Mixed elicitation with salicylic acid and hydrogen peroxide modulates the phenolic and iridoid pathways in Castilleja tenuiflora plants.

MAIN CONCLUSION: SA and H2O2, in single and mixed elicitation stimulate specialized metabolism and activate oxidative stress in C. tenuiflora plants. Single elicitation with salicylic acid (SA at 75 µM) and, hydrogen peroxide (at 150 µM), and mixed elicitation (75 µM SA + 150 µM H2O2) were evaluated on specialized metabolism in Castilleja tenuiflora Benth. plants. Total phenolic content (TPC), phenylalanine ammonia-lyase (PAL) activity, antioxidant enzymes and specialized metabolite profiles, as well as the expression levels of eight genes involved in phenolic (Cte-TyrDC, Cte-GOT2, Cte-ADD, Cte-AO3, Cte-PAL1, Cte-CHS1) and terpene pathways (Cte-DXS1 and Cte-G10H) and their correlation with major metabolite (verbascoside and aucubin) concentrations were investigated. TPC content (three-fold) and PAL activity (11.5-fold) increased with mixed elicitation, as well as catalase and peroxidase activity (11.3-fold and 10.8-fold, respectively), compared to single elicitation. Phenylethanoid accumulation was greatest under mixed elicitation, followed by SA and H2O2. Lignan accumulation was differential, depending on the plant part and the elicitor. Flavonoids only appeared after mixed elicitation. The high concentration of verbascoside under mixed elicitation was related to a high gene expression. Single elicitation induced iridoid accumulation in specific parts (H2O2 in aerial parts and SA in roots), whereas under mixed elicitation, it accumulated in both parts. A high concentration of aucubin in the aerial part was related to a high expression level of genes of the terpene pathway Cte-DXS1 and Cte-G10H, and in the root with Cte-G10H, while Cte-DXS1 was downregulated in this tissue in all treatments. Mixed elicitation with SA and H2O2 represents an interesting tool to increase the production of specialized metabolites in plants.

Histopathological survey of parasites harboured by the clam Tawera elliptica (Lamarck, 1818) from Chiloé Archipelago, southeastern Pacific.

Tawera elliptica (commonly known as "Almeja Juliana", is a venerid clam that inhabits sandy bottoms and is distributed from Valparaíso on the Pacific coast up to the Mar del Plata area along the Atlantic coast. Harvests of this clam have declined substantially over the last decade. Therefore, an analysis of common parasites and pathological conditions of this clam was undertaken along with histopathology. Monthly samples were prepared for routine histology for examination under light and electron microscopy. T. elliptica has a sex ratio of 1:1 and the relationship between the shell length and the wet tissue weight is not significantly different between females and males. The maximum values for de condition index and meat yield were found during the austral winter. The following parasites (and their overall prevalence) were detected: intracellular microcolonies of bacteria in digestive gland (22.9%), intestinal epithelium (9.3%) and gills (3.17%), an unidentified cyst in gills (59,3%), a Steinhausia-like intraoocytic microsporidian (5.2%), Gregarine spores (41.3%), ciliated protozoa (16.7%), two metazoa, a Paravortex like flatworm (4.3%), and a digenean trematode (8%). The monthly mean intensity of the most relevant parasites was between 2.3 and 35.6 for digestive gland intracellular microcolonies of bacteria (IMC), 0-5.1 for intestinal epithelium IMC, 0-2 for branchial IMC and 0 - 48 for intraoocytic microsporidium. The prevalence and the infection intensity were low-to very low, and no World Organisation for Animal Health OIE listed parasite was detected. It is concluded that this is a healthy clam, and no disease risks for the cultivation are visualized at present. However, IMC at high prevalence and intensities of infection could be potentially impactful, and the intraoocytic microsporidian could jeopardize reproduction if present in high intensities of infection.

Nanoemulsified Formulation of Cedrela odorata Essential Oil and Its Larvicidal Effect against Spodoptera frugiperda (J.E. Smith).

