Novel Autopsy Findings in Premature Infant With Beckwith-Wiedemann Syndrome Uniparental Disomy: Multifocal Developmental Dysplastic Chrondromatous Lesions and Cortical Neuronal Heterotopias.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder that exhibits etiologic genomic imprinting characterized by molecular heterogeneity and phenotypic variability. Associations with localized developmental dysplastic chondromatous lesions and cortical neuronal heterotopias have not previously been described. CASE PRESENTATION: A 33-week gestational age female had an omphalocele and intractable hypoglycemia at birth. The placenta demonstrated placental mesenchymal dysplasia. Detection of hypermethylation of IC1 and hypomethylation of IC2 confirmed Beckwith-Wiedemann syndrome, most likely due to uniparental disomy. Additional findings included right mid-tibial and right 5-8th developmental dysplastic chondromatous lesions, absent corpus callosum and numerous right-sided cortical neuronal heterotopias, right hemihypertrophy, multiple cystic hepatic mesenchymal hamartomas and hepatic infantile hemangiomas, nisidioblastosis and cystic pancreatic lesions. The infant died with multi-organ failure and anasarca at 7 weeks of life. CONCLUSION: Beckwith-Wiedemann syndrome anomalies may include multifocal developmental dysplastic chondromatous lesions and cerebral neuronal heterotopias, lateralized, and corpus callosum aplasia.

Cell Free Microbial DNA Utilization at a Children's Hospital.

Background: We investigated the utilization of cell free microbial DNA (cfDNA) at a Children's Hospital. Materials and Methods: cfDNA results were assessed regarding the contribution to therapeutic decisions. Results: Of 80 tests on 59 children, 1 test was unevaluable. At least one agent was identified in 45/79 (57%) tests from 34/59 (58.2%) children, 34/79 (43.0%) were negative in 31/59(52.5%) children. Of 45 positive results, 24/79 (30%) were contributory, 15/79 (19%) were diagnostic, 6/79 (7.6%) were diagnostic but diagnosis could have been made with other testing modalities, and 3/79 (3.8%) were diagnostic with minimal previous workup. 21/79 (26.6%) positives were noncontributory. Of 35 negative results, 9/79 (11.4%) were contributory, 26/79 (33.0%) were noncontributory. Efficiency was 30.4-41.8%. cfDNA detected agents not detected by conventional techniques in 22/79 (27.8%), detected different agents in 9/79 (11.4%), and failed to detect agents identified by conventional techniques in 4 (5%). Conclusions: Efficiency of cfDNA was 30.4-41.8.

Establishment and characterization of a new mantle cell lymphoma cell line with a NOTCH2 mutation, Arbo.

Cell lines represent an essential tool used in preclinical research. Most hematologic malignancies have a wide array of cell lines representing their respective molecular and pathologic spectra. In mantle cell lymphoma (MCL), cell lines become specifically valuable in view of the heterogeneity of this disease. Unfortunately, the number of MCL cell lines that are available for the research community remains small, with only nine cell lines available for purchase through the American Type Culture Collection (ATCC). We have established a novel blastoid MCL cell line, isolated from the malignant pleural effusion of a 69-year-old male with refractory MCL. Arbo was fully characterized with cytogenetics, immunophenotyping, whole exome sequencing and drug sensitivity assays. One of the most notable mutations identified in Arbo (but not in normal tissue) was the missense mutation NOTCH2 R2400*, which has been proposed as a clinically significant mutation in MCL seen in 5% of cases. NOTCH2 R2400* results in a truncated Notch2 protein, leading to a more stable and active protein. Using pharmacologic inhibition of Notch2, we showed a dependence of Arbo on NOTCH2 signaling, as well as a link between CD23 expression on Arbo and NOTCH2 activity. Arbo represents a NOTCH2 mutated model that is useful in MCL as well as other lymphomas with such mutation. We plan to deposit Arbo at the ATCC to be available for the research community.

