Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation.

Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.

Observed declines in body size have differential effects on survival and recruitment, but no effect on population growth in tropical birds.

Declines in body size can be an advantageous physiological response to warming temperatures, or a result of physiological and nutritional stress. Either way, studies often assume that these climate-induced trait changes have important implications for fitness and demography. We leveraged almost three decades of capture-mark-recapture data of 51 bird species in Panama to examine if body size has changed through time, how sensitive body size is to changes in weather, and if body size impacts population demography. We evaluated two metrics of body size, structural size (wing length), and body condition (residual body mass). Over the study, wing length changed in varying directions for 88% of species (23 decrease, 22 increase), but the effects were weak, and change was only significant for two species. Conversely, body condition declined for 88% of species (45), effects were stronger, and that change was significant for 22% of species (11). This suggests that nutritional stress is likely the cause of changes in body size, not an adaptive response to warming. Precipitation metrics impacted body condition across three of our four feeding guilds, while wing length was only impacted by weather metrics for two guilds. This suggests that body condition is more sensitive to change in weather metrics compared to wing length. Lastly, we found that the impact of changes in body size on survival and recruitment was variable across species, but these relationships were in the opposite direction, ultimately resulting in no change in population growth for all but one species. Thus, while different stages (adult survival and recruitment) of populations may be impacted by body size, populations appear to be buffered from changes. The lack of an effect on population growth rate suggests that populations may be more resilient to changes in body size, with implications for population persistence under expected climate change.

Transcriptomic signatures of progression to TB disease among close contacts in Brazil.

BACKGROUND: Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB, so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. METHODS: Close contacts (≥4 hours exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically-confirmed or clinically-diagnosed pulmonary or extra-pulmonary TB disease through 24 months of follow-up was symptom-triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative PCR. Prognostic performance for incident TB was tested using receiver operating characteristic curve (ROC) analysis at 6, 9, 12, and 24 months of follow-up. RESULTS: Between June 2015 and June 2019, 1,854 close contacts were enrolled; Twenty-five progressed to incident TB, of whom 13 had microbiologically-confirmed disease. Baseline transcriptomic signature scores were measured in 1,789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile (TPP) for a prognostic test through 6 months; three (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the TPP threshold through 12 or more months of follow-up. CONCLUSIONS: Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts, to target preventive therapy administration.

Apelin-13 reverses bupivacaine-induced cardiotoxicity: an experimental study.

INTRODUCTION: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. METHODS: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg-1.min-1, and serial doses of apelin-13 (50, 150 and 450 µg.kg-1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. RESULTS: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). CONCLUSION: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

ISG15/USP18/STAT2 is a molecular hub regulating IFN I-mediated control of Dengue and Zika virus replication.

The establishment of a virus infection is the result of the pathogen's ability to replicate in a hostile environment generated by the host's immune system. Here, we found that ISG15 restricts Dengue and Zika viruses' replication through the stabilization of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signaling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2's stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host's IFN-I mediated response and promoting virus replication.

Unstructured satellite survey detects up to 20% of archaeological sites in coastal valleys of southern Peru.

Satellite survey is widely used for archaeological site discovery, but the efficacy of the method has received little systematic investigation. In this analysis, twelve study participants of different experience levels performed an unstructured remote survey of 197 km2 in the Sama and Moquegua valleys of south central Peru where previous pedestrian surveys recorded 546 archaeological sites. Results indicate an average site discovery rate of 9.3% (0-18%, 95% range). The most experienced participants detect up to 20% (17-22%) of known archaeological sites. These detection rates can be used to derive reliable site frequency estimates on the Andean coast, which can be used in planning and budgeting for field efforts and estimating demographic patterns at large spatial scales that are difficult to achieve through pedestrian survey. More generally, this analysis offers a method for deriving correction terms specific to other parts of the world. Additionally, the results can serve as a baseline for evaluating the effectiveness of emerging artificial intelligence routines for archaeological site detection.

Intra-abdominal Content Movement in Prone Versus Lateral Decubitus Position Lateral Lumbar Interbody Fusion (LLIF).

