A Cohort Study Comparing Pediatric Patients with Overweight and Obesity in the Military Health System.

Background: National Health and Nutrition Examination Survey data from the 1960s to 2010s confirm that pediatric obesity rates are increasing. To assess obesity in the Military Health System (MHS), we evaluated a pediatric cohort's trends in BMI categorization from 2009 to 2016. Methods: We identified two age-based pediatric cohorts in the United States using the MHS Data Repository. We tracked them for BMI from 2009 to 2016. We calculated BMI percentiles and z-scores using validated growth charts, and biologically implausible BMI z-scores were removed from analyses. Using the Stuart-Maxwell test, we assessed the percent change in BMI categorization from 2009 to 2016 and stratified by age group. Results: Our cohort consisted of 130,675 pediatric patients (52.2% males and 47.8% females). The proportion in each BMI categorization changed significantly from 2009 to 2016 in all groups (p < 0.001). Increases in the Overweight and Moderate or Severe Obesity categories were observed in all age groups (2-5, 6-10, and 2-10), and increases in Obese were observed in 6-10-year olds. Most shifts occurred from healthy-weight individuals increasing in BMI category. Conclusions: We observed a significant increase in the proportion of children with overweight and obesity in a nationally representative MHS cohort from 2009 to 2016. The prevalence of obesity, but not overweight, in our cohort mirrored the civilian population. Increasingly heavier MHS and civilian children have implications for our future military force, as they are ineligible for military service if unable to meet weight standards.

LIGHT/TNFSF14 Promotes Osteolytic Bone Metastases in Non-small Cell Lung Cancer Patients.

Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT, is a component of the cytokine network that regulates innate and adaptive immune responses, which promote homeostasis of lymphoid organs, liver, and bone. Metastatic tumors often disrupt the tissue microenvironment, thus altering the homeostasis of the invaded organ; however, the underlying mechanisms required further studies. We investigated the role of LIGHT in osteolytic bone disease induced by metastatic non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC bone metastasis show significantly higher levels of LIGHT expressed in monocytes compared with non-bone metastatic tumors and healthy controls. Serum LIGHT levels were also higher in patients with bone metastases than in controls, suggesting a role for LIGHT in stimulating osteoclast precursors. In bone metastatic patients, we also detected increased RNA expression and serum RANKL levels, thus by adding anti-LIGHT or RANK-fragment crystallizable region (RANK-Fc) in PBMC cultures, a significant inhibition of osteoclastogenesis was observed. To model this observation in mice, we used the mouse lung cancer cell line LLC-1. After intratibial implantation, wild-type mice showed an increased number of osteoclasts but reduced numbers of osteoblasts and decreased osteoid formation. In contrast, Tnfsf14-/- mice showed no significant bone loss or other changes in bone homeostasis associated with this model. These data indicate LIGHT is a key control mechanism for regulating bone homeostasis during metastatic invasion. Thus, LIGHT may be a novel therapeutic target in osteolytic bone metastases. © 2019 American Society for Bone and Mineral Research.

Acute Gastric Volvulus in a 16-Year-Old Male Adolescent: A Case Report.

OBJECTIVE: We described a case of acute mesenteroaxial gastric volvulus in a male adolescent who presented to the pediatric emergency department (ED). CASE: A previously healthy male adolescent presented to the pediatric ED with gradual onset of epigastric pain, emesis, and a soft and nondistended abdomen. After evaluation, management, and resolution of the pain, the patient was discharged home with a primary care follow-up plan. Approximately 5 hours after discharge, the patient returned to the pediatric ED with worsening abdominal pain, the inability to tolerate oral intake, and a firm and distended abdomen. Subsequent evaluation identified an acute mesenteroaxial gastric volvulus. Pediatric surgeons performed an exploratory laparotomy, reduction of the gastric volvulus, and gastropexy, and the patient was discharged after a brief hospitalization. CONCLUSIONS: Acute gastric volvulus can present with symptoms similar to benign abdominal etiologies. Timely diagnosis and intervention are key to improved outcomes for patients.

HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance.

Atorvastatin modulates anti-proliferative and pro-proliferative signals in Her2/neu-positive mammary cancer.