Enhancing Quality Supervision for the Delivery of Mental Health Care Through Nonspecialist Clinicians in Resource-Limited Settings.

ABSTRACT: Supervision of nonspecialist clinicians by trained mental health professionals is integral to developing capacity for providing mental health care in low-resource settings. Current supervision efforts in low-resource settings, however, are often variable in quality. Scant published literature addresses how supervision practices affect treatment outcomes; only a few studies have been published on evidence-based supervision methods. Additionally, in low-resource settings many systems-level obstacles exist in providing adequate mental health supervision to nonspecialist clinicians. This article seeks to address psychiatrists' role in providing supervision and promoting quality of care in low-resource settings. We review the literature on evidence-based supervision practices, address obstacles and current practices of providing high-quality mental health supervision in low-resource settings, and weave this knowledge with our experiences learning from the clinicians at Partners in Health in Haiti. We also discuss feasible strategies and provide recommendations for strengthening the supervision process in resource-limited settings.

Fluorescent microspheres as a positive indicator in an intratracheal infection model.

Animal models testing the ability of vaccines and therapeutic agents to prevent pathology from induced respiratory infection are an important means of testing and validating the vaccines and therapeutic agents. However, the lack of induced pathology in test subjects could be either indicative of protection or a problem with the animal model system. This work describes the improvement of a chicken model system of intratracheal infection using fluorescent microspheres as a positive indicator of infection. It was shown that fluorescent microspheres and Mycoplasma gallisepticum bacteria both dispersed to the same areas of the chicken respiratory system and that the microspheres remained detectable in the chicken lung tissue for at least 7 days following infection. The microspheres used are detectable using a black light, allowing for visualization during necropsy. Using the updated model system, three live M. gallisepticum vaccines were tested both for their ability to elicit a humoral immune response following vaccination, and for their ability to protect from air sac lesion pathology at two different time points following vaccination. Results showed the protective effects of the different M. gallisepticum vaccines prevented the induction of pathology, consistent with previous results. The presence of the fluorescent microspheres provided a positive method of identifying the properly infected chickens and a means of differentiating failed experimental infections so that those samples could be removed, resulting in improved consistency in infection results.

Mapping Movement: Applying Motion Measurement Technologies to the Psychiatric Care of Older Adults.

PURPOSE OF REVIEW: Recent advances in technology have changed the landscape of treatment for adults with mental illness. This review highlights technological innovations that may improve care for older adults with mental illness and neurocognitive disorders through the measurement and assessment of physical motion. These technologies include wearable sensors (such as smart watches and Fitbits), passive motion sensors, and smart home models that incorporate both active and passive motion technologies. RECENT FINDINGS: Clinicians have evaluated motion measurement technologies in older adults with depression, dementia, anxiety, and schizophrenia. Results from studies in dementia populations suggest that motion measurement technologies can assist clinicians in diagnosing dementia earlier through the evaluation of gait, balance, and postural kinematics. Motion detection technologies can also be used to identify mood episodes at an earlier stage by detecting subtle behavioral changes. Clinicians may use the objective data provided by technologies such as accelerometers to identify illnesses earlier, which may inform treatment decisions. The data may be used as a suitable surrogate marker for detecting depression in older adults, predicting the likelihood of falls, or quantifying physical activity in older adults with chronic mental illnesses or anxiety. Motion-based technologies also have the potential to detect physical activity for older adults residing in nursing homes. Wearable technologies are generally well tolerated in older adults, although the use of new technology and electronic health data could involve privacy and security concerns among this vulnerable population.

The impact of vaccination route on Mycoplasma gallisepticum vaccine efficacy.