STUDY DESIGN: A prospective, anatomical imaging study of healthy volunteer subjects in accurate surgical positions. OBJECTIVE: To establish if there is a change in the position of the abdominal contents in the lateral decubitus (LD) versus prone position. SUMMARY OF BACKGROUND DATA: Lateral transpsoas lumbar interbody fusion (LLIF) in the LD position has been validated anatomically and for procedural safety, specifically in relation to visceral risks. Recently, LLIF with the patient in the prone position has been suggested as an alternative to LLIF in the LD position. MATERIALS AND METHODS: Subjects underwent magnetic resonance imaging of the lumbosacral region in the right LD position with the hips flexed and the prone position with the legs extended. Anatomical measurements were performed on axial magnetic resonance images at the L4-5 disc space. RESULTS: Thirty-four subjects were included. The distance from the skin to the lateral disc surface was 134.9 mm in prone compared with 118.7 mm in LD ( P <0.0001). The distance between the posterior aspect of the disc and the colon was 20.3 mm in the prone compared with 41.1 mm in LD ( P <0.0001). The colon migrated more posteriorly in relation to the anterior margin of the psoas in the prone compared with LD (21.7  vs . 5.5 mm, respectively; P <0.0001). 100% of subjects had posterior migration of the colon in the prone compared with the LD position, as measured by the distance from the quadratum lumborum to the colon (44.4  vs . 20.5 mm, respectively; P <0.001). CONCLUSION: There were profound changes in the position of visceral structures between the prone and LD patient positions in relation to the LLIF approach corridor. Compared with LD LLIF, the prone position results in a longer surgical corridor with a substantially smaller working window free of the colon, as evidenced by the significant and uniform posterior migration of the colon. Surgeons should be aware of the potential for increased visceral risks when performing LLIF in the prone position. LEVEL OF EVIDENCE: Level II-prospective anatomical cohort study.

Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis.

Sarcopenia is a risk factor for adverse clinical outcomes in chronic kidney disease (CKD) patients, including mortality. Diagnosis depends on adopted consensus definition and cutoff values; thus, prevalence rates are generally heterogeneous. We conducted a systematic review and meta-analysis to investigate the global prevalence of sarcopenia and its traits across the wide spectrum of CKD. A systematic search was conducted using databases, including MEDLINE and EMBASE, for observational studies reporting the prevalence of sarcopenia. We considered sarcopenia according to the consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP), the Asian Working Group for Sarcopenia, the Foundation for the National Institutes of Health Sarcopenia Project, and the International Working Group on Sarcopenia (IWGS). Subgroup analyses by CKD stages, consensus, and gender were performed. Pooled prevalence was obtained from random-effect models. A total of 140 studies (42 041 patients) across 25 countries were included in this systematic review and meta-analyses. Global prevalence of sarcopenia was 24.5% [95% confidence interval (CI): 20.9-28.3) and did not differ among stages (P = 0.33). Prevalence varied according to the consensus definition from 11% to 30%, with no significant difference (P = 0.42). Prevalence of severe sarcopenia was 21.0% (95% CI: 11.7-32.0), with higher rates for patients on dialysis (26.2%, 95% CI: 16.6-37.1) compared to non-dialysis (3.0%, 95% CI: 0-11.1; P < 0.01). Sarcopenic obesity was observed in 10.8% (95% CI: 3.5-21.2). Regarding sarcopenia traits, low muscle strength was found in 43.4% (95%CI: 35.0-51.9), low muscle mass in 29.1% (95% CI: 23.9-34.5), and low physical performance in 38.6 (95% CI: 30.9-46.6) for overall CKD. Prevalence was only higher in patients on dialysis (50.0%, 95% CI: 41.7-57.4) compared to non-dialysis (19.6%, 95% CI: 12.8-27.3; P < 0.01) for low muscle strength. We found a high global prevalence of sarcopenia in the wide spectrum of CKD. Low muscle strength, the primary sarcopenia trait, was found in almost half of the overall population with CKD. Patients on dialysis were more prevalent to low muscle strength and severe sarcopenia. Nephrology professionals should be aware of regularly assessing sarcopenia and its traits in patients with CKD, especially those on dialysis.

Should we consider sarcopenia in pediatric patients with chronic kidney disease? A preliminary cross-sectional analysis.