The widely used anticholesterolemic drugs statins decrease the synthesis of cholesterol and the isoprenylation and activity of small G-proteins such as Ras and Rho, the effectors of which are often critical in cell proliferation. Thanks to this property, it has been hypothesized that statins may have anti-tumor activities. We investigated this issue in BALB-neuT mice, which developed Her2/neu-positive mammary cancers with 100% penetrance, and in TUBO cells, a cell line established from these tumors. Contrary to the mammary glands of BALB/c mice, the tumor tissue from BALB-neuT animals had constitutively activated Ras and ERK1/2. These were reduced by the oral administration of atorvastatin, but the statin did not prevent tumor growth in mice nor reduce the proliferation of TUBO cells, although it lowered the activity of mevalonate pathway and Ras/ERK1/2 signaling. By decreasing the mevalonate pathway-derived metabolite geranylgeranyl pyrophosphate and the RhoA/RhoA kinase signaling, atorvastatin activated NF-κB, that sustained cell proliferation. Unexpectedly Her2-positive cells were much more sensitive to the inhibition of RhoA-dependent pathways than to the suppression of Ras-dependent pathways elicited by atorvastatin. Only the simultaneous inhibition of RhoA/RhoA-kinase/NF-κB and Ras/ERK1/2 signaling allowed the statin to decrease tumor cell proliferation. Our study demonstrates that Her2-positive mammary cancers have redundant signals to sustain their proliferation and shows that statins simultaneously reduce the pro-proliferative Ras/ERK1/2 axis and activate the pro-proliferative RhoA/RhoA-kinase/NF-κB axis. The latter event dissipates the antitumor efficacy that may arise from the former one. Only the association of statins and NF-κB-targeted therapies efficiently decreased proliferation of tumor cells.

Purification and characterization of the ouabain-sensitive H+/K+-ATPase from guinea-pig distal colon.

Distal colon absorbs K+ through a Na+-independent, ouabain-sensitive H+/K+-exchange, associated to an apical ouabain-sensitive H+/K+-ATPase. Expression of HKalpha2, gene associated with this ATPase, induces K+-transport mechanisms, whose ouabain susceptibility is inconsistent. Both ouabain-sensitive and ouabain-insensitive K+-ATPase activities have been described in colonocytes. However, native H+/K+-ATPases have not been identified as unique biochemical entities. Herein, a procedure to purify ouabain-sensitive H+/K+-ATPase from guinea-pig distal colon is described. H+/K+-ATPase is Mg2+-dependent and activated by K+, Cs+ and NH4+ but not by Na+ or Li+, independently of K+-accompanying anion. H+/K+-ATPase was inhibited by ouabain and vanadate but insensitive to SCH-28080 and bafilomycin-A. Enzyme was phosphorylated from [32P]-gamma-ATP, forming an acyl-phosphate bond, in an Mg2+-dependent, vanadate-sensitive process. K+ inhibited phosphorylation, effect blocked by ouabain. H+/K+-ATPase is an alpha/beta-heterodimer, whose subunits, identified by Tandem-mass spectrometry, seems to correspond to HKalpha2 and Na+/K+-ATPase beta1-subunit, respectively. Thus, colonic ouabain-sensitive H+/K+-ATPase is a distinctive P-type ATPase.

Prognostic significance of the immunohistochemical localization and serological detection of CA19-9 tumor antigen in colon carcinoma.

PURPOSE: This study was carried out in order to evaluate the expression of CA19-9 antigen in serum and tissue samples of colon cancer patients in relation with other pathological prognostic factors. MATERIALS AND METHODS: 99 patients diagnosed with colon cancer entered the study. The CA19-9 antigen was measured in the serum by ELISA (cut-off value 37 IU/L) and in malignant tissue samples by immunohistochemistry using Mab 192. Seventy-five tissue samples of normal colon served as controls. RESULTS: In cancer cells the CA19-9 antigen was expressed on the cell membrane, in the lumen and in the cytoplasm. The expression of the antigen in the cytoplasm and also the high serum values of the tumor marker correlated well with more differentiated tumors (grade I and II) and with positive lymph nodes cases. There was also a positive correlation between cytoplasmic localization of CA19-9 and high levels in the serum. CONCLUSION: The presence of CA19-9 in the cytoplasm reflects the malignant potential of the colon cancer cell. In less differentiated tumors (grade III) loss of antigenicity is observed. The two methodologies correlate well with each other and their simultaneous application confers to the better use and understanding of this tumor-associated antigen.

Essential oils and hexane extracts from leaves and fruits of Cistus monspeliensis. Cytotoxic activity of ent-13-epi-manoyl oxide and its isomers.

Essential oils and hexane extracts from Cistus monspeliensis L. leaves and fruits were analysed by GC-MS. Manoyl oxide and its isomers, 3 beta-hydroxy-manoyl oxide, 3 beta-hydroxy-13-epi-manoyl oxide, as well as 3 beta-acetoxy-13-epi-manoyl oxide were detected for the first time in C. monspeliensis L. Ent-13-epimanoyl oxide was isolated from the hexane extract of leaves and its structure was determined using spectroscopic methods. In vitro cytotoxic activity of ent-13-epi-manoyl oxide and mixtures of manoyl oxide isomers at 10(-4) M concentrations ranged from 11.1 to 32.2% of the activity for a vinblastine control evaluated against nine leukemic cell lines. The results showed that the manoyl oxide isomer mixtures as well as ent-13-epi-manoyl oxide exhibited a slight growth inhibiting activity.