Mycoplasma gallisepticum infection can lead to major financial losses for poultry producers. Control of M. gallisepticum infection in the layer industry is generally obtained through vaccination due to the nature of the multi-aged flocks in the facilities. Live vaccines can provide significant protection from the pathogenic effects of M. gallisepticum infection. However, differing management practices, including vaccination procedures, can lead to significant variations in the efficacy of the same vaccine. The site of vaccine deposition has been shown to be one important factor significantly influencing the vaccination outcome. Previous research has shown that vaccine applied to the eyes or sprayed on the head is significantly more effective than when sprayed on the body. Vaccine application to the eyes, through the nares (nasal), and 2 routes through the oral cavity were studied to further characterize the most efficient route for delivery. Results of this work demonstrate that eye drop vaccination is significantly more effective than nasal vaccination, and vaccine delivered through the oral cavity has a negligible contribution to overall vaccination outcome.

Towards a Responsive, Sustainable and Collaborative Model of Care at Toronto's Michael Garron Hospital.

In 2008, Michael Garron Hospital, transformed its approach to care delivery. The rationale: to improve quality, increase safety and boost patient and staff engagement and satisfaction. The Coordinated Care Team (CCT) model has enabled nurses to not only work to their full scopes of practice within a team of interprofessional providers and unlicensed staff, but also helped create a culture of safety and patient-centredness in a value-driven context. Critics suggest a need for more evaluation and evidence of efficacy. This article provides a rationale, discussion and evaluation of the CCT model based on data curated from implementation to 2016.

Mental Illness Among Women Referred for Psychiatric Services in a New Zealand Women's Prison.

This naturalistic exploratory study describes the characteristics of women prisoners referred to the forensic psychiatry service of the largest women's prison in New Zealand. Forensic psychiatrists diagnosed more than one-third of the referred female inmates with psychotic disorders, and they diagnosed post-traumatic stress disorder in one-fifth. The majority of the women reported substance use prior to incarceration, as well as a history of personal victimization by family violence. Of the women prisoners referred to community mental health services at release, two-thirds attended the arranged outpatient mental health follow-up appointment. This study highlights the need for secondary prevention and rehabilitation for female inmates, and it provides suggestions for intervention. Copyright © 2016 John Wiley & Sons, Ltd.

Proteomics inference of genes involved in host adaptation of Mycoplasma gallinarum.

Different from most other host-specific mycoplasmas, Mycoplasma gallinarum has been isolated from various hosts, such as poultry, pig, cattle, and sheep. The wide distribution among different hosts, the low pathogenesis, and the weak host immunological responses suggest this mycoplasma has a unique host adaptation mechanism. In this study, we applied two-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (2D LC-MS/MS) to characterize the protein profiling of M. gallinarum. Our results suggest that M. gallinarum possesses homologs of cytadhesin proteins found in other mycoplasmas lacking an organized tip organelle. Our results showed that there are possibly multiple aminopeptidase gene homologs present in M. gallinarum, which might be involved in nutrient acquisition of M. gallinarum. The information present here would be useful for future studies to identify genes responsible for the colonization and host adaptation properties of M. gallinarum.

Induction of a mycoplasma gallisepticum pMGA gene in the chicken tracheal ring organ culture model.

Genetic and molecular methods to investigate the pathogenesis of the poultry respiratory pathogen Mycoplasma gallisepticum are quite limited. Therefore, the objective of this study was to design and evaluate a functional genomics approach to identify M. gallisepticum genes involved in colonization of the poultry respiratory tract. To serve as a transcriptional reporter, a promoterless lacZ gene from Escherichia coli was cloned into the Tn4001 transposon. The transposon was used to randomly mutagenize the chromosome of the M. gallisepticum S6 strain, and a bank of 1386 transposon mutants containing lacZ fusions to mycoplasma chromosomal DNA was assembled. Each mycoplasma clone containing the lacZ reporter was independently screened in the chicken tracheal ring organ culture (TROC) model system for increased production of beta-galactosidase. A twofold or greater increase in beta-galactosidase was consistently observed for eight mutants. In one of the mutants, the transposon was inserted in a pMGA gene encoding a cell surface adhesin involved in hemagglutination. Therefore, these data indicate that screening of a M. gallisepticum transposon reporter bank with a chicken TROC model is useful for the identification of genes induced during poultry colonization and virulence.