Endoscopic Removal of a Single, Painless, Juvenile Polyp in the Small Intestine Causing Anemia.

Juvenile polyps are the most common gastrointestinal polyps in childhood. Typically, they are located in the colon and present with intermittent and painless hematochezia. A few case reports have described juvenile polyps in the small intestine, all presenting as intussusception requiring surgery. We report an isolated juvenile polyp in the small intestine presenting with painless anemia, identified using video capsule endoscopy, and removed via enteroscopy.

cisExpress: motif detection in DNA sequences.

MOTIVATION: One of the major challenges for contemporary bioinformatics is the analysis and accurate annotation of genomic datasets to enable extraction of useful information about the functional role of DNA sequences. This article describes a novel genome-wide statistical approach to the detection of specific DNA sequence motifs based on similarities between the promoters of similarly expressed genes. This new tool, cisExpress, is especially designed for use with large datasets, such as those generated by publicly accessible whole genome and transcriptome projects. cisExpress uses a task farming algorithm to exploit all available computational cores within a shared memory node. We demonstrate the robust nature and validity of the proposed method. It is applicable for use with a wide range of genomic databases for any species of interest. AVAILABILITY: cisExpress is available at www.cisexpress.org.

Chaste: an open source C++ library for computational physiology and biology.

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to 're-invent the wheel' with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials.

Conference report: WHO meeting summary on mRNA-based tuberculosis vaccine development.

Tuberculosis (TB) is a global health emergency. Across the globe, approximately 2 billion people are currently infected with Mycobacterium tuberculosis (Mtb), and of those, 5-10% may progress to become ill and potentially transmit the bacterium. In 2021, nearly 10.6 million people developed TB disease and 1.6 million died. There is an urgent need for accelerated development of new TB-focused interventions, in particular, improved TB vaccines. However, progress in developing highly effective TB vaccines has been slow and is chronically under-resourced. The mRNA vaccine platform may offer an opportunity to accelerate development of new TB vaccines. In April 2023, the World Health Organization convened global experts to discuss the feasibility and potential value of mRNA-based vaccines for TB. Here we report on meeting deliberations related to the current TB vaccine pipeline and potential novel antigens, the status of efforts to identify correlates of protection, potential clinical development strategies and considerations for community acceptance of new TB vaccines based on this relatively new platform. The role of industry collaborations, ethics, social science, and responsibility to the global community regarding transparency and manufacturing capacity building were discussed through expert presentations and panel sessions. The overall conclusion of the meeting is that mRNA-based vaccines constitute a potentially powerful new tool for reducing the global burden of TB.

Gastric-Type Enteric Duplication Cyst Communicating with an Accessory Pancreatic Duct.

Enteric duplication cysts are rare congenital anomalies defined by the location along the gastrointestinal tract from which they communicate as well as the epithelial lining they contain. Enteric duplication cysts in communication with the pancreas are an even rarer subset that are often difficult to diagnose due to nonspecific presenting symptoms. In a pediatric patient with a history of recurrent pancreatitis episodes, a pancreatic duplication should be on the differential. High clinical suspicion and specific imaging characteristics can aid in the diagnosis. The management of pancreatic duplication cysts requires surgical excision or drainage procedures to alleviate symptoms and prevent associated complications such as recurrent pancreatitis, bleeding, bowel obstruction, or malignancy. Here we present a case of a gastric duplication cyst in communication with an accessory pancreatic lobe with special focus on the preoperative workup, intraoperative findings, and histopathologic examination. [Pediatr Ann. 2022;51(8):e324-e327.].

An unusual case of hydranencephaly presenting with an anterior midline cyst, a posterior calcified mass, cerebellar hypoplasia and occlusion of the posterior cerebral arteries.

We present an unusual case of severe hydranencephaly in a term infant who presented with the following additional unique features, which were discovered on CT, MRI and MR angiography examinations: (1) occlusion of the bilateral posterior cerebral arteries, (2) absence of the occipital lobes, (3) an ovoid calcified mass sitting on the inner table of the occipital bone, (4) severe cerebellar hypoplasia, (5) a dysmorphic cystic diencephalon, (6) a large anterior midline cyst just above the cribriform plate and (7) absence of the falx. These imaging findings were confirmed at autopsy.

Epstein-Barr virus-associated intracranial leiomyosarcoma in an HIV-positive adolescent.

