B Cell Lymphomas of the GI Tract.

PURPOSE OF THE REVIEW: Primary GI lymphomas of B cell origin are a diverse group of lymphomas. In this article, we provide an overview of the diagnosis, pathologic and molecular features, and management of these varied lymphomas. RECENT FINDINGS: The most common primary GI lymphomas are diffuse large B cell lymphoma (DLBCL) and marginal zone lymphomas (MZL), but follicular lymphomas (FL), mantle cell lymphomas (MCL), post-transplant lymphoproliferative disorders (PTLD), and Burkitt lymphoma of the GI tract also occur. Many features of these lymphomas are similar to their nodal counterparts, but certain clinical and biological aspects are unique. Diagnostic and treatment strategies for these lymphomas continue to evolve over time. There are ongoing discoveries about the unique pathophysiology, molecular characteristics, and complications of primary B cell GI lymphomas that are already leading to improvements in management of this histologically diverse set of lymphomas.

Evaluating the Use of Alternative Seating with Kindergarteners at Risk for Emotional and Behavioral Disorders.

Characteristics of emotional and behavioral disorders (EBD) include learning difficulties that cannot be explained by intellectual, sensory, or health factors and difficulties in building or maintaining interpersonal relationships with peers and teachers. Children with or at risk for an EBD often have a tendency to have negative experiences in school and engage in challenging behavior in the classroom including out-of-seat behavior. One possible antecedent manipulation, alternative seating, may reduce challenging behavior and involves exchanging the typical seating in classrooms for different types of seating options. The purpose of this study was to evaluate the use of stability stools and scoop rocker chairs on in-seat behavior and on-task behavior in classrooms with kindergarten students who engaged in challenging behavior and were at risk for EBD. All three participants demonstrated improvements in in-seat behavior using both types of alternative seating compared to a standard classroom chair. On-task behavior improved for all students but was variable for two students. Teachers indicated a preference for the stability stool, whereas results were mixed between the stool and the rockers for student preference.

Contribution of Bordetella filamentous hemagglutinin and adenylate cyclase toxin to suppression and evasion of interleukin-17-mediated inflammation.

Bordetella pertussis and Bordetella bronchiseptica establish respiratory infections with notorious efficiency. Our previous studies showed that the fhaB genes of B. pertussis and B. bronchiseptica, which encode filamentous hemagglutinin (FHA), are functionally interchangeable and provided evidence that FHA-deficient B. bronchiseptica induces more inflammation in the lungs of mice than wild-type B. bronchiseptica. We show here that the robust inflammatory response to FHA-deficient B. bronchiseptica is characterized by the early and sustained influx of interleukin-17 (IL-17)-positive neutrophils and macrophages and, at 72 h postinoculation, IL-17-positive CD4(+) T cells, suggesting that FHA allows the bacteria to suppress the development of an IL-17-mediated inflammatory response. We also show that the cyaA genes of B. pertussis and B. bronchiseptica, which encode adenylate cyclase toxin (ACT), are functionally interchangeable and that ACT, specifically its catalytic activity, is required for B. bronchiseptica to resist phagocytic clearance but is neither required for nor inhibitory of the induction of inflammation if bacteria are present in numbers sufficient to persist during the first 3 days postinoculation. Incubation of bone marrow-derived macrophages with a ΔcyaA strain caused decreased production of IL-1ß and increased production of tumor necrosis factor alpha (TNF-α) and IL-12, while incubation with a ΔcyaA ΔfhaB strain caused increased production of IL-23. These data suggest that FHA and ACT both contribute to suppress the recruitment of neutrophils and the development of an IL-17-mediated immune response. To our knowledge, this is the first demonstration of a microbial pathogen suppressing IL-17-mediated inflammation in vivo as a strategy to evade innate immunity.

Data we can trust.

"On behalf of all authors of the submission, I warrant that the work is original and scientifically accurate ..." If you've submitted a manuscript to the Journal of Clinical Investigation or JCI Insight, this phrase should sound familiar. This statement is the very first thing that we ask authors to verify for every new submission. While this may seem like a simple formality or just another screen to click through, certifying the accuracy of information presented to the journal is essential to the publishing process and scientific integrity. Data accuracy forms the foundation of the scientific enterprise, and without it, the enterprise risks crumbling.

TAFRO Syndrome and Elusive Diagnosis of Idiopathic Multicentric Castleman Disease Treated with Empiric Anti-Interleukin-6 Therapy.

