Patterning microparticles on a template of aggregated cationic dye.

Patternwise aggregation of charged molecules on a surface is potentially a facile approach to generate a template on which to pattern oppositely charged microparticles. We report on the patterning of silica microparticles by a system comprising a photopatternable copolymer and an aggregate forming penta-cationic cyanine dye. A thin film of the copolymer, composed of a molar excess of styrenesulfonic acid oxime ester to cross-linkable glycidyl methacrylate monomomers, was exposed through a mask and neutralized, resulting in a pattern of hydrophobic areas, and where exposed, a hydrophilic cross-linked film with sodium poly(styrenesulfonate) domains. The occurrence and locus of aggregation of an aqueous solution of the dye, applied to the patterned surface was established by absorbance and fluorescence spectroscopy and atomic force microscopy. In exposed areas, dye is imbibed and aggregation induced in sodium styrenesulfonate domains internal to the layer, whereas in the unexposed areas the dye aggregates on the hydrophobic surface. Aqueous anionic silica microparticles applied to the dye treated patterned surface and then rinsed, are retained in the unexposed areas having cationic surface aggregates, but rejected from the exposed areas with internal dye aggregates as these areas retain net negative charge. Mask exposure, absent dye treatment, did not result in patterning as negatively charged microparticles were nowhere retained, and positively charged particles were everywhere retained. The extent of surface coverage by the dye in unexposed areas was deposition time dependent, and ranged from isolated patches covering about 20 percent of the polymer surface to a surface saturated layer, with silica particle patterning robust over the range of dye surface coverages studied. The force requirements to pattern the denser than water silica microparticles are identified, and particle and polymer film surface potentials that meet the critical repulsion force requirement are mapped using an established sphere-to-flat surface electric double layer (EDL) model.

Impact of the COVID-19 Pandemic on the Diagnostic Frequency and Medical Therapies Applied to Subjects With Functional Seizures.

Background and Purposes: The coronavirus 2019 (COVID-19) pandemic was associated with catastrophic consequences and increased psychological distress. However, it is unknown if the pandemic impacted the frequency of functional seizures (FS), a well known manifestation of psychiatric disease. The study objectives are to evaluate FS diagnostic code frequency before and during the COVID-19 pandemic and the therapies applied. We hypothesized that FS frequency would be higher during the pandemic, but that the therapies applied would be similar between the two time periods. Methods: This was a retrospective observational cohort study utilizing the TriNetX ® electronic health record (EHR) database. We included subjects aged 8 to 65 years with a diagnostic code of "conversion disorder with seizures or convulsions." After the query, the study population was divided into 2 groups [pre-COVID-19 (3/1/2018 to 2/29/2020) and COVID-19 (3/1/2020 to 2/28/2022). We analyzed subject demographics, diagnostic, procedure, and medication codes. Results: We included 8680 subjects [5029 (57.9%) pre-COVID-19 and 3651 (42.1%) COVID-19] in this study. There was a higher odds of mental health conditions, anxiolytic prescription, emergency department services, and hospital services, but a lower odds of critical care services during COVID-19. There was no difference in antiepileptic use between the time periods. Conclusions: During the COVID-19 pandemic, a higher odds of anxiolytic use, need for emergency department services, and hospital services was reported. In addition, there was a decreased odds of critical care services. This may reflect a change in how patients with FS were managed during the pandemic.

In silico identification of putative druggable pockets in PRL3, a significant oncology target.

Protein tyrosine phosphatases (PTP) have emerged as targets in diseases characterized by aberrant phosphorylations such as cancers. The activity of the phosphatase of regenerating liver 3, PRL3, has been linked to several oncogenic and metastatic pathways, particularly in breast, ovarian, colorectal, and blood cancers. Development of small molecules that directly target PRL3, however, has been challenging. This is partly due to the lack of structural information on how PRL3 interacts with its inhibitors. Here, computational methods are used to bridge this gap by evaluating the druggability of PRL3. In particular, web-based pocket prediction tools, DoGSite3 and FTMap, were used to identify binding pockets using structures of PRL3 currently available in the Protein Data Bank. Druggability assessment by molecular dynamics simulations with probes was also performed to validate these results and to predict the strength of binding in the identified pockets. While several druggable pockets were identified, those in the closed conformation show more promise given their volume and depth. These two pockets flank the active site loops and roughly correspond to pockets predicted by molecular docking in previous papers. Notably, druggability simulations predict the possibility of low nanomolar affinity inhibitors in these sites implying the potential to identify highly potent small molecule inhibitors for PRL3. Putative pockets identified here can be leveraged for high-throughput virtual screening to further accelerate the drug discovery against PRL3 and development of PRL3-directed therapeutics.