SUMMARY: A 17-year-old African American female with human immunodeficiency virus infection presented with an unresectable intracranial neoplasm with mass effect upon the brainstem. Stereotactic biopsy revealed an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Radiation therapy and gemcitabine were used to shrink the mass with the aim to make it surgically resectable. Prolonged neutropenia and recurrent skin infections led to the discontinuation of gemcitabine. The mass stabilized after radiation therapy and has decreased in size in 15 months of follow-up. EBV has been demonstrated in most smooth muscle tumors associated with acquired immunodeficiency syndrome and other immunocompromised states. This is the first documented case of an EBV-positive intracranial leiomyosarcoma in a pediatric human immunodeficiency virus patient.

Multi-scale computational modelling in biology and physiology.

Recent advances in biotechnology and the availability of ever more powerful computers have led to the formulation of increasingly complex models at all levels of biology. One of the main aims of systems biology is to couple these together to produce integrated models across multiple spatial scales and physical processes. In this review, we formulate a definition of multi-scale in terms of levels of biological organisation and describe the types of model that are found at each level. Key issues that arise in trying to formulate and solve multi-scale and multi-physics models are considered and examples of how these issues have been addressed are given for two of the more mature fields in computational biology: the molecular dynamics of ion channels and cardiac modelling. As even more complex models are developed over the coming few years, it will be necessary to develop new methods to model them (in particular in coupling across the interface between stochastic and deterministic processes) and new techniques will be required to compute their solutions efficiently on massively parallel computers. We outline how we envisage these developments occurring.

Model format for a vaccine stability report and software solutions.

A session of the International Association for Biologicals Workshop on Stability Evaluation of Vaccine, a Life Cycle Approach was devoted to a model format for a vaccine stability report, and software solutions. Presentations highlighted the utility of a model format that will conform to regulatory requirements and the ICH common technical document. However, there need be flexibility to accommodate individual company practices. Adoption of a model format is premised upon agreement regarding content between industry and regulators, and ease of use. Software requirements will include ease of use and protections against inadvertent misspecification of stability design or misinterpretation of program output.

WHO/KFDA workshop on stability evaluation of vaccines, Seoul, Korea, 23-25 April 2008.

In April 2008, the World Health Organization and the Korea Food & Drug Administration jointly organized a workshop on evaluating vaccine stability. The main objective of the workshop was to facilitate implementing newly established WHO guidelines. The value of stability studies in understanding vaccine characteristics, establishing shelf-life and release specifications, and monitoring the stability post-market was well explained. Optimal designs for goal-based stability studies were proposed and appropriate statistical analyses presented. A statistical model (the term "estimation model" was adopted) based on regression analysis of potency loss over storage time elapsed, was elaborated for describing the stability profile of vaccines. This model was believed to provide a more precise description of the stability characteristics of a vaccine than the current "compliance model". The use of both models was discussed in relation to specific examples and case studies. A document format for assisting standardized stability report was discussed as a possible annex to the WHO stability guidelines adopted in 2006. The participants agreed that a future revision of vaccine stability guidance should highlight the estimation model and that WHO should provide additional training to support national regulatory authorities with statistical design and analysis, and to assist their transition from the compliance model towards wider use of the estimation model.

A Case of Primary Paratesticular Wilms Tumor in an Undescended Testis.

Extrarenal Wilms tumor is rare. We describe the first reported case of primary paratesticular extrarenal Wilms tumor with regional metastasis in 8-month old male with left undescended testis. Patient underwent left radical orchiectomy with regional lymph node excision. The inguinal node and paratesticular mass demonstrated the classic Wilms triphasic pattern, stained positively for WT-1 and demonstrated no loss of heterozygosity of chromosomes 1p and 16q. Work-up was negative for primary renal Wilms tumor or distant metastasis. Patient underwent adjuvant chemoradiation therapy for stage III disease. Patient is currently 2 years of age with no evidence of recurrence or metastatic disease.

Report on eighth WHO meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses: Chicago, USA, 23-24 August 2016.

In August 2016, the World Health Organization (WHO) convened the "Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses" to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines, and to identify areas where WHO can promote the development of such vaccines. Participants included approximately 120 representatives of academia, the vaccine industry, research and development funders, and regulatory and public health agencies. They reviewed the draft WHO preferred product characteristics (PPCs) of vaccines that could address prioritized unmet public health needs and discussed the challenges facing the development of such vaccines, especially for low- and middle-income countries (LMIC). They defined the data desired by public-health decision makers globally and explored how to support the progression of promising candidates into late-stage clinical trials and for all countries. This report highlights the major discussions of the meeting.

A Lady 'in Proper Proportions'? Feminism, Lytton Strachey, and Florence Nightingale's Reputation, 1918-39.

