Post-surgical readmission risk factors in otolaryngology/head and neck surgery.

BACKGROUND: Otolaryngology patients are a high-readmission-risk group due to the complexity of surgeries, significant alterations to speech and swallowing functions, and high postoperative complications risk. METHODS: A retrospective review was performed on patients who underwent otolaryngologic surgery at a single-academic-institution between March 2019 and February 2020. RESULTS: Among 365 discharges, 21 patients had unplanned readmissions within 30 days. On univariable analysis, acute myocardial infarction, number of total comorbidities, prior chemotherapy/radiation, active smoking, airway surgery, and enteral feeding, and on multivariable analysis, prior chemotherapy/radiation and active smoking were identified as significant readmission risk factors. Readmission risk increased from 2.43% to 7.48% and 41.67% with the addition of each risk factor. CONCLUSION: Nearly 75% of the readmissions were due to potentially preventable reasons. By identifying and proactively intervening on "at risk" patients during the perioperative timeframe, complications and readmission can be reduced, thereby improving the overall quality of care delivered.

Lifestyle Interventions to Prevent Type 2 Diabetes in Women with a History of Gestational Diabetes: A Systematic Review and Meta-Analysis through the Lens of Health Equity.

BACKGROUND: Type 2 diabetes mellites is one of the health problems disproportionally affecting people with low socioeconomic statuses. Gestational diabetes mellites increases the risk of type 2 diabetes by up to ten-fold for women. Lifestyle interventions prevent type 2 diabetes in women with prior gestational diabetes. However, it is unknown if similar effectiveness can be expected for all population subgroups. OBJECTIVE: This study aims to assess the prevention of type 2 diabetes in women with prior gestational diabetes using population characteristics according to the PROGRESS (place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, and social capital) criteria. METHODS: MEDLINE, CINAHL, EMBASE, PubMed, PsycINFO, Web of Science, and EBM Reviews databases were searched for interventional studies of diet, physical activity, or behavioural interventions published up to 21 February 2023. Random effects subgroup meta-analysis was conducted to evaluate the association of population characteristics and intervention effects. RESULTS: All studies were conducted in high-income countries or middle-income countries. Two-thirds of the studies reported on race/ethnicity and education level. Less than one-third reported on place (urban/rural), occupation, and socioeconomic status. None reported on religion or social capital. Studies from high-income countries (MD = -1.46; 95% CI: -2.27, -0.66, I2 = 70.46, p < 0.001) showed a greater reduction in bodyweight compared with the studies conducted in middle-income countries (MD = -0.11; 95% CI: -1.12, 0.89, I2 = 69.31, p < 0.001) (p for subgroup difference = 0.04). CONCLUSION: There are significant equity gaps in the evidence for the prevention of type 2 diabetes in women with prior gestational diabetes due to reports on population characteristics being poor. Interventions may be less effective in reducing bodyweight in women from middle-income countries compared to high-income countries. Collecting and analysing data related to equity is needed to understand the effect of lifestyle interventions on type 2 diabetes for different population subgroups.

Electrocardiographic Interference on Bispectral Index Monitor: A Case of Crossed Wires.

The Bispectral Index (BIS) has been widely utilized to monitor patients' levels of consciousness during anesthesia. Despite its practicality and prevalence, BIS monitors have been reported to show erroneous readings due to various factors that interfere with the proper reading of the brain's electrical activity. We present a case where the BIS monitor misinterpreted the patient's cardiac activity as her neural activity and resulted in a falsely elevated BIS number despite proper placement and lack of underlying patient medical condition, including neurological injury. It is crucial to remain vigilant about monitoring and understanding BIS readings to assess patients' awareness and effectiveness of anesthesia properly.

Orthodontic loading activates cell-specific autophagy in a force-dependent manner.

