Febrile Rhinovirus Illness During Pregnancy Is Associated With Low Birth Weight in Nepal.

BACKGROUND: Adverse birth outcomes, including low birth weight (LBW), defined as \u3c2500 \u3egrams, small-for-gestational-age (SGA), and prematurity, contribute to 60%-80% of infant mortality worldwide and may be related to infections during pregnancy. The aim of this study was to assess whether febrile human rhinovirus (HRV) illness is associated with adverse birth outcomes. METHODS: Active household-based weekly surveillance was performed for respiratory illness episodes in pregnant women as part of a community-based, prospective, randomized trial of maternal influenza immunization in rural Nepal. Rhinovirus (HRV) febrile illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia with HRV detected on mid-nasal swab. Multivariate regression analysis evaluated the association between febrile HRV respiratory illness and adverse birth outcomes. RESULTS: Overall, 96 (3%) of 3693 pregnant women had HRV-positive febrile respiratory illnesses. Infants born to pregnant women with HRV febrile illness had a 1.6-fold increased risk of being LBW compared with those with non-HRV febrile illness (28 of 96 [38%] vs 109 of 458 [24%]; relative risk [RR], 1.6; 95% confidence interval [CI], 1.1-2.3). No difference in risk of LBW was observed between infants born to mothers with non-HRV febrile respiratory illness and those without respiratory illness during pregnancy (109 of 458 [24%] vs 552 of 2220 [25%], respectively; RR, 1.0; 95% CI, 0.8-1.2). CONCLUSIONS: Febrile illness due to rhinovirus during pregnancy was associated with increased risk of LBW in a rural South Asian population. Interventions to reduce the burden of febrile respiratory illness due to rhinovirus during pregnancy may have a significant impact on LBW and subsequent infant mortality

Chromosome 7 and 19 Trisomy in Cultured Human Neural Progenitor Cells

BACKGROUND:Stem cell expansion and differentiation is the foundation of emerging cell therapy technologies. The potential applications of human neural progenitor cells (hNPCs) are wide ranging, but a normal cytogenetic profile is important to avoid the risk of tumor formation in clinical trials. FDA approved clinical trials are being planned and conducted for hNPC transplantation into the brain or spinal cord for various neurodegenerative disorders. Although human embryonic stem cells (hESCs) are known to show recurrent chromosomal abnormalities involving 12 and 17, no studies have revealed chromosomal abnormalities in cultured hNPCs. Therefore, we investigated frequently occurring chromosomal abnormalities in 21 independent fetal-derived hNPC lines and the possible mechanisms triggering such aberrations. METHODS AND FINDINGS:While most hNPC lines were karyotypically normal, G-band karyotyping and fluorescent in situ hybridization (FISH) analyses revealed the emergence of trisomy 7 (hNPC(+7)) and trisomy 19 (hNPC(+19)), in 24% and 5% of the lines, respectively. Once detected, subsequent passaging revealed emerging dominance of trisomy hNPCs. DNA microarray and immunoblotting analyses demonstrate epidermal growth factor receptor (EGFR) overexpression in hNPC(+7) and hNPC(+19) cells. We observed greater levels of telomerase (hTERT), increased proliferation (Ki67), survival (TUNEL), and neurogenesis (beta(III)-tubulin) in hNPC(+7) and hNPC(+19), using respective immunocytochemical markers. However, the trisomy lines underwent replicative senescence after 50-60 population doublings and never showed neoplastic changes. Although hNPC(+7) and hNPC(+19) survived better after xenotransplantation into the rat striatum, they did not form malignant tumors. Finally, EGF deprivation triggered a selection of trisomy 7 cells in a diploid hNPC line. CONCLUSIONS:We report that hNPCs are susceptible to accumulation of chromosome 7 and 19 trisomy in long-term cell culture. These results suggest that micro-environmental cues are powerful factors in the selection of specific hNPC aneuploidies, with trisomy of chromosome 7 being the most common. Given that a number of stem cell based clinical trials are being conducted or planned in USA and a recent report in PLoS Medicine showing the dangers of grafting an inordinate number of cells, these data substantiate the need for careful cytogenetic evaluation of hNPCs (fetal or hESC-derived) before their use in clinical or basic science applications

Elite Suppressors Harbor Low Levels of Integrated HIV DNA and High Levels of 2-LTR Circular HIV DNA Compared to HIV+ Patients On and Off HAART

Elite suppressors (ES) are a rare population of HIV-infected individuals that are capable of naturally controlling the infection without the use of highly active anti-retroviral therapy (HAART). Patients on HAART often achieve viral control to similar (undetectable) levels. Accurate and sensitive methods to measure viral burden are needed to elucidate important differences between these two patient populations in order to better understand their mechanisms of control. Viral burden quantification in ES patients has been limited to measurements of total DNA in PBMC, and estimates of Infectious Units per Million cells (IUPM). There appears to be no significant difference in the level of total HIV DNA between cells from ES patients and patients on HAART. However, recovering infectious virus from ES patient samples is much more difficult, suggesting their reservoir size should be much smaller than that in patients on HAART. Here we find that there is a significant difference in the level of integrated HIV DNA in ES patients compared to patients on HAART, providing an explanation for the previous results. When comparing the level of total to integrated HIV DNA in these samples we find ES patients have large excesses of unintegrated HIV DNA. To determine the composition of unintegrated HIV DNA in these samples, we measured circular 2-LTR HIV DNA forms and found ES patients frequently have high levels of 2-LTR circles in PBMC. We further show that these high levels of 2-LTR circles are not the result of inefficient integration in ES cells, since HIV integrates with similar efficiency in ES and normal donor cells. Our findings suggest that measuring integration provides a better surrogate of viral burden than total HIV DNA in ES patients. Moreover, they add significantly to our understanding of the mechanisms that allow viral control and reservoir maintenance in this unique patient population

Intravoxel Incoherent Motion Magnetic Resonance Imaging in Skeletal Muscle: Review and Future Directions

Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle-specific evaluations. Most studies used segmented nonlinear least squares fitting with a b-value threshold of 200 sec/mm2 to obtain IVIM parameters of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10-3  mm2 /sec, D* was 29.7 ± 38.1 × 10-3  mm2 /sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2

Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging

PurposeEvaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected.MethodsThe DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth.ResultsAcross all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models.ConclusionThese findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown

Medical imaging of tissue engineering and regenerative medicine constructs

Advancement of tissue engineering and regenerative medicine (TERM) strategies to replicate tissue structure and function has led to the need for noninvasive assessment of key outcome measures of a construct's state, biocompatibility, and function. Histology based approaches are traditionally used in pre-clinical animal experiments, but are not always feasible or practical if a TERM construct is going to be tested for human use. In order to transition these therapies from benchtop to bedside, rigorously validated imaging techniques must be utilized that are sensitive to key outcome measures that fulfill the FDA standards for TERM construct evaluation. This review discusses key outcome measures for TERM constructs and various clinical- and research-based imaging techniques that can be used to assess them. Potential applications and limitations of these techniques are discussed, as well as resources for the processing, analysis, and interpretation of biomedical images