Cedrela odorata L. is a plant species from the Meliaceae family that is cultivated for timber production. Although the C. odorata essential oil (EO) contains mainly sesquiterpenes, its insecticidal potential is unknown. The lipophilic properties and high degradation capacity of EOs have limited their application for use in pest control. However, the currently available knowledge on the nanoemulsification of EOs, in addition to the possibility of improving their dispersion, would allow them to prolong their permanence in the field. The objective of the present work was to develop a nanoemulsion of the C. odorata EO and to evaluate its larvicidal activity against Spodoptera frugiperda. The EO was obtained by the hydrodistillation of C. odorata dehydrated leaves, and the nanoemulsion was prepared with non-ionic surfactants (Tween 80 and Span 80) using a combined method of agitation and dispersion with ultrasound. The stability of the nanoemulsion with a droplet diameter of <200 nm was verified in samples stored at 5 °C and 25 °C for 90 days. Both the C. odorata EO and its corresponding nanoemulsion presented lethal properties against S. frugiperda. The results obtained provide guidelines for the use of wood waste to produce sustainable and effective insecticides in the fight against S. frugiperda. In addition, considering that a phytochemical complex mixture allows the simultaneous activation of different action mechanisms, the development of resistance in insects is slower.

Glucoindole alkaloid accumulation induced by yeast extract in Uncaria tomentosa root cultures is involved in defense response.

OBJECTIVE: To evaluate the induction of monoterpenoid indole alkaloids (MIA) and phenolic compound production by yeast extract (YE) and its relationship with defense responses in Uncaria tomentosa (Rubiaceae) root cultures. RESULTS: Root cultures were elicited by YE at three concentrations. The 0.5 mg YE ml-1 treatment did not affect cell viability but increased the hydrogen peroxide concentration by 5.7 times; guaiacol peroxidase activity by twofold; and the glucoindole alkaloid 3α-dihydrocadambine (DHC) content by 2.6 times (to 825.3 ± 27.3 µg g-1). This treatment did not affect the contents of monoterpenoid oxindole alkaloids or chlorogenic acids. In response to 0.5 mg YE ml-1 treatment, the transcript levels of MIA biosynthetic genes, TDC and LAMT, increased 5.4 and 1.9-fold, respectively, that of SGD decreased by 32%, and that of STR did not change. The transcript levels of genes related to phenolic compounds, PAL, CHS and HQT, increased by 1.7, 7.7, and 1.2-fold, respectively. Notably, the transcript levels of Prx1 and Prx encoding class III peroxidases increased by 1.4 and 2.5-fold. CONCLUSION: The YE elicitor induced an antioxidant defense response, increased the transcript levels of genes encoding enzymes related to strictosidine biosynthesis precursors and class III peroxidases, and decreased the transcript level of SGD. Thus, YE could stimulate antifungal DHC production in root cultures of U. tomentosa.

Expression of a codon-optimized ß-glucosidase from Cellulomonas flavigena PR-22 in Saccharomyces cerevisiae for bioethanol production from cellobiose.

Bioethanol is one of the main biofuels produced from the fermentation of saccharified agricultural waste; however, this technology needs to be optimized for profitability. Because the commonly used ethanologenic yeast strains are unable to assimilate cellobiose, several efforts have been made to express cellulose hydrolytic enzymes in these yeasts to produce ethanol from lignocellulose. The C. flavigenabglA gene encoding ß-glucosidase catalytic subunit was optimized for preferential codon usage in S. cerevisiae. The optimized gene, cloned into the episomal vector pRGP-1, was expressed, which led to the secretion of an active ß-glucosidase in transformants of the S. cerevisiae diploid strain 2-24D. The volumetric and specific extracellular enzymatic activities using pNPG as substrate were 155 IU L-1 and 222 IU g-1, respectively, as detected in the supernatant of the cultures of the S. cerevisiae RP2-BGL transformant strain growing in cellobiose (20 g L-1) as the sole carbon source for 48 h. Ethanol production was 5 g L-1 after 96 h of culture, which represented a yield of 0.41 g g-1 of substrate consumed (12 g L-1), equivalent to 76% of the theoretical yield. The S. cerevisiae RP2-BGL strain expressed the ß-glucosidase extracellularly and produced ethanol from cellobiose, which makes this microorganism suitable for application in ethanol production processes with saccharified lignocellulose.

