± 24.6 cc. Median postoperative hospital length of stay was 36 h. No complications were encountered. Median follow-up was 18 mo. Mean pre- and postoperative VAS were 6.4 ± 2.4 and 1.0 ± 0.8, respectively (P < .001). Mean pre- and postoperative NDI were 46.4 ± 19.2 and 7.0 ± 6.9, respectively (P < .001). Mean pre- and postoperative Mjoa were 11.3 ± 2.5 and 14.5 ± 0.5, respectively (P < .001). CONCLUSION: In our early clinical experience, minimally invasive cervical ULBD is safe and effective. Adherence to the presented 10-step technique will allow surgeons to safely address bilateral cervical pathology while avoiding complications.

A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.

BACKGROUND: Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of minimally invasive drug sampling techniques, such as dried blood spots (DBS), may enhance the enrollment of children in PK studies. The objectives of this study were to compare solithromycin concentrations in DBS with those in liquid plasma samples (LPS) and to quantify the effects of modeling DBS concentrations on the results of a population PK model. METHODS: Comparability analysis was performed on matched DBS and LPS solithromycin concentrations collected from two different phase 1 clinical trials of solithromycin treatment in children (clinicaltrials.gov #NCT01966055 and #NCT02268279). Comparability of solithromycin concentrations was evaluated based on DBS:LPS ratio, median percentage prediction error, and median absolute percentage prediction error. The effect of correcting DBS concentrations for both hematocrit and protein binding was investigated. In addition, a previously published population PK model (NONMEM) was leveraged to compare parameter estimates resulting from either DBS or LPS concentrations. RESULTS: A total of 672 paired DBS-LPS concentrations were available from 95 subjects (age: 0-17 years of age). The median (range) LPS and DBS solithromycin concentrations were 0.3 (0.01-12) mcg/mL and 0.32 (0.01-14) mcg/mL, respectively. Median percentage prediction error and median absolute percentage prediction error of raw DBS to LPS solithromycin concentrations were 5.26% and 22.95%, respectively. In addition, the majority of population PK parameter estimates resulting from modeling DBS concentrations were within 15% of those obtained from modeling LPS concentrations. CONCLUSIONS: Solithromycin concentrations in DBS were similar to those measured in LPS and did not require correction for hematocrit or protein binding.

Population Pharmacokinetics and Safety of Solithromycin following Intravenous and Oral Administration in Infants, Children, and Adolescents.

Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5). PK samples were collected after the first and multidose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (n = 13; median age, 16 years [age range, 12 to 17 years]) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and postmenstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg i.v. daily and oral dosing of 20 mg/kg on day 1 (800-mg adult maximum) followed by 10 mg/kg on days 2 to 5 (400-mg adult maximum) would achieve a pediatric solithromycin exposure consistent with the exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to the study treatment. (The phase 1 pediatric studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01966055 and NCT02268279.).

Atypical Presentation of Infective Endocarditis: A Case Report.

The American Heart Association defines Infective Endocarditis (IE) or bacterial endocarditis as an infection caused by bacteria that enter the bloodstream and settle in the heart lining, heart valve, or blood vessel [1]. IE is considered the fourth most common life-threatening infection syndrome after sepsis, pneumonia, and intra-abdominal abscess. In 2010, IE was associated with 1.58 million disability-adjusted life years, or years of healthy life lost, as a result of death and nonfatal illness and impairment [2,3]. The variability in clinical presentation of IE and the importance of early diagnosis require a diagnostic strategy that is prompt for disease detection and specific for its exclusion across all forms of the disease [2].

Entamoeba Histolytica: Updates in Clinical Manifestation, Pathogenesis, and Vaccine Development.

Entamoeba histolytica is the responsible parasite of amoebiasis and remains one of the top three parasitic causes of mortality worldwide. With increased travel and emigration to developed countries, infection is becoming more common in nonendemic areas. Although the majority of individuals infected with E. histolytica remain asymptomatic, some present with amoebic colitis and disseminated disease. As more is learned about its pathogenesis and the host's immune response, the potential for developing a vaccine holds promise. This narrative review outlines the current knowledge regarding E. histolytica and E. dispar and insight in the development of a vaccine.

A CTD-Pfizer collaboration: manual curation of 88,000 scientific articles text mined for drug-disease and drug-phenotype interactions.