TAFRO syndrome is defined by the presence of thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal dysfunction (R), and organomegaly (O) and can be seen with idiopathic multicentric Castleman disease (iMCD) or as an isolated process without iMCD. Although the diagnosis of iMCD in patients with TAFRO can be challenging to make, iMCD should remain high on the differential diagnosis. Similar to iMCD, the pathophysiology of TAFRO is not well understood but is thought to be related to hypercytokinemia, with interleukin (IL)-6 playing a pivotal role. Anti-IL-6 monoclonal antibody therapy is an effective treatment modality for iMCD, but to date, there is no clear guidance on treatment of TAFRO in the absence of definitive diagnosis of iMCD, leading to suboptimal management and high morbidity. We report a case of TAFRO syndrome and demonstrate benefit with the empiric use of anti-IL-6 antibody therapy in the context of delayed diagnosis of iMCD.

Figure errors, sloppy science, and fraud: keeping eyes on your data.

Recent reports suggest that there has been an increase in the number of retractions and corrections of published articles due to post-publication detection of problematic data. Moreover, fraudulent data and sloppy science have long-term effects on the scientific literature and subsequent projects based on false and unreproducible claims. At the JCI, we have introduced several data screening checks for manuscripts prior to acceptance in an attempt to reduce the number of post-publication corrections and retractions, with the ultimate goal of increasing confidence in the papers we publish.

Serendipitous discovery of an immunoglobulin-binding autotransporter in Bordetella species.

We describe the serendipitous discovery of BatB, a classical-type Bordetella autotransporter (AT) protein with an approximately 180-kDa passenger domain that remains noncovalently associated with the outer membrane. Like genes encoding all characterized protein virulence factors in Bordetella species, batB transcription is positively regulated by the master virulence regulatory system BvgAS. BatB is predicted to share similarity with immunoglobulin A (IgA) proteases, and we showed that BatB binds Ig in vitro. In vivo, a Bordetella bronchiseptica DeltabatB mutant was unable to overcome innate immune defenses and was cleared from the lower respiratory tracts of mice more rapidly than wild-type B. bronchiseptica. This defect was abrogated in SCID mice, suggesting that BatB functions to resist clearance during the first week postinoculation in a manner dependent on B- and T-cell-mediated activities. Taken together with the previous demonstration that polymorphonuclear neutrophils (PMN) are critical for the control of B. bronchiseptica in mice, our data support the hypothesis that BatB prevents nonspecific antibodies from facilitating PMN-mediated clearance during the first few days postinoculation. Neither of the strictly human-adapted Bordetella subspecies produces a fully functional BatB protein; nucleotide differences within the putative promoter region prevent batB transcription in Bordetella pertussis, and although expressed, the batB gene of human-derived Bordetella parapertussis (B. parapertussis(hu)) contains a large in-frame deletion relative to batB of B. bronchiseptica. Taken together, our data suggest that BatB played an important role in the evolution of virulence and host specificity among the mammalian-adapted bordetellae.

Comparison of phylogenetically distinct Histoplasma strains reveals evolutionarily divergent virulence strategies.

Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an H. capsulatum isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized Histoplasma isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successful in vitro infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis. Importance: Histoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinical H. capsulatum isolate that was collected from an HIV(+) individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is dependent on the presence of cell wall α-(1,3)-glucan. Surprisingly, comparison of WU24 with two previously characterized isolates revealed that many conclusions regarding relative strain virulence and certain hallmarks of histoplasmosis are dependent on the inoculum size.

Speech-language pathologists' assessment and intervention practices with multilingual children.

Within predominantly English-speaking countries such as the US, UK, Canada, New Zealand, and Australia, there are a significant number of people who speak languages other than English. This study aimed to examine Australian speech-language pathologists' (SLPs) perspectives and experiences of multilingualism, including their assessment and intervention practices, and service delivery methods when working with children who speak languages other than English. A questionnaire was completed by 128 SLPs who attended an SLP seminar about cultural and linguistic diversity. Approximately one half of the SLPs (48.4%) reported that they had at least minimal competence in a language(s) other than English; but only 12 (9.4%) reported that they were proficient in another language. The SLPs spoke a total of 28 languages other than English, the most common being French, Italian, German, Spanish, Mandarin, and Auslan (Australian sign language). Participants reported that they had, in the past 12 months, worked with a mean of 59.2 (range 1-100) children from multilingual backgrounds. These children were reported to speak between two and five languages each; the most common being: Vietnamese, Arabic, Cantonese, Mandarin, Australian Indigenous languages, Tagalog, Greek, and other Chinese languages. There was limited overlap between the languages spoken by the SLPs and the children on the SLPs' caseloads. Many of the SLPs assessed children's speech (50.5%) and/or language (34.2%) without assistance from others (including interpreters). English was the primary language used during assessments and intervention. The majority of SLPs always used informal speech (76.7%) and language (78.2%) assessments and, if standardized tests were used, typically they were in English. The SLPs sought additional information about the children's languages and cultural backgrounds, but indicated that they had limited resources to discriminate between speech and language difference vs disorder.