INTRODUCTION: Orthodontic tooth movement (OTM) relies on bone remodeling and controlled aseptic inflammation. Autophagy, a conserved homeostatic pathway, has been shown to play a role in bone turnover. We hypothesize that autophagy participates in regulating bone remodeling during OTM in a force-dependent and cell type-specific manner. METHODS: A split-mouth design was used to load molars with 1 of 3 force levels (15, 30, or 45 g of force) in mice carrying a green fluorescent protein-LC3 transgene to detect cellular autophagy. Fluorescent microscopy and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation and its correlation with force level. Cell type-specific antibodies were used to identify cells with green fluorescent protein-positive puncta (autophagosomes) in periodontal tissues. RESULTS: Autophagic activity increased shortly after loading with moderate force and was associated with the expression of bone turnover, inflammatory, and autophagy markers. Different load levels resulted in altered degrees of autophagic activation, gene expression, and osteoclast recruitment. Autophagy was specifically induced by loading in macrophages and osteoclasts found in the periodontal ligament and alveolar bone. Data suggest autophagy participates in regulating bone turnover during OTM. CONCLUSIONS: Autophagy is induced in macrophage lineage cells by orthodontic loading in a force-dependent manner and plays a role during OTM, possibly through modulation of osteoclast bone resorption. Exploring the roles of autophagy in OTM is medically relevant, given that autophagy is associated with oral and systemic inflammatory conditions.

Promoting Cross-Sector Collaborations to Address Intimate Partner Violence in Health Care Delivery Systems Using a Quality Assessment Tool.

Background: As part of a Domestic Violence and Health care Partnership (DVHCP) project in California, 19 leadership teams consisting of representatives from domestic violence agencies and health care delivery systems in California came together to improve care related to intimate partner violence (IPV). We evaluated the impact of a Quality Assessment/Quality Improvement (QA/QI) tool on health care delivery systems' ability to collaborate with victim service agencies to address IPV. Methods: Each leadership team completed the QA/QI tool every 6 months between 2014 and 2017. Fifteen clinics that completed the tool at least twice are included in this analysis. Results: The largest changes noted in the QA/QI tool were having written protocols for assessing for IPV, providers distributing educational safety cards about IPV to patients, scripts for providers on how to assess and support survivors of IPV, trainings led by IPV agency advocates, and support for staff to discuss difficult cases. Conclusions: Implementation of a QA/QI tool can guide health care delivery systems to make changes in provider practices and clinic protocols to improve care and support for survivors of IPV. Such clinic-level changes may support providers to more readily or consistently integrate addressing IPV in clinical encounters while facilitating and promoting cross-sector collaborations with victim service advocacy and related social service agencies.

Roles of autophagy in orthodontic tooth movement.

INTRODUCTION: Orthodontic tooth movement (OTM) relies on efficient remodeling of alveolar bone. While a well-controlled inflammatory response is essential during OTM, the mechanism regulating inflammation is unknown. Autophagy, a conserved catabolic pathway, has been shown to protect cells from excess inflammation in disease states. We hypothesize that autophagy plays a role in regulating inflammation during OTM. METHODS: A split-mouth design was used to force load molars in adult male mice, carrying a GFP-LC3 transgene for in vivo detection of autophagy. Confocal microscopy, Western blot, and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation in tissues of loaded and control molars at time points after force application. Rapamycin, a Food and Drug Administration-approved immunosuppressant, was injected to evaluate induction of autophagy. RESULTS: Autophagy activity increases shortly after loading, primarily on the compression side of the tooth, and is closely associated with inflammatory cytokine expression and osteoclast recruitment. Daily administration of rapamycin, an autophagy activator, led to reduced tooth movement and osteoclast recruitment, suggesting that autophagy downregulates the inflammatory response and bone turnover during OTM. CONCLUSIONS: This is the first demonstration that shows that autophagy is induced by orthodontic loading and plays a role during OTM, likely via negative regulation of inflammatory response and bone turnover. Exploring roles of autophagy in OTM holds great promise, as aberrant autophagy is associated with periodontal disease and its related systemic inflammatory disorders.

Coating Medpor® Implant with Tissue-Engineered Elastic Cartilage.