Improving the prediction of chemical toxicity is a goal common to both environmental health research and pharmaceutical drug development. To improve safety detection assays, it is critical to have a reference set of molecules with well-defined toxicity annotations for training and validation purposes. Here, we describe a collaboration between safety researchers at Pfizer and the research team at the Comparative Toxicogenomics Database (CTD) to text mine and manually review a collection of 88,629 articles relating over 1,200 pharmaceutical drugs to their potential involvement in cardiovascular, neurological, renal and hepatic toxicity. In 1 year, CTD biocurators curated 254,173 toxicogenomic interactions (152,173 chemical-disease, 58,572 chemical-gene, 5,345 gene-disease and 38,083 phenotype interactions). All chemical-gene-disease interactions are fully integrated with public CTD, and phenotype interactions can be downloaded. We describe Pfizer's text-mining process to collate the articles, and CTD's curation strategy, performance metrics, enhanced data content and new module to curate phenotype information. As well, we show how data integration can connect phenotypes to diseases. This curation can be leveraged for information about toxic endpoints important to drug safety and help develop testable hypotheses for drug-disease events. The availability of these detailed, contextualized, high-quality annotations curated from seven decades' worth of the scientific literature should help facilitate new mechanistic screening assays for pharmaceutical compound survival. This unique partnership demonstrates the importance of resource sharing and collaboration between public and private entities and underscores the complementary needs of the environmental health science and pharmaceutical communities. Database URL: http://ctdbase.org/

Design and implementation of a low power mobile CPU based embedded system for artificial leg control.

This paper presents the design and implementation of a new neural-machine-interface (NMI) for control of artificial legs. The requirements of high accuracy, real-time processing, low power consumption, and mobility of the NMI place great challenges on the computation engine of the system. By utilizing the architectural features of a mobile embedded CPU, we are able to implement our decision-making algorithm, based on neuromuscular phase-dependant support vector machines (SVM), with exceptional accuracy and processing speed. To demonstrate the superiority of our NMI, real-time experiments were performed on an able bodied subject with a 20 ms window increment. The 20 ms testing yielded accuracies of 99.94% while executing our algorithm efficiently with less than 11% processor loads.

Promise of a low power mobile CPU based embedded system in artificial leg control.

This paper presents the design and implementation of a low power embedded system using mobile processor technology (Intel Atom™ Z530 Processor) specifically tailored for a neural-machine interface (NMI) for artificial limbs. This embedded system effectively performs our previously developed NMI algorithm based on neuromuscular-mechanical fusion and phase-dependent pattern classification. The analysis shows that NMI embedded system can meet real-time constraints with high accuracies for recognizing the user's locomotion mode. Our implementation utilizes the mobile processor efficiently to allow a power consumption of 2.2 watts and low CPU utilization (less than 4.3%) while executing the complex NMI algorithm. Our experiments have shown that the highly optimized C program implementation on the embedded system has superb advantages over existing PC implementations on MATLAB. The study results suggest that mobile-CPU-based embedded system is promising for implementing advanced control for powered lower limb prostheses.

Cognitive impairment in patients with Pseudotumor Cerebri Syndrome.

INTRODUCTION: Patients with Pseudotumor Cerebri Syndrome (PTCS) may complain of difficulty in thinking or concentrating; however there has been little formal cognitive evaluation in this population. OBJECTIVE: To evaluate the characteristics and nature of cognitive impairment in patients with PTCS. METHODS: We retrospectively reviewed records of 10 patients diagnosed with PTCS who were cognitively tested at presentation. In each cognitive test, "Borderline deficit" (BD) was defined as a score more than 1 standard deviation (SD) below and "Definite Deficit" (DD) as a score more than 2 SD below the mean for age, sex and education. In each cognitive domain, impairment was defined as a single test score more than 2 SD below the mean, or scores of more than 1 SD below the mean for age, sex and education in > 50% of tests. RESULTS: Mean age of patients was 43.4 ± 13.5 years. 8/10(80%) patients were female. 3/10(30%) had papilledema; 3/10(30%) had significant cerebral venous outflow obstruction. Impairment was most commonly seen and was most severe in the WMS logical memory I (BD-44%, DD-44%), WMS logical memory II (BD-37.5%, DD-50%), RAVLT delayed recall (BD-30%, DD-40%) and RAVLT retention(BD-40%, DD-30%) tests. Evaluation of cognitive domains revealed impairment in memory and learning (80%), executive function (10%), visuo-spatial skills (30%), and language (30%). CONCLUSION: Our results indicate that patients with PTCS can have significant cognitive impairment, particularly in learning and memory. The prevalence needs to be studied in a larger cohort. The relationship of cognitive impairment with chronically elevated intracranial pressures and its role in contributing to patient morbidity needs to be investigated further.