BACKGROUND: Pediatric patients with chronic kidney disease (CKD) frequently present an inadequate nutritional profile and musculoskeletal impairments. We investigated sarcopenia and its related traits in children and adolescents with CKD. METHODS: A cross-sectional study that enrolled pediatric patients with CKD (≥ 4 and < 18 years old). Physical function was assessed by handgrip strength and the 60-s sit-to-stand (STS-60) tests. Body composition measurement was performed by bioelectrical impedance analysis and anthropometry through mid-upper arm circumference (MUAC). Normative reference values from healthy pediatrics were used for identifying poor physical function and low MUAC. Probable sarcopenia was considered as low handgrip strength, whereas sarcopenia was defined by adding low MUAC. RESULTS: Twenty-two pediatric patients with CKD (11 ± 4 years and 59% boys) were evaluated; eight on peritoneal dialysis (36%), six on hemodialysis (27%), and eight non-dialysis (36%). Regarding sarcopenia traits, we observed low physical function by handgrip strength and STS-60 in 59% and 100% of the patients, respectively, while low MUAC in 77%. Probable sarcopenia was found in 9% and sarcopenia in 50%, but prevalence did not differ among stages. Handgrip strength was strongly associated with MUAC (r = 0.90; p < 0.001); on the other hand, the STS-60 was not significantly associated with any of the body composition variables. CONCLUSION: Among pediatric patients with CKD, the prevalence of sarcopenia and its related traits was high. Nephrology professionals should consider the assessment of sarcopenia in this population, while more evidence is needed to determine its prognostic value. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis

Abstract Background To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. Methods Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). Results ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were - 0.416 (- 0.796, - 0.060), - 0.195 (- 0.371, - 0.028), and - 0.196 (- 0.373, - 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. Conclusion Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. Trial Registration Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188.

Apelin-13 reverses bupivacaine-induced cardiotoxicity: an experimental study

Abstract Introduction: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. Methods: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg−1.min−1, and serial doses of apelin-13 (50, 150 and 450 μg.kg−1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. Results: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). Conclusion: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

Predictors of initial management failure in traumatic hemothorax: A prospective multicenter cohort analysis.

BACKGROUND: Traumatic hemothorax is common, and management failure leads to worse outcomes. We sought to determine predictive factors and understand the role of trauma center performance in hemothorax management failure. METHODS: We prospectively examined initial hemothorax management (observation, pleural drainage, surgery) and failure requiring secondary intervention in 17 trauma centers. We defined hemothorax management failure requiring secondary intervention as thrombolytic administration, tube thoracostomy, image-guided drainage, or surgery after failure of the initial management strategy at the discretion of the treating trauma surgeon. Patient-level predictors of hemothorax management failure requiring secondary intervention were identified for 2 subgroups: initial observation and immediate pleural drainage. Trauma centers were divided into quartiles by hemothorax management failure requiring secondary intervention rate and hierarchical logistic regression quantified variation. RESULTS: Of 995 hemothoraces in 967 patients, 186 (19%) developed hemothorax management failure requiring secondary intervention. The frequency of hemothorax management failure requiring secondary intervention increased from observation to pleural drainage to surgical intervention (12%, 22%, and 35%, respectively). The number of ribs fractured (odds ratio 1.12 per fracture; 95% confidence interval 1.00-1.26) and pulmonary contusion (odds ratio 2.25, 95% confidence interval 1.03-4.91) predicted hemothorax management failure requiring secondary intervention in the observation subgroup, whereas chest injury severity (odds ratio 1.58; 95% confidence interval 1.17-2.12) and initial hemothorax volume evacuated (odds ratio 1.10 per 100 mL; 95% confidence interval 1.05-1.16) predicted hemothorax management failure requiring secondary intervention after pleural drainage. After adjusting for patient characteristics in the logistic regression model for hemothorax management failure requiring secondary intervention, patients treated at high hemothorax management failure requiring secondary intervention trauma centers were 6 times more likely to undergo an intervention after initial hemothorax management failure than patients treated in low hemothorax management failure requiring secondary intervention trauma centers (odds ratio 6.18, 95% confidence interval 3.41-11.21). CONCLUSION: Failure of initial management of traumatic hemothorax is common and highly variable across trauma centers. Assessing patient selection for a given management strategy and center-level practices represent opportunities to improve outcomes from traumatic hemothorax.