Carotenoid production and gene expression in an astaxanthin-overproducing Xanthophyllomyces dendrorhous mutant strain.

The primary carotenoid synthesized by Xanthophyllomyces dendrorhous is astaxanthin, which is used as a feed additive in aquaculture. Cell growth kinetics and carotenoid production were correlated with the mRNA levels of the idi, crtE, crtYB, crtI, crtS and crtR genes, and the changes in gene sequence between the wild-type and a carotenoid overproducer XR4 mutant strain were identified. At the late stationary phase, the total carotenoid content in XR4 was fivefold higher than that of the wild-type strain. Additionally, the mRNA levels of crtE and crtS increased during the XR4 growth and were three times higher than the wild-type strain in the late stationary phase. Moreover, the nucleotide sequences of crtYB, crtI and crtR exhibited differences between the strains. Both the higher crtE and crtS transcript levels and the crtYB, crtI and crtR mutations can, at least in part, act to up-regulate the carotenoid biosynthesis pathway in the XR4 strain.

Long-term response on growth, antioxidant enzymes, and secondary metabolites in salicylic acid pre-treated Uncaria tomentosa microplants.

OBJECTIVE: To obtain micro propagated Uncaria tomentosa plantlets with enhanced secondary metabolites production, long-term responses to salicylic acid (SA) pre-treatments at 1 and 100 µM were evaluated after propagation of the plantlets in a SA-free medium. RESULTS: SA pre-treatments of single node cuttings OF U. tomentosa produced long-term responses in microplants grown for 75 days in a SA-free medium. Reduction in survival rate, root formation, and stem elongation were observed only with 100 µM SA pre-treatments with respect to the control (0 + DMSO).Both pre-treatments enhanced H2O2 and inhibited superoxide dismutase and catalase activities, while guaiacol peroxidase was increased only with 1 µM SA. Also, both pre-treatments increased total monoterpenoid oxindole alkaloids by ca. 55 % (16.5 mg g(-1) DW), including isopteropodine, speciophylline, mitraphylline, isomitraphylline, rhynchopylline, and isorhynchopylline; and flavonoids by ca. 21 % (914 µg g(-1) DW), whereas phenolic compounds were increased 80 % (599 µg g(-1) DW) at 1 µM and 8.2 % (359 µg g(-1) DW) at 100 µM SA. CONCLUSION: Pre-treatment with 1 µM SA of U.tomentosa microplants preserved the survival rate and increased oxindole alkaloids, flavonoids, and phenolic compounds in correlation with H2O2 and peroxidase activity enhancements, offering biotechnological advantages over non-treated microplants.

Extracellular expression of glucose inhibition-resistant Cellulomonas flavigena PN-120 ß-glucosidase by a diploid strain of Saccharomyces cerevisiae.

The catalytic fraction of the Cellulomonas flavigena PN-120 oligomeric ß-glucosidase (BGLA) was expressed both intra- and extracellularly in a recombinant diploid of Saccharomyces cerevisiae, under limited nutrient conditions. The recombinant enzyme (BGLA¹5) expressed in the supernatant of a rich medium showed 582 IU/L and 99.4 IU/g dry cell, with p-nitrophenyl-ß-D-glucopyranoside as substrate. BGLA¹5 displayed activity against cello-oligosaccharides with 2-5 glucose monomers, demonstrating that the protein is not specific for cellobiose and that the oligomeric structure is not essential for ß-D-1,4-bond hydrolysis. Native ß-glucosidase is inhibited almost completely at 160 mM glucose, thus limiting cellobiose hydrolysis. At 200 mM glucose concentration, BGLA¹5 retained more than 50 % of its maximal activity, and even at 500 mM glucose concentration, more than 30 % of its activity was preserved. Due to these characteristics of BGLA¹5 activity, recombinant S. cerevisiae is able to utilize cellulosic materials (cello-oligosaccharides) to produce bioethanol.

Analysis of proteomic changes in colored mutants of Xanthophyllomyces dendrorhous (Phaffia rhodozyma).