Prognostic significance of tissue DF3 antigen and CA15-3 tumor marker in primary breast cancer.

The specific monoclonal antibody, DF3, for breast cancer and the corresponding tumor marker CA15-3 were evaluated in 108 patients with primary cancer of the breast. These antigens correlated poorly with the known prognostic parameters. Elevated CA15-3 serum values were associated with the cytoplasmic distribution of the DF3 antigen in the cell. The DF3 distribution pattern and the CA15-3 serum values had prognostic significance for disease-free interval.

Cytotoxicity against human leukemic cell lines, and the activity on the expression of resistance genes of flavonoids from Platanus orientalis.

The cytotoxic activity of three flavonoids, belonging to the kaempherol series, was evaluated against 15 human leukemic cell lines. Flavonoids bearing acyl substituants, 2 and 3, were found to be the most active compounds. A further compound, 1, was examined for its ability to modulate the expression of MDR-1 and GST-pi resistance genes and compounds 2 and 3 for their effect on the uptake of [3H]-thymidine as a marker of DNA synthesis.

Impact of double helical CT and three-dimensional CT arteriography on surgical planning for hepatic transplantation.

BACKGROUND: To assess the impact of preliver transplant double helical computed tomography (DHCT) and three-dimensional computed tomography arteriography (3D-CTA) on surgical planning for hepatic transplantation. METHODS: Vascular findings detected on DHCT/3D-CTAs of 80 patients were shown to the transplant surgeon in a blinded fashion. These findings included hepatic arterial anatomy, diameters of the major vessels that supplied the liver, celiac axis stenosis, splenic artery (SA) aneurysms, and portal vein thrombosis (PVT). The surgeon was asked to state the "planned" surgical approach for each case based on scan findings. These results were subsequently compared with what "actually" occurred at transplantation by review of surgical records. RESULTS: Fifty-five patients had conventional and 25 patients had nonconventional hepatic arterial anatomy. Three patients had PVT, three patients had celiac axis stenosis, and three patients had SA aneurysms. Correlation between the "actual surgical technique" and the "planned surgical approach" was seen in 50/55 (91%) patients with conventional and in 23/25 (92%) patients with nonconventional anatomy. Five patients requiring aortohepatic interposition grafts for arterial anastomoses had either severe celiac axis stenoses or arterial inflow vessels that were 3 mm or smaller. Three patients with PVT underwent successful surgical resection of the thrombosed segment and standard PV anastomoses as planned. Patients with complete replacement of hepatic arterial supply to the superior mesenteric artery required alteration of the sequence of the vascular anastomoses. Patients with SA aneurysms had surgical ligation of the splenic artery. CONCLUSIONS: DHCT/3D-CTA provides noninvasive means to identify findings that have significant impact on surgical planning for hepatic transplantation including celiac axis stenosis, diameter of inflow arterial vessel

Detection and characterization of atherosclerotic fibrous caps with T2-weighted MR.

PURPOSE: We assessed the performance of T2-weighted MR imaging in detecting atherosclerotic fibrous caps and in depicting their integrity. METHODS: Twenty atherosclerotic lesions removed by carotid endarterectomy were imaged on a 1.5-T system using T2-weighted spin-echo sequences. The MR images were reviewed independently by four blinded interpreters for fibrous caps and ruptures. The results obtained from the observers were then graded against histologic findings by using receiver-operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for fibrous cap detection was 0.80, indicating that T2-weighted MR imaging was a good but not definitively diagnostic test for detecting ex vivo fibrous caps. The ROC curve for fibrous cap characterization yielded an area of 0.75, indicating that T2-weighted MR imaging was a fair but not highly diagnostic test for depicting fibrous cap integrity. A definite reading for detection of fibrous caps or rupture was fairly specific (90% and 98%, respectively) but not very sensitive (37% and 12%, respectively). CONCLUSIONS: T2-weighted MR imaging of ex vivo atherosclerotic plaques aided in the detection and evaluation of fibrous caps. In both cases, MR imaging proved more useful for ruling out disease than for confirming its presence.

delta IK17: an antigen expressed on human lymphocytes.

Anti delta IK17 monoclonal antibody was produced by fusing SP2/0/Ag 14 myeloma with spleen cells of BALB/c mice immunized with normal human thymocytes. a delta IK17 antibody recognizes a 44kD cell surface protein detected on human lymphocytes. delta IK17 is expressed on human thymocytes, CD4+ and CD8+ T cell subsets, B, NK cells, as well as on activated cells. The antigen is detected on cells during the early, intermediate and late stages of lymphocyte maturation. In addition, the expression of the antigen is correlated with ontogenesis. A T+ delta IK17+ subpopulation responded poorly to TPA stimulation and provided a better helper signal for PWM-induced IgM synthesis than T+ delta IK17- cells. In addition, different levels of delta IK17 expression were detected in several hematological diseases tested.