Gold Nanoparticle-Based Microfluidic Chips for Capture and Detection of Circulating Tumor Cells.

Liquid biopsy has progressed to its current use to diagnose and monitor cancer. Despite the recent advances in investigating cancer detection and diagnosis strategies, there is still a room for improvements in capturing CTCs. We developed an efficient CTC detection system by integrating gold nanoparticles with a microfluidic platform, which can achieve CTC capture within 120 min. Here, we report our development of a simple and effective way to isolate CTCs using antibodies attached on gold nanoparticles to the surface of a lateral filter array (LFA) microdevice. Our method was optimized using three pancreatic tumor cell lines, enabling the capture with high efficiency (90% ± 3.2%). The platform was further demonstrated for isolating CTCs from patients with metastatic pancreatic cancer. Our method and platform enables the production of functionalized, patterned surfaces that interact with tumor cells, enhancing the selective capture of CTCs for biological assays.

Home-Based Emergency Preparedness for Families of Children and Youth With Special Healthcare Needs: A Scoping Review.

Children and youth with special healthcare needs (CYSHCN) are at disproportionate risk of harm from widespread disasters and from life-safety emergencies. These risks may be mitigated by providing preparedness training and support to family caregivers. We conducted a scoping review to identify and map the scholarly literature on home-focused preparedness of families with CYSHCN. Our search strategy yielded 22 relevant articles; 13 pertained to life-safety emergencies, 5 centered on widespread disasters, and 4 addressed preparedness on multiple scales. Approaches to measure or attempt to improve emergency preparedness levels in CYSHCN and their families were diverse and included interviews and focus groups; didactic, video-based, or side-by-side instruction; simulated medical crises; and provisioning of emergency kits. For the studies that involved an intervention (n=15, 68%), several proxy indicators of preparedness were used, including caregiver knowledge, skill, or comfort level with managing emergencies that could affect their CYSHCN; completion of preparedness tasks; and reduction in adverse clinical outcomes. Despite the varied methodologies, prevailing themes in the studies were that family caregivers of CYSHCN felt underprepared for emergencies and disasters, desired training to improve their preparedness at home, and benefited from such trainings, at least in the short term, across domains of self-efficacy, skill, and health outcomes of their CYSHCN. Although more research is needed to compare preparedness interventions and evaluate the durability of these interventions in larger, more diverse samples of CYSHCN and their families, our findings support incorporating preparedness training into preventive care encounters and the hospital-to-home transition.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics.

Natural products (NPs) from plants, fungi, animals, and microorganisms have historically played important roles in drug discovery [...].

Sustainable volume sweep imaging lung teleultrasound in Peru: Public health perspectives from a new frontier in expanding access to imaging.

Background: Pulmonary disease is a common cause of morbidity and mortality, but the majority of the people in the world lack access to diagnostic imaging for its assessment. We conducted an implementation assessment of a potentially sustainable and cost-effective model for delivery of volume sweep imaging (VSI) lung teleultrasound in Peru. This model allows image acquisition by individuals without prior ultrasound experience after only a few hours of training. Methods: Lung teleultrasound was implemented at 5 sites in rural Peru after a few hours of installation and staff training. Patients were offered free lung VSI teleultrasound examination for concerns of respiratory illness or research purposes. After ultrasound examination, patients were surveyed regarding their experience. Health staff and members of the implementation team also participated in separate interviews detailing their views of the teleultrasound system which were systematically analyzed for key themes. Results: Patients and staff rated their experience with lung teleultrasound as overwhelmingly positive. The lung teleultrasound system was viewed as a potential way to improve access to imaging and the health of rural communities. Detailed interviews with the implementation team revealed obstacles to implementation important for consideration such as gaps in lung ultrasound understanding. Conclusions: Lung VSI teleultrasound was successfully deployed to 5 health centers in rural Peru. Implementation assessment revealed enthusiasm for the system among members of the community along with important areas of consideration for future teleultrasound deployment. This system offers a potential means to increase access to imaging for pulmonary illness and improve the health of the global community.