The yeast Xanthophyllomyces dendrorhous synthesizes astaxanthin as its most prevalent xanthophyll derivative. Comparisons between the protein profiles of mutant lines of this yeast can provide insight into the carotenogenic pathway. Differently colored mutants (red, orange, pink, yellow, and white) were obtained from this yeast species, and their protein profiles were determined using two-dimensional polyacrylamide gel electrophoresis (2DE). Individual proteins differentially expressed were identified using mass spectrometry. The red mutants hyperproduced total carotenoids (mainly astaxanthin), while in white and orange mutants, mutagenesis affected the phytoene dehydrogenase activity as indicated by the accumulation of phytoene. Inactivation of astaxanthin synthase after the mutagenic treatment was evident in ß-carotene accumulating mutants. Differences in the proteomic profiles of wild-type X. dendrorhous and its colored mutants were demonstrated using 2DE. Of the total number of spots detected in each gel (297-417), 128 proteins were present in all strains. The red mutant showed the greatest number of matches with respect to the wild type (305 spots), while the white and yellow mutants, which had reduced concentrations of total carotenoids, presented the highest correlation coefficient (0.6) between each other. A number of differentially expressed proteins were sequenced, indicating that tricarboxylic acid cycle and stress response proteins are closely related to the carotenogenic process.

Temperature controlled fluorescence on Au@Ag@PNIPAM-PTEBS microgels: effect of the metal core size on the MEF extension.

In this work, we present a novel method to produce thermoresponsive, monodisperse microgels which display temperature-dependent photoluminescence. The system is based on bimetallic cores of Au@Ag encapsulated within thermoresponsive poly(N-isopropylacrylamide) microgels and coated with a photoluminescent polymer (poly[2-(3-thienyl)ethoxy-4-butylsulfonate] (PTEBS) using the Layer-by-Layer technique. The electromagnetic radiation used to excite the PTEBS induces a local electromagnetic field on the surface of the bimetallic cores that enhances the excitation and emission rates of the PTEBS, yielding a metal enhanced fluorescence (MEF). This effect was studied as a function of the bimetallic core size and the separation distance between the PTEBS and the bimetallic cores. Our results permit evaluation of the effect that the metallic core size of colloidal particles exerts on the MEF for the first time, and prove the relevance of the metallic cores to extend the effect far away from the metallic surface.

Synthesis and evaluation of the novel 2-[¹8F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors.

The 2-[(18)F]fluoro-3-pent-4-yn-1-yloxypyridine ([(18)F]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT1R) blocker losartan was produced via click chemistry linking [(18)F]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT1R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47-65%) in tracer uptake was observed in the kidney, while no difference was observed following AT2R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT1R over AT2R and potential for imaging AT1R using PET.

Induction of Monoterpenoid Oxindole Alkaloids Production and Related Biosynthetic Gene Expression in Response to Signaling Molecules in Hamelia patens Plant Cultures.

Hamelia patens (Rubiaceae), known as firebush, is a source of bioactive monoterpenoid oxindole alkaloids (MOAs) derived from monoterpenoid indole alkaloids (MIAs). With the aim of understanding the regulation of the biosynthesis of these specialized metabolites, micropropagated plants were elicited with jasmonic acid (JA) and salicylic acid (SA). The MOA production and MIA biosynthetic-related gene expression were evaluated over time. The production of MOAs was increased compared to the control up to 2-fold (41.3 mg g DW-1) at 72 h in JA-elicited plants and 2.5-fold (42.4 mg g DW-1) at 120 h in plants elicited with SA. The increment concurs with the increase in the expression levels of the genes HpaLAMT, HpaTDC, HpaSTR, HpaNPF2.9, HpaTHAS1, and HpaTHAS2. Interestingly, it was found that HpaSGD was downregulated in both treatments after 24 h but in the SA treatment at 120 h only was upregulated to 8-fold compared to the control. In this work, we present the results of MOA production in H. patens and discuss how JA and SA might be regulating the central biosynthetic steps that involve HpaSGD and HpaTHAS genes.

Differential alkaloid profile in Uncaria tomentosa micropropagated plantlets and root cultures.