A Comparison of Dietary Patterns and Factors Influencing Food Choice among Ethnic Groups Living in One Locality: A Systematic Review.

Globally, the number of minority ethnic groups in high-income countries is increasing. However, despite this demographic change, most national food consumption surveys are not representative of ethnically diverse populations. In consequence, many ethnic minorities' dietary intakes are underreported, meaning that accurate analysis of food intake and nutrient status among these groups is not possible. This systematic review aims to address these gaps and understand differences in dietary intakes and influencers of dietary habits of ethnic groups worldwide. A systematic search was conducted through three databases (Pubmed, Web of Science and Scopus) and manual searches, generating n = 56,647 results. A final search of these databases was completed on 13 September 2021, resulting in a total of 49 studies being included in this review. Overall, food group intakes-particularly fruit, vegetable and fish intake-and diet quality scores were seen to differ between ethnicities. Overall Black/African American groups were reported to be among the poorest consumers of fruit and vegetables, whilst Asian groups achieved high diet quality scores due to higher fish intakes and lower fat intakes compared to other groups. Limited data investigated how nutrient intakes, dietary and meal patterns compared between groups, meaning that not all aspects of dietary intake could be compared. Socioeconomic status and food availability appeared to be associated with food choice of ethnic groups, however, confounding factors should be considered more closely. Future work should focus on comparing nutrient intakes and meal patterns between ethnicities and investigate potential targeted interventions which may support adherence to food-based dietary guidelines by all ethnic groups.

Laparoscopic cholecystectomy for mild acute gallstone pancreatitis-indication itself is a good predictor of (minimal) intraoperative difficulty-a retrospective cohort study.

Objectives: The literature predicting difficulties during Laparoscopic Cholecystectomy (LC) for Acute Gallstone Pancreatitis (AGP) is mainly focused on the timing of operation. In our experience, LC for AGP is rarely difficult irrespective of the timing of operation. The aim of this study was to assess intra- operative difficulties in mild AGP patients to verify this observation. Material and Methods: A retrospective analysis of all consecutive patients who underwent LC for mild AGP between 2014 and 2018 in a single centre was performed. Patients with known alcohol abuse, post-endoscopic retrograde cholangiopancreaticography (ERCP) induced pancreatitis, and those with chronic pancreatitis were excluded. Univariate weighted analysis was performed with 11 factors, with a linear threshold boundary defined as the mean distance between the four degrees of difficulty (DoD 1-4). Results: Ninety-six patients (Male= 33, median age= 56; Female= 63, median age= 52) were analysed. Majority of the patients were an ASA of two (n= 50; 52%) with a median BMI of 28 (range 18-50). Five procedures were technically difficult (DoD≥ 3) and only one procedure was converted to open operation. Univariate analysis showed that duration of pancreatitis >6 days (p= 0.002) and evidence of acute cholecystitis (p <0.05) are associated with a difficult LC (DoD≥ 3). The rest of the factors did not influence DoD. Conclusion: Based on this result, we suggest that LC for mild AGP is rarely difficult, and this finding can be used in practice for selecting these patients for training lists.

The Impact of Lockdown During the COVID-19 Outbreak on Dietary Habits in Various Population Groups: A Scoping Review.

Background: Since the beginning of the COVID-19 pandemic, access to fresh food has been restricted, and people are spending more time inside and have limited their physical activity. However, more time at home may have resulted in some positive habits including an increase in cooking. The aim of this review was to assess dietary changes during the first lockdown. Themes and patterns were considered and associations with other lifestyle factors were assessed. Methods: Between June and July 2020, the PubMed, Google Scholar, and Science Direct databases were searched, and results were screened for eligibility based on title, abstract, and full text. The inclusion criteria of this search included: papers published (or in pre-print) in the year 2020; studies that investigated the impact of COVID-19 lockdown on diet; papers published in English. Exclusion criteria were as follows: papers examining dietary changes in those following a structured diet based on diagnosed conditions or dietetic advice; literature, systematic, or narrative studies reviewing previous research. Researchers agreed on the study characteristics for extraction from final papers. Results: Four thousand three hundred and twenty-two studies were originally considered with 23 final full-text papers included. Four themes were identified: dietary patterns, dietary habits (favorable), dietary habits (unfavorable), and other (includes physical activity levels, weight gain). A total of 10 studies reported an increase in the number of snacks consumed, while six studies found that participants increased their meal number and frequency during quarantine. Eleven studies reported favorable changes in dietary habits with an increase in fresh produce and home cooking and reductions in comfort food and alcohol consumption. However, nine studies found a reduction in fresh produce, with a further six reporting an increase in comfort foods including sweets, fried food, snack foods, and processed foods. Two studies reported an increase in alcohol consumption. In eight studies participants reported weight gain with seven studies reporting a reduction in physical exercise. Conclusion: The effect of COVID-19 lockdown both negatively and positively impacted dietary practices throughout Europe and globally, and negative diet habits were associated with other poor lifestyle outcomes including weight gain, mental health issues, and limited physical activity. Both in the short term and if sustained in the long term, these changes may have significant impacts on the health of the population.

Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae.

Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMPhi). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMPhi (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMPhi gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-kappaB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

Safety and Efficacy of Day-case Percutaneous Nephrolithotomy: A Systematic Review from European Society of Uro-technology.

CONTEXT: Day case or ambulatory percutaneous nephrolithotomy (PCNL) has risen over the last few years with the aim of discharging patients within 24h. OBJECTIVE: We perform a systematic review of literature to evaluate the outcomes of day-case PCNL surgery. EVIDENCE ACQUISITION: A Cochrane style search was performed and the following bibliographic databases were accessed: PubMed, Science Direct, Scopus, and Web of Science. This was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. All studies in the English language reporting on PCNL patients discharged within 24h were included. EVIDENCE SYNTHESIS: Based on the literature search of 97 articles, nine (502 patients) met the inclusion criteria (mean age: 47 yr), with a mean stone size of 20.5mm. The mean operating time was 66min, and over a mean hospital stay of 17.5h, the stone-free rate was 95%. The overall complication rate was 13.5%; the vast majority of these complications were Clavien I-II complications, with a readmission rate of 3%. CONCLUSIONS: Day-case PCNL is a safe and feasible strategy in carefully selected cases. However, for its success, detailed planning and adherence to surgical protocol are paramount with strict criteria for inpatient admission and a thorough follow-up plan. PATIENT SUMMARY: Day-case percutaneous nephrolithotomy procedure seems to be a safe procedure with good outcomes, and low risk of complications and readmissions. Detailed preoperative protocol and planning are paramount, with indications for inpatient admission as well as a thorough follow-up plan.

Role of Minimally Invasive Percutaneous Nephrolithotomy Techniques-Micro and Ultra-Mini PCNL (<15F) in the Pediatric Population: A Systematic Review.

INTRODUCTION: Management of pediatric stone disease is challenging, with standard percutaneous nephrolithotomy (PCNL) having a good stone-free rate (SFR), but with associated high complication rates. Miniaturization of this technique has led to the rise of minimally invasive PCNL techniques such as micro (<10F) and ultra-mini (<15F) PCNL procedures. Our objective was to perform a systematic review of the literature to evaluate the success and complication rates of minimally invasive PCNL techniques in the pediatric age group (<18 years). METHODS: A Cochrane style search was performed and the following bibliographic databases were accessed: PubMed, Science direct, Scopus, and Web of Science. This was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 14 studies (456 patients), including 8 on micro-PCNL (m-PCNL, n = 233) and 6 on ultra-mini PCNL (UMP, n = 223), were included. Mean stone size ranged from 12-16.5 mm (m-PCNL) and 12-41 mm (UMP), and the overall SFR ranged from 80% to 100% (m-PCNL) and 85% to 100% (UMP). The overall complication rates for all studies were 11.2%, which was slightly higher for UMP (13.9%). Postoperative renal colic or fragment obstruction was only seen in m-PCNL, but there was a statistically significant rate of extravasation or renal pelvicaliceal perforation and hematuria for UMP compared with m-PCNL. CONCLUSION: Miniaturized PCNL techniques can deliver high SFRs with a small risk of Clavien I/II complications. The size of tract seems to influence the nature of complications, with higher hematuria and renal extravasation with increasing tract size.

Deletion of TNF-like weak inducer of apoptosis (TWEAK) protects mice from adipose and systemic impacts of severe obesity.

OBJECTIVE: To investigate the role of TNF-like weak inducer of apoptosis (TWEAK) in pathological adipose tissue (AT) remodeling and complications of obesity. METHODS: Wild type (WT) and TWEAK knockout (KO) mice were fed normal diet (ND) or a high fat diet (HFD) for up to 17 weeks. Adipocyte death was induced using an established transgenic mouse model of inducible adipocyte apoptosis (FAT-ATTAC). Metabolic, biochemical, histologic, and flow cytometric analyses were performed. RESULTS: TWEAK and its receptor, fibroblast growth factor-inducible molecule 14 (Fn14) were upregulated in gonadal (g)AT of WT mice after HFD week 4 and 24 h after induction of adipocyte apoptosis. Phenotypes of KO and WT mouse were indistinguishable through HFD week 8. However, at week 17 obese KO mice had ∼30% larger gAT adipocytes and gAT mass than WT mice, coincident with reduced adipocyte death, enhanced insulin signaling, Th2/M2 immune skewing, fewer thick collagen fibers, and altered expression of extracellular matrix constituents and modulators that is consistent with reduced fibrosis and larger adipocytes. KO mice were less steatotic and became more insulin sensitive and glucose tolerant than WT mice after HFD week 12. CONCLUSION: TWEAK constrains "healthy" gAT expansion and promotes metabolic complications in severe obesity.

Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity.

Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (≈ 31 g) became fatter than SHM mice (≈ 26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MΦ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (-20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-γ (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity.

Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer.

Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3ß), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3ß was elevated in the colonic mucosa of obese mice (P<.02). Moreover, ß-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer.

T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice.

The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4-22 weeks of a high-fat diet (HFD (60% energy)). By week 6, eAT mass and stromal vascular cell (SVC) number increased threefold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3(+) SVCs or in gene expression of CD3, interferon-γ (IFN-γ), or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c(+) macrophages (MΦ) were enriched sixfold by week 8 (P < 0.01). SVC enrichment for T cells (predominantly CD4(+) and CD8(+)) and elevated IFN-γ and RANTES gene expression were detected by 20-22 weeks of HFD (P < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T-cell priming earlier in the obesity time course is suggested by (i) elevated (fivefold) interleukin-12 (IL-12)p40 gene expression in eAT by week 12 (P ≤ 0.01) and (ii) greater IFN-γ secretion from phorbol myristate acetate (PMA)/ionophore-stimulated eAT explants at week 6 (onefold, P = 0.08) and week 12 (fivefold, P < 0.001). In conclusion, T-cell enrichment and IFN-γ gene induction occur subsequent to AT macrophage (ATMΦ) recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFN-γ production suggests the contribution of CD4(+) and/or CD8(+) effectors to cell-mediated immune responses promoting HFD-induced AT inflammation and IR.

Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet--induced obesity in mice.

OBJECTIVE: To identify, localize, and determine M1/M2 polarization of epidydimal adipose tissue (eAT) macrophages (Phis) during high-fat diet (HFD)-induced obesity. RESEARCH DESIGN AND METHODS: Male C57BL/6 mice were fed an HFD (60% fat kcal) or low-fat diet (LFD) (10% fat kcal) for 8 or 12 weeks. eATMPhis (F4/80(+) cells) were characterized by in vivo fluorescent labeling, immunohistochemistry, fluorescence-activated cell sorting, and quantitative PCR. RESULTS: Recruited interstitial macrophage galactose-type C-type lectin (MGL)1(+)/CD11c(-) and crown-like structure-associated MGL1(-)/CD11c(+) and MGL1(med)/CD11c(+) eATMPhis were identified after 8 weeks of HFD. MGL1(med)/CD11c(+) cells comprised approximately 65% of CD11c(+) eATMPhis. CD11c(+) eATMPhis expressed a mixed M1/M2 profile, with some M1 transcripts upregulated (IL-12p40 and IL-1beta), others downregulated (iNOS, caspase-1, MCP-1, and CD86), and multiple M2 and matrix remodeling transcripts upregulated (arginase-1, IL-1Ra, MMP-12, ADAM8, VEGF, and Clec-7a). At HFD week 12, each eATMPhi subtype displayed an enhanced M2 phenotype as compared with HFD week 8. CD11c(+) subtypes downregulated IL-1beta and genes mediating antigen presentation (I-a, CD80) and upregulated the M2 hallmark Ym-1 and genes promoting oxidative metabolism (PGC-1alpha) and adipogenesis (MMP-2). MGL1(med)/CD11c(+) eATMPhis upregulated additional M2 genes (IL-13, SPHK1, CD163, LYVE-1, and PPAR-alpha). MGL1(med)/CD11c(+) ATMPhis expressing elevated PGC-1alpha, PPAR-alpha, and Ym-1 transcripts were selectively enriched in eAT of obese mice fed pioglitazone for 6 days, confirming the M2 features of the MGL1(med)/CD11c(+) eATMPhi transcriptional profile and implicating PPAR activation in its elicitation. CONCLUSIONS: These results 1) redefine the phenotypic potential of CD11c(+) eATMPhis and 2) suggest previously unappreciated phenotypic and functional commonality between murine and human ATMPhis in the development of obesity and its complications.

Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylase genes with biochemical measures of vitamin K status.

Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n=416, 60-80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874+/-0.092 versus CG/CC 0.598+/- 0.044; p=0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phylloquinone geometric means: 0.579+/-0.045 versus 0.762+/-0.057; p=0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.