Sustained secretion of human growth hormone from TheraCyte devices encapsulated with PiggyBac-engineered retinal pigment epithelium cells.

Growth hormone (GH) deficiency is characterized by impaired growth and development, and is currently treated by repeated administration of recombinant human GH (hGH). Encapsulated cell therapy (ECT) may offer a less demanding treatment-strategy for long-term production and release of GH into circulation. We used PiggyBac-based (PB) transposon delivery for engineering retinal pigment epithelial cells (ARPE-19), and tested a series of viral and non-viral promoters as well as codon-optimization to enhance transgene expression. Engineered cells were loaded into TheraCyte macrocapsules and secretion was followed in vitro and in vivo. The cytomegalovirus (CMV) promoter supports strong and persistent transgene expression, and we achieved clonal cell lines secreting over 6 µg hGH/106 cells/day. Codon-optimization of the hGH gene did not improve secretion. ARPE-19 cells endured encapsulation in TheraCyte devices, and resulted in steady hormone release for at least 60 days in vitro. A short-term pilot experiment in immunodeficient SCID mice demonstrated low systemic levels of hGH from a single 40 µL capsule implanted subcutaneously. No significant increase in weight increase or systemic hGH was detected after 23 days in the GH-deficient lit/SCID mouse model using 4.5 µL capsules loaded with the highest secreting clone of ARPE-19 cells. Our results demonstrate that PB-mediated engineering of ARPE-19 is an efficient way to generate hormone secreting cell lines compatible with macroencapsulation, and our CMV-driven expression cassette allows for identification of clones with high level and long-term secretory activity without addition of insulator elements. Our results pave the way for further in vivo studies of encapsulated cell therapy.

The Utility of 18 F-NaF-Positron Emission Tomography/Computed Tomography in Measuring the Metabolic Activity of the Aging Spine : Implications for Osteoporosis.

STUDY DESIGN: Cross-sectional; observational. OBJECTIVES: To determine whether sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) can be used to monitor decreased bone turnover with aging in the spine. BACKGROUND: Osteoporosis is characterized by structural changes in the bone such as decreased bone mineral density leading to an increased risk for fractures. An imaging modality capable of identifying molecular changes that precede these structural changes could be critical for the early diagnosis and monitoring of osteoporosis and other metabolic bone disorders. MATERIALS AND METHODS: The potential of 18 F-sodium fluoride (NaF)-PET/CT in detecting changes in bone turnover associated with aging was examined in the lumbar spine of 88 healthy volunteers (43 females, 45 males; mean age 44.6 yr). Regions of interest equal to the trabecular body of the L1 to L4 vertebrae were used to calculate the mean standardized uptake value (SUVmean) and average Hounsfield unit (HU) values. Receiver-operating characteristic curve analysis with an area under the curve using the Wilson/Brown method was generated to assess the value of NaF uptake (SUVmean) in predicting osteoporosis as defined by HU-threshold values. To determine the correlation among global SUVmean, mean HU values, and age, the Spearman correlation test was performed on images acquired at 90 minutes postinjection. RESULTS: There was a significant negative correlation between NaF SUVmean and age in females ( P < 0.0001, r = -0.59), and a weaker, but also significant correlation in males ( P = 0.03, r = -0.32). In females only, there was a significant correlation between NaF uptake and age at all acquisition time points. Measured NaF uptake increased by 10% to 15% with acquisition time in both sexes, from 45 to 90 minutes and from 90 to 180 minutes. CONCLUSIONS: NaF-PET/CT detects decreased vertebral bone turnover with aging, particularly in females. Measured NaF uptake increased with PET acquisition time after tracer injection, which must be considered in follow-up studies monitoring disease development and treatment effects.

Leclercia Adecarboxylata and Pseudomonas Oryzihabitans Infection after Achilles Tendon Repair: A Case Report and Literature Review.

Leclercia adecarboxylata and Pseudomonas oryzihabitans are two bacteria rarely seen in human infections. We present an unusual case of a patient who developed a localized infection with these bacteria after repair of a ruptured Achilles tendon. We also present a review of the literature regarding infection with these bacteria within the lower extremity.