The alkaloids of Uncaria tomentosa micropropagated plantlets and root cultures were isolated and identified by NMR and mass spectrometry. Plantlets yielded pteropodine (1), isopteropodine (2), mitraphylline (3), isomitraphylline (4), uncarine F (5), speciophylline (6), rhynchophylline (7) and isorhynchophylline (8). In plantlets growing under continuous light, tetracyclic alkaloids 7 and 8 decreased from 20 ± 1.8 at 2 months to 2.2 ± 0.33 mg/g dry wt at 6 months, while the pentacyclic alkaloids 1-4 increased from 7.7 ± 1.4 to 15 ± 0.05 mg/g dry wt, supporting their biogenetic conversion. Micropropagated plantlets produced four times more alkaloids (27.6 ± 3.1 mg/g dry wt) than greenhouse plants. Plantlet roots yielded 3, 4, 8 and the glucoindole alkaloids 3α-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria.

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study.

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.

Identification of Putative Candidate Genes from Galphimia spp. Encoding Enzymes of the Galphimines Triterpenoids Synthesis Pathway with Anxiolytic and Sedative Effects.

Galphimia spp. is popularly used in Mexican traditional medicine. Some populations of Galphimia exert anxiolytic and sedative effects due to the presence of the modified triterpenoids galphimines. However, the galphimine synthesis pathway has not yet been elucidated. Hence, in this study, a comparative transcriptome analysis between two contrasting populations of Galphimia spp., a galphimine-producer, and a non-galphimine-producer, is performed using RNA-Seq in the Illumina Next Seq 550 platform to identify putative candidates genes that encode enzymes of this metabolic pathway. Transcriptome functional annotation was performed using the Blast2GO in levels of gene ontology. For differential expression analysis, edgeR, pheatmap, and Genie3 library were used. To validate transcriptome data, qPCR was conducted. In producer and non-producer plants of both populations of Galphimia spp., most of the transcripts were grouped in the Molecular Function level of gene ontology. A total of 680 differentially expressed transcripts between producer and non-producer plants were detected. In galphimine-producer plants, a larger number of highly expressed transcripts related to acyclic and polycyclic terpene synthesis were identified. As putative candidate genes involved in the galphimine synthesis pathway, P450 family members and enzymes with kinase activity were identified.

Fermentation performance of a Mexican native Clavispora lusitaniae strain for xylitol and ethanol production from xylose, glucose and cellobiose.

Lignocellulose hydrolysates are rich in fermentable sugars such as xylose, cellobiose and glucose, with high potential in the biotechnology industry to obtain bioproducts of higher economic value. Thus, it is important to search for and study new yeast strains that co-consume these sugars to achieve better yields and productivity in the processes. The yeast Clavispora lusitaniae CDBB-L-2031, a native strain isolated from mezcal must, was studied under various culture conditions to potentially produce ethanol and xylitol due to its ability to assimilate xylose, cellobiose and glucose. This yeast produced ethanol under microaerobic conditions with yields of 0.451 gethanol/gglucose and 0.344 gethanol/gcellobiose, when grown on 1% glucose or cellobiose, respectively. In mixtures (0.5% each) of glucose:xylose and glucose:xylose:cellobiose the yields were 0.367 gethanol/gGX and 0. 380 gethanol/gGXC, respectively. Likewise, in identical conditions, C. lusitaniae produced xylitol from xylose with a yield of 0.421 gxylitol/gxylose. In 5% glucose or xylose, this yeast had better ethanol and xylitol titers and yields, respectively. However, glucose negatively affected xylitol production in the mixture of both sugars (3% each), producing only ethanol. Xylose reductase (XR) and xylitol dehydrogenase (XDH) activities were evaluated in cultures growing on xylose or glucose, obtaining the highest values in cultures on xylose at 8 h (25.9 and 6.22 mU/mg, respectively). While in glucose cultures, XR and XDH activities were detected once this substrate was consumed (4.06 and 3.32 mU/mg, respectively). Finally, the XYL1 and XYL2 genes encoding xylose reductase and xylitol dehydrogenase, respectively, were up-regulated by xylose, whereas glucose down-regulated their expression.

Production of cellulases and xylanases under catabolic repression conditions from mutant PR-22 of Cellulomonas flavigena.