Inert biomaterials used for auricular reconstruction, which is one of the most challenging and diverse tasks in craniofacial or head and neck surgery, often cause problems such as capsule formation, infection, and skin extrusion. To solve these problems, scaffold consisting of inert biomaterial, high-density polyethylene (Medpor®) encapsulated with neocartilage, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) was created using a tissue engineering strategy. PLGA scaffold without Medpor® was created to serve as the control. Scaffolds were vacuum-seeded with rabbit chondrocytes, freshly isolated from the ear by enzymatic digestion. Then, cell-seeded scaffolds were implanted subcutaneously in the dorsal pockets of nude mice. After 12 weeks, explants were analyzed by histological, biochemical, and mechanical evaluations. Although the PLGA group resulted in neocartilage formation, the PLGA-Medpor® group demonstrated improved outcome with the formation of well-surrounded cartilage around the implants with higher mechanical strength than the PLGA group, indicating that Medpor® has an influence on the structural strength of engineered cartilage. The presence of collagen and elastin fibers was evident in the histological section in both groups. These results demonstrated a novel method of coating implant material with engineered cartilage to overcome the limitations of using biodegradable scaffold in cartilage tissue regeneration. By utilizing the patient's own chondrocytes, our proposed method may broaden the choice of implant materials while minimizing side effects and immune reaction for the future medical application.

Decellularized pulp matrix as scaffold for mesenchymal stem cell mediated bone regeneration.

Scaffolds that are used for bone repair should provide an adequate environment for biomineralization by mesenchymal stem cells (MSCs). Recently, decellularized pulp matrices (DPM) have been utilized in endodontics for their high regenerative potential. Inspired by the dystrophic calcification on the pulp matrix known as pulp stone, we developed acellular pulp bioscaffolds and examined their potential in facilitating MSCs mineralization for bone defect repair. Pulp was decellularized, then retention of its structural integrity was confirmed by histological, mechanical, and biochemical evaluations. MSCs were seeded and proliferation, osteogenic gene expression, and biomineralization were assessed to verify DPM's osteogenic effects in vitro. MicroCT, energy-dispersive X-ray (EDX), and histological analyses were used to confirm that DPM seeded with MSCs result in greater mineralization on rat critical-sized defects than that without MSCs. Overall, our study proves DPM's potential to serve as a scaffolding material for MSC-mediated bone regeneration for future craniofacial bone tissue engineering.

Machine learning in orthodontics: Introducing a 3D auto-segmentation and auto-landmark finder of CBCT images to assess maxillary constriction in unilateral impacted canine patients.

OBJECTIVES: To (1) introduce a novel machine learning method and (2) assess maxillary structure variation in unilateral canine impaction for advancing clinically viable information. MATERIALS AND METHODS: A machine learning algorithm utilizing Learning-based multi-source IntegratioN frameworK for Segmentation (LINKS) was used with cone-beam computed tomography (CBCT) images to quantify volumetric skeletal maxilla discrepancies of 30 study group (SG) patients with unilaterally impacted maxillary canines and 30 healthy control group (CG) subjects. Fully automatic segmentation was implemented for maxilla isolation, and maxillary volumetric and linear measurements were performed. Analysis of variance was used for statistical evaluation. RESULTS: Maxillary structure was successfully auto-segmented, with an average dice ratio of 0.80 for three-dimensional image segmentations and a minimal mean difference of two voxels on the midsagittal plane for digitized landmarks between the manually identified and the machine learning-based (LINKS) methods. No significant difference in bone volume was found between impaction ([2.37 ± 0.34] [Formula: see text] 104 mm3) and nonimpaction ([2.36 ± 0.35] [Formula: see text] 104 mm3) sides of SG. The SG maxillae had significantly smaller volumes, widths, heights, and depths (P < .05) than CG. CONCLUSIONS: The data suggest that palatal expansion could be beneficial for those with unilateral canine impaction, as underdevelopment of the maxilla often accompanies that condition in the early teen years. Fast and efficient CBCT image segmentation will allow large clinical data sets to be analyzed effectively.

The Inhibition of Radial and Axial Micromovement of Bone Scaffold with Gelfoam® and Titanium Mesh Fixation and Its Effects on Osteointegration.