Phonemic awareness and early spelling skills in urban Australian Aboriginal and non-Aboriginal children.

This study investigated the phonological awareness and early spelling skills of 10 Australian Aboriginal and 10 non-Aboriginal children in their first year of schooling at urban schools. Phonological awareness was assessed using a standardized test (the Queensland University Inventory of Literacy), and children completed a standard spelling task that required them to generate spelling attempts in response to 12 line drawings of familiar animals. Spelling was analysed using the Spelling Scoring Sensitivity procedure. All children performed within the normal range for scores on the QUIL. However, as a group, Aboriginal children performed more poorly than their non-Aboriginal peers. Statistically significant differences were found on the subtests non-word spelling, non-word reading, and phoneme segmentation. Both formal scoring and informal observations were used to examine the spelling skills of participants. Possible explanations of the differences between groups are discussed in terms of health and cultural factors, and implications for the education of Aboriginal children are suggested.

The impact of otitis media on cognitive and educational outcomes.

Otitis media is a common disease in childhood that can adversely affect cognitive and educational outcomes. The literature in this area is equivocal, and findings may be influenced by research design. The impact of otitis media on individual children's development appears to depend on the inter-relationship between several factors. Children who have early-onset otitis media (under 12 months) are at high risk of developing long-term speech and language problems. Otitis media has been found to interact negatively with pre-existing cognitive or language problems. For biological or environmental reasons, some populations have a pattern of early onset, higher prevalence and episodes of longer duration; this pattern leads to a higher risk of long-term speech and language problems. These factors suggest that Indigenous children may be at higher risk of cognitive and educational sequelae than non-Indigenous children.

Middle ear disease in Aboriginal children in Perth: analysis of hearing screening data, 1998-2004.

OBJECTIVE: To describe diagnoses and correlates of middle ear disease in Aboriginal primary school children in a targeted school-testing program in Perth, Western Australia. DESIGN AND SETTING: Analysis of records of ear testing carried out over a 6-year period in three primary schools in Perth. PARTICIPANTS: Aboriginal children of primary school age (4-12 years) who attended the schools on the day of testing. Data on middle ear disease and hearing impairment were available for 119 and 94 children, respectively, from their first test. MAIN OUTCOME MEASURES: Proportions of children with middle ear disease and hearing loss. RESULTS: Middle ear disease was diagnosed in 50 children (42.0%; 95% CI, 33.0%-51.4%). Rates were lower in older children (P = 0.002) but did not differ according to season of testing. Hearing loss (mild or moderate) was detected in 18 children (19.1%; 95% CI, 11.8%-28.6%). Hearing impairment was also less prevalent in older children (P = 0.007) and had no association with season of testing. CONCLUSIONS: Middle ear disease is a significant problem for Aboriginal children in Perth, and is associated with mild-moderate hearing loss. Health authorities must continue to focus on appropriate identification and management of the disease in this population.

Autoregulation is essential for precise temporal and steady-state regulation by the Bordetella BvgAS phosphorelay.

The Bordetella BvgAS virulence control system is prototypical of phosphorelays that use a polydomain sensor and a response regulator to control gene expression in response to environmental cues. BvgAS controls the expression of at least three distinct phenotypic phases (Bvg(-), Bvg(i), and Bvg(+)) by differentially regulating the expression of at least four classes of genes. Among the loci regulated by BvgAS is bvgAS itself. We investigated the role of autoregulation in the ability of BvgAS to control multiple gene expression patterns in a temporal and steady-state manner by constructing Bordetella bronchiseptica strains in which the bvgAS promoter was replaced with constitutively active promoters. Our results show that positive autoregulation of bvgAS transcription is required for the temporal expression of multiple phenotypic phases that occurs in response to a shift from Bvg(-)-phase conditions to Bvg(+)-phase conditions. Autoregulation was also shown to contribute to steady-state regulation; it influences the sensitivity of the system in response to subtle differences in signal intensity. In addition, considered in relation to BvgA and BvgS activities demonstrated in vitro, our results provide insight into how BvgA and BvgS function mechanistically.