Lytton Strachey's Eminent Victorians has long been regarded as a watershed in attitudes to Victorian culture, widely seen as having instigated a revolutionary backlash against the values and heroes of the Victorian era in England. Its impact, however, on the reputations of his four subjects-Thomas Arnold, General Gordon, Cardinal Manning and Florence Nightingale-has been subjected to surprisingly little scholarly attention. Drawing on the work of gender historians, this article reassesses Strachey's effect on the reputation of Nightingale, using biographies and contemporary reviews of Eminent Victorians. It argues that, far from 'debunking' the famous nurse as is generally assumed, Strachey in many ways enhanced her reputation and rendered her a plausible icon for English feminists of the 1920s and 1930s.

Off-label use of vaccines.

This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as approved by the regulatory authorities (or "label"1), and the recommendations for use issued by public health advisory bodies at national and international levels. Differences between public health recommendations and the product label regarding the vaccine use can lead to confusion at the level of vaccinators and vaccinees and possibly result in lower compliance with national vaccination schedules. In particular, in many countries, the label may contain regulatory restrictions and warnings against vaccination of specific population groups (e.g. pregnant women) due to a lack of evidence of safety from controlled trials at the time of initial licensure of the vaccine, while public health authorities may recommend the same vaccine for that group, based on additional post-marketing data and benefit risk analyses. We provide an overview of the different responsibilities between regulatory authorities and public health advisory bodies, and the rationale for off-label use2 of vaccines, the challenges involved based on the impact of off-label use in real-life. We propose to reduce off-label use of vaccines by requiring the manufacturer to regularly adapt the label as much as possible to the public health needs as supported by new evidence. This would require manufacturers to collect and report post-marketing data, communicate them to all stakeholders and regulators to extrapolate existing evidence (when acceptable) to other groups or to other brands of a vaccine (class effect3). Regulatory authorities have a key role to play by requesting additional post-marketing data, e.g. in specific target groups. When public health recommendations for vaccine use that are outside labelled indications are considered necessary, good communication between regulatory bodies, public health authorities, companies and health care providers or vaccinators is crucial. Recommendations as well as labels and label changes should be evidence-based. The rationale for the discrepancy and the recommended off-label use of a vaccine should be communicated to providers.

Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. METHODS AND RESULTS: LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. CONCLUSIONS: LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.

Simulating Cardiac Electrophysiology Using Unstructured All-Hexahedra Spectral Elements.

We discuss the application of the spectral element method to the monodomain and bidomain equations describing propagation of cardiac action potential. Models of cardiac electrophysiology consist of a system of partial differential equations coupled with a system of ordinary differential equations representing cell membrane dynamics. The solution of these equations requires solving multiple length scales due to the ratio of advection to diffusion that varies among the different equations. High order approximation of spectral elements provides greater flexibility in resolving multiple length scales. Furthermore, spectral elements are extremely efficient to model propagation phenomena on complex shapes using fewer degrees of freedom than its finite element equivalent (for the same level of accuracy). We illustrate a fully unstructured all-hexahedra approach implementation of the method and we apply it to the solution of full 3D monodomain and bidomain test cases. We discuss some key elements of the proposed approach on some selected benchmarks and on an anatomically based whole heart human computational model.

T-cell/histiocyte-rich large B-cell lymphoma in pediatric patients: an under-recognized entity?

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) under-recognized in the pediatric population. A meticulous workup is necessary to avoid a misdiagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or classical Hodgkin lymphoma (HL). A strong degree of suspicion and an emphasis on immunohistochemical staining are required to reach the diagnosis. Few children with advanced stage disease have been described to date. We report two pediatric patients with high stage THRLBCL and highlight their clinical and pathological features.

BAG3 myofibrillar myopathy presenting with cardiomyopathy.

Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy.

Pathology of central nervous system posttransplant lymphoproliferative disorders: lessons from pediatric autopsies.

Posttransplant lymphoproliferative disorders (PTLD) involving the central nervous system (CNS) in children are uncommon and can prove diagnostically challenging. The clinical and imaging characteristics of CNS PTLD can overlap with those of infection, hemorrhage, and primary CNS tumors. Some cases of CNS PTLD remain clinically unsuspected and are diagnosed postmortem. We report 6 instances of CNS PTLD in children, 2 of which were limited to the CNS and were unsuspected before autopsy. In our autopsy series, PTLD was found outside the CNS in 4 out of 6 cases. Since CNS PTLD has a poor prognosis and the presentation can be subtle, unsuspected, and high grade, it is important to maintain a high index of suspicion and to perform imaging and brain biopsy whenever clinically appropriate. In the presence of leptomeningeal involvement, the diagnosis could be made by cerebral spinal fluid examination.