A major drawback of nanocomposite scaffolds in bone tissue engineering is dimensional shrinkage after the fabrication process. Shrinkage yields gaps between the scaffold and host bone in the defect site and eventually causes failure in osteointegration by micromovement. The present study was conducted using titanium (Ti) mesh and Gelfoam® to prevent radial and axial micromovement, respectively. A critical-sized defect (CSD) was created in the center of the calvarium of Sprague Dawley rats to implant porous polydopamine-laced hydroxyapatite collagen calcium silicate (HCCS-PDA), a novel nanocomposite scaffold. Gelfoam® was applied around the edge of the defect, and then the HCCS-PDA scaffold was inserted in the defect area. Ti mesh was placed between the periosteum and skin right, above the inserted scaffold site. There were two test groups, with a fixture (Gelfoam® and Ti mesh) and without a fixture, each group contained five animals. The rats were sacrificed after three months post-operation. The explanted calvaria underwent micro-CT scanning and a push-out test to quantify osteointegration and mechanical strength between the scaffold and host bone. Histological analysis of undecalcified bone was performed by grinding resin infiltrated calvaria blocks to prepare 10 µm slices. Osteointegration was higher in the group with fixation than without fixation. Movement of the HCCS-PDA scaffold in the gap resulted in diminished osteointegration. With fixation, the movement was inhibited and osteointegration became prominent. Here we present a successful method of preventing axial and radial movement of scaffolds using Gelfoam® and Ti mesh. Applying this fixture, we expect that an HCCS-PDA scaffold can repair CSD more effectively.

Effect of pore size in bone regeneration using polydopamine-laced hydroxyapatite collagen calcium silicate scaffolds fabricated by 3D mould printing technology.

OBJECTIVE: The pore size of the scaffold is a critical factor in repairing large bone defect. Here, we investigated the potential of bone regeneration using novel nanocomposite polydopamine-laced hydroxyapatite collagen calcium silicate (HCCS-PDA) scaffolds with two different pore sizes, 250 and 500 µm. SAMPLES/SETTING: A total of 12 male Sprague-Dawley rats were implanted with HCCS-PDA scaffold with pore size of either 250 or 500 µm into surgically created critical-sized defect (CSD). METHODS: HCCS-PDA scaffolds were fabricated using mould printing technique. The effect of pore size on mechanical strength of the scaffolds was assessed by compression testing. After seeding with rat mesenchymal stem cells (rMSCs), the scaffolds were implanted, and new bone formation was evaluated using microCT and histomorphometric analysis after 8 weeks. RESULTS: MicroCT and histology analysis demonstrated restricted peripheral new bone formation in either dural or periosteal side and limited new bone formation in the 250 µm pore scaffold. Conversely, the 500-µm pore scaffold showed more penetration of new bone into the scaffold and greater bone regeneration in the rat CSD. CONCLUSION: Based on our results, which demonstrated improved new bone formation in 500 µm pores scaffold, we can conclude that effective scaffold pore size that induces osteointegration and bone regeneration is around 500 µm for HCCS-PDA nanocomposite scaffold.

Osteogenic potential of mesenchymal stem cells from rat mandible to regenerate critical sized calvarial defect.

Although bone marrow-derived mesenchymal stem cells (MSCs) have been extensively explored in bone tissue engineering, only few studies using mesenchymal stem cells from mandible (M-MSCs) have been reported. However, mesenchymal stem cells from mandible have the potential to be as effective as femur-derived mesenchymal stem cells (F-MSCs) in regenerating bone, especially in the orofacial regions, which share embryonic origin, proximity, and accessibility. M-MSCs were isolated and characterized using mesenchymal stem cell-specific markers, colony forming assay, and multi-potential differentiation. In vitro osteogenic potential, including proliferation, osteogenic gene expression, alkaline phosphatase activity, and mineralization, was examined and compared. Furthermore, in vivo bone formations of F-MSCs and M-MSCs in rat critical sized defect were evaluated using microCT and histology. M-MSCs from rat could be successfully isolated and expanded while preserving their MSC's characteristics. M-MSCs demonstrated a comparable proliferation and mineralization potentials and in vivo bone formation as F-MSCs. M-MSCs is a promising cell source candidate for craniofacial bone tissue engineering.

CDDO-Me, Sulforaphane and tBHQ attenuate the RANKL-induced osteoclast differentiation via activating the NRF2-mediated antioxidant response.