Derepressed mutant PR-22 was obtained by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutagenic treatment of Cellulomonas flavigena PN-120. This mutant improved its xylanolytic activity from 26.9 to 40 U mg(-1) and cellulolytic activity from 1.9 to 4 U mg(-1); this represented rates almost 2 and 1.5 times higher, respectively, compared to its parent strain growing in sugarcane bagasse. Either glucose or cellobiose was added to cultures of C. flavigena PN-120 and mutant PR-22 induced with sugarcane bagasse in batch culture. The inhibitory effect of glucose on xylanase activity was more noticeable for parent strain PN-120 than for mutant PR-22. When 20 mM glucose was added, the xylanolytic activity decreased 41% compared to the culture grown without glucose in mutant PR-22, whereas in the PN-120 strain the xylanolytic activity decreased by 49% at the same conditions compared to its own control. Addition of 10 and 15 mM of glucose did not adversely affect CMCase activity in PR-22, but glucose at 20 mM inhibited the enzymatic activity by 28%. The CMCase activity of the PN-120 strain was more sensitive to glucose than PR-22, with a reduction of CMCase activity in the range of 20-32%. Cellobiose had a more significant effect on xylanase and CMCase activities than glucose did in the mutant PR-22 and parent strain. Nevertheless, the activities under both conditions were always higher in the mutant PR-22 than in the PN-120 strain. Enzymatic saccharification experiments showed that it is possible to accumulate up to 10 g l(-1) of total soluble sugars from pretreated sugarcane bagasse with the concentrated enzymatic crude extract from mutant PR-22.

Oncologic significance of unexpected osseous foci on FDG-PET without correlative CT abnormalities.

PURPOSE: Our purpose was to explore the clinical significance of unexpected osseous foci on 18F-FDG-PET without correlative CT abnormalities (FWCT) in patients referred for oncologic evaluation. The significance of FDG-avid foci without correlative CT abnormalities has been previously explored in tissues such as breast, lung, liver, and prostate; however, osseous foci without correlative CT abnormalities continue to present challenges in diagnostic interpretations. METHODS: This study is a retrospective review of 120 osseous FWCT, reported in 91 patients, and their corresponding clinical follow-up. We included only patients with at least 6 months of clinical follow-up leading to a final diagnosis, reviewing bone biopsy results, follow-up imaging, and clinical notes. We excluded those patients on active chemotherapy at the time of the scan. For reports describing > 3 foci, we only analyzed the one with highest maximum standardized uptake value (SUVmax). As a measure of uptake intensity, we obtained focus-to-liver ratios (F/L) utilizing their SUVmax and corresponding hepatic 3D SUVmean. RESULTS: Of 91 patients, 74 (81%) had biopsy-confirmed primary malignancies and 17 (19%) had suspicious findings on diagnostic imaging, but no proven primary malignancy. 50 of 120 (42%) osseous foci were malignant and 70 (58%) were benign. 49 of 120 (41%) foci were solitary and 71 (59%) were 0 with other foci (non-solitary). Malignancy resulted from 15/49 (31%) solitary foci and 35/71 (49%) non-solitary foci. Malignant lesions had a mean F/L 2.37 ± 0.397 and benign lesions a mean F/L 1.49 ± 0.169. Osseous malignancy correlated with a higher uptake intensity (Spearman = 0.408; P < 0.01) and was significantly associated with F/L ≥ 2.0 (P < 0.001). Osseous FWCT led to restaging and management modification in 12/91 (13%) patients. CONCLUSION: Osseous FWCT frequently represent early stages of malignancy. A higher index of suspicion is warranted for osseous FWCT associated with underlying myeloproliferative neoplasms, breast and lung cancer, and moderate (F/L 1.0-2.0) or high (F/L > 2.0) uptake intensity. Interpreting physicians encountering these variables can recommend interval follow-up with 18F-FDG-PET/CT or correlation with contrast-enhanced MRI or tissue biopsy. In patients with an altered biodistribution of 18F-FDG in the bone marrow (e.g., recent chemotherapy cycle), follow-up FDG-PET can be obtained at an appropriate time interval following oncologic treatment.