Metabolic bone diseases are global public health concerns and are primarily caused by uncontrolled osteoclast (OC) formation and activation. During OC differentiation, intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can serve as the signaling molecules to promote osteoclastic genes expression. Nuclear factor erythroid-2 related factor 2 (NRF2), a master mediator of cellular antioxidant response, also plays a critical role in OC differentiation through the regulation of redox homeostasis. In this study, we investigated the effects of three NRF2 inducers on osteoclastogenesis, including Bardoxolone methyl (CDDO-Me), Sulforaphane (SFN), and tert-butylhydroquinone (tBHQ). By treating RAW cells with three compounds, we found that NRF2 was activated and its downstream antioxidant genes were upregulated, and the RANKL-induced intracellular ROS production and osteoclastogenesis were impaired. Additionally, the expression of nuclear factor of activated T cells c1 (NFATC1), C-FOS and tumor necrosis factor alpha (TNFα) were inhibited after acute exposures (6 h) to the three compounds. Furthermore, suppressed the expression of osteoclast differentiation-associated genes, tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), matrix metalloproteinase-9 (MMP-9) and dendritic cell-specific transmembrane protein (DC-STAMP) were observed after prolonged exposures (5 days) to the compounds. Taken together, these results suggest that CDDO-Me, SFN and tBHQ attenuate RANKL-induced osteoclastogenesis via activation of NRF2-mediated antioxidant response. Among these compounds, relatively low concentrations of CDDO-Me showed stronger active and inhibitory effects on antioxidant response and osteoclastogenesis, respectively.

Diagnosis and staging of caries using spectral factors derived from the blue laser-induced autofluorescence spectrum.

OBJECTIVE: The aim of this study was to identify the factors derived from the 405nm laser-induced autofluorescence (AF) spectra that could be used to diagnose and stage caries. MATERIALS AND METHODS: Teeth (20 teeth per stage) were classified as sound, stage II, III, and IV based on a visual and tactile inspection. The specimens were re-examined and reclassified based on micro-CT analysis. From the teeth, the AF was obtained using a 405nm laser. Three spectral factors (spectral slope at 550-600nm, area under the curve at 500-590nm, and two-peak ratio between 625 and 667nm) were derived from the AF spectra. Using these factors, the diagnosis and staging of caries were tested, and the results were compared with those of DIAGNOdent. RESULTS: After micro-CT analysis, only 13, 11, and 13 teeth were reclassified as stages II, III, and IV, respectively. The reclassified groups showed less data overlap between the stages, and the spectral slope was 40.1-74.6, 27.5-39.6, 11.1-27.4, and 1.0-9.7 for sound, stage II, III, and IV, respectively. The differentiation of stages III and IV using DIAGNOdent appeared to be difficult due to the considerable data overlap. CONCLUSION: Among the factors tested, the spectral slope at 550-600nm showed the best match with the caries specimens, in which their stage had been identified precisely. CLINICAL SIGNIFICANCE: The 405nm laser-induced AF spectra can be applied to the diagnosis and staging of caries alone or in conjunction with conventional methods, such as visual, tactile, and X-ray inspection.

Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.

Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. Previously, we determined that decreased expression of the cytosolic pentose phosphate pathway (PPP) enzyme transaldolase activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan. Here we report that transaldolase (tald-1) deficiency impairs mitochondrial function in vivo, as evidenced by altered mitochondrial morphology, decreased respiration, and increased cellular H2O2 levels. Lifespan extension from knockdown of tald-1 is associated with an oxidative stress response involving p38 and c-Jun N-terminal kinase (JNK) MAPKs and a starvation-like response regulated by the transcription factor EB (TFEB) homolog HLH-30. The latter response promotes autophagy and increases expression of the flavin-containing monooxygenase 2 (fmo-2). We conclude that cytosolic redox established through the PPP is a key regulator of mitochondrial function and defines a new mechanism for mitochondrial regulation of longevity.

Comparison of blood pool and extracellular gadolinium chelate for functional MR evaluation of vascular thoracic outlet syndrome.

OBJECTIVE: To compare performance of single-injection blood pool agent (gadofosveset trisodium, BPA) against dual-injection extracellular contrast (gadopentetate dimeglumine, ECA) for MRA/MRV in assessment of suspected vascular TOS. MATERIALS AND METHODS: Thirty-one patients referred for vascular TOS evaluation were assessed with BPA (n=18) or ECA (n=13) MRA/MRV in arm abduction and adduction. Images were retrospectively assessed for: image quality (1=non-diagnostic, 5=excellent), vessel contrast (1=same signal as muscle, 4=much brighter than muscle) and vascular pathology by two independent readers, with a separate experienced reader providing reference assessment of vascular pathology. RESULTS: Median image quality was diagnostic or better (score ≥ 3) for ECA and BPA at all time points, with BPA image quality superior at abduction late (BPA 4.5, ECA 4, p=0.042) and ECA image quality superior at adduction-early (BPA 4.5; ECA 4.0, p=0.018). High qualitative vessel contrast (mean score ≥ 3) was observed at all time points with both BPA and ECA, with superior BPA vessel contrast at abduction-late (BPA 3.97 ± 0.12; ECA 3.73 ± 0.26, p=0.007) and ECA at adduction-early (BPA 3.42 ± 0.52; ECA 3.96 ± 0.14, p<0.001). Readers readily identified arterial and venous pathology with BPA, similar to ECA examinations. CONCLUSION: Single-injection BPA MRA/MRV for TOS evaluation demonstrated diagnostic image quality and high vessel contrast, similar to dual-injection ECA imaging, enabling identification of fixed and functional arterial and venous pathology.

Time-dependent diffusion in skeletal muscle with the random permeable barrier model (RPBM): application to normal controls and chronic exertional compartment syndrome patients.

The purpose of this work was to carry out diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Using an institutional review board approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3 T scanner at rest and after treadmill exertion at four different T(d) values. Radial diffusion values λ(rad) were computed for each of seven different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D(0), fiber diameter a, and permeability κ. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D(0) showed significant (p < 0.05) increases with exercise for volunteers, and a increased significantly (p < 0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p = 0.07), and larger permeability increases (p = 0.07) than controls. Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy.

Employee benefits in a total rewards framework.

Benefits represent one of the largest investments a company makes in its talent. However, our tendency can be to design, deliver and communicate benefits programs independently, without fully considering how those programs fit within a bigger picture of total rewards. Sure, we need to manage and execute individual benefit programs--but not at the expense of getting a real return on our more significant investment in talent. This article provides employers with perspectives on the value of managing benefits within the broader framework of total rewards, why it works and, most importantly, how to make it work.

Stimulated echo diffusion tensor imaging and SPAIR T2 -weighted imaging in chronic exertional compartment syndrome of the lower leg muscles.

PURPOSE: To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T2 -weighted (T2w) imaging. MATERIALS AND METHODS: Using an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2w imaging and stimulated echo DTI were applied to eight healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in seven calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post/pre-exercise ratios) of DTI parameters. RESULTS: All diffusivities significantly increased (P < 0.0001) and FA decreased (P = 0.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (P < 0.0001). Nineteen of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8 ± 3.4% (volunteer), 7.4 ± 4.2% (normal), and 9.1 ± 7.0% (CECS) with exercise. CONCLUSION: DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment.

New targets for antivirals: the ribosomal A-site and the factors that interact with it.

Many viruses use programmed -1 ribosomal frameshifting to ensure the correct ratio of viral structural to enzymatic proteins. Alteration of frameshift efficiencies changes these ratios, in turn inhibiting viral particle assembly and virus propagation. Previous studies determined that anisomycin, a peptidyl transferase inhibitor, specifically inhibited -1 frameshifting and the ability of yeast cells to propagate the L-A and M(1) dsRNA viruses (J. D. Dinman, M. J. Ruiz-Echevarria, K. Czaplinski, and S. W. Peltz, 1997, Proc. Natl. Acad. Sci. USA 94, 6606-6611). Here we show that preussin, a pyrollidine that is structurally similar to anisomycin (R. E. Schwartz, J. Liesch, O. Hensens, L. Zitano, S. Honeycutt, G. Garrity, R. A. Fromtling, J. Onishi, and R. Monaghan, 1988. J. Antibiot. (Tokyo) 41, 1774--1779), also inhibits -1 programmed ribosomal frameshifting and virus propagation by acting at the same site or through the same mechanism as anisomycin. Since anisomycin is known to assert its effect at the ribosomal A-site, we undertook a pharmacogenetic analysis of mutants of trans-acting eukaryotic elongation factors (eEFs) that function at this region of the ribosome. Among mutants of eEF1A, a correlation is observed between resistance/susceptibility profiles to preussin and anisomycin, and these in turn correlate with programmed -1 ribosomal frameshifting efficiencies and killer virus phenotypes. Among mutants of eEF2, the extent of resistance to preussin correlates with resistance to sordarin, an eEF2 inhibitor. These results suggest that structural features associated with the ribosomal A-site and with the trans-acting factors that interact with it may present a new set of molecular targets for the rational design of antiviral compounds.