Rural barriers to early lung cancer detection: Exploring access to lung cancer screening programs in New Hampshire and Vermont

BackgroundRural populations face many health disadvantages compared to urban areas. There is a critical need to better understand the current lung cancer screening landscape in these communities to identify targeted areas to improve the impact of this proven tool.MethodsData from the County Health Rankings of New Hampshire and Vermont was reviewed for population density, distribution of adult smokers, and level of education compared to the distribution of Lung Cancer Screening Facilities throughout these two states.ResultsScreening programs in southern counties of Vermont with lower levels of education have decreased access. In New Hampshire, there are no programs within 30 miles of the areas with the largest distribution of smokers, and decreased access in some areas with the lowest levels of education.ConclusionsImproving equitable access to high-quality screening services in rural regions and the creation of targeted interventions to address decreased access in areas of high tobacco use and low education is vital to decreasing the incidence of latestage presentations of lung cancer within these populations.     

硒对镉引起的大鼠肝脏超氧阴离子和羟自由基生成的影响

目的研究体外和体内染毒条件下Na2SeO3对CdCl2诱导的大鼠肝组织超氧阴离子(.O2-)和羟自由基(.OH)生成的影响。方法实验动物选用雄性Wistar大鼠。体外实验时,制备肝匀浆,用2.185、8.750和35.000μmol/L的Na2SeO3分别与2.185、8.750和35.000μmol/L的CdCl2联合作用。体内实验时,用3 mg/kg Na2SeO3和1mg/kg CdCl2联合作用,腹腔注射染毒。采用分光光度比色法、荧光法和电子自旋共振测定.O2-和.OH。结果在体外染毒时,2.185和8.750μmol/L的Na2SeO3分别对2.185、8.750和35.000μmol/L的CdCl2诱导的.O2-和.OH的生成具有良好的拮抗作用,35.000μmol/L的Na2SeO3与2.185、8.750和35.000μmol/L的CdCl2联合作用在脂质过氧化、.O2-和.OH的生成方面,没有显示拮抗作用。在体内染毒时,3 mg/kg Na2SeO3和1 mg/kg CdCl2在.O2-和.OH的生成上存在拮抗作用。结论在适宜的剂量条件下,Na2SeO3对CdCl2诱导.O2-和.OH的生成具有一定的拮抗作用。     

Circulating angiogenic and inflammatory cytokine responses to acute aerobic exercise in trained and sedentary young men

Purpose

Endurance exercise training can ameliorate many cardiovascular and metabolic disorders and attenuate responses to inflammatory stimuli. The purpose of this study was to determine whether the angiogenic and pro-inflammatory cytokine response to acute endurance exercise differs between endurance-trained and sedentary young men.

Methods

Ten endurance-trained and ten sedentary healthy young men performed 30 min of treadmill running at 75 % VO_2max with blood sampling before and after exercise. Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble VEGF receptor-1 (sFlt-1) were measured by multiplex ELISA.

Results

Acute exercise increased IL-6 by 165 % (P < 0.05), IL-8 by 32 % (P < 0.05), PlGF by ~16 % (P < 0.05), sFlt-1 by 36 % (P < 0.001), and tended to increase bFGF by ~25 % (P = 0.06) in main effects analyses. TNF-α and VEGF did not change significantly with exercise in either group. Contrary to our hypothesis, there were no significant differences in TNF-α, IL-6, VEGF, bFGF, PlGF, or sFlt-1 between groups before or after acute exercise; however, there was a tendency for IL-8 concentrations to be higher in endurance-trained subjects compared to sedentary subjects (P = 0.06).

Conclusions

These results indicate that 30 min of treadmill running at 75 % VO_2max produces a systemic angiogenic and inflammatory reaction, but endurance exercise training does not appear to significantly alter these responses in healthy young men.     

Serum M65 as a Biomarker for Metastatic Renal Cell Carcinoma

Introduction/BackgroundEffective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC.Patients and MethodsThirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA.ResultsThe median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03).ConclusionTo the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.     

A signal sequence trap based on cell enrichment using anti-CD19 antibody coated magnetic beads

Precursors of many secreted and cell surface proteins contain NH2-terminal signal sequences that lead proteins into the endoplasmic reticulum and to the cell surface. Methods have been developed to clone and identify such proteins by trapping their NH2-terminal signal sequences, so called signal sequence traps. In this study we present an alternative and simplified signal sequence trap based on the combination of a novel vector construct expressing a cDNA library in fusion with a CD19 reporter gene, transfection in mammalian cells and selection of cells expressing trapped signal sequences using magnetic beads. Using this method we have isolated several known and novel factors with signal peptides.     

Evaluation of different types of alginate microcapsules as bioreactors for producing endostatin

The use of nonautologous cell lines producing a therapeutic substance encapsulated within alginate microcapsules could be an alternative way of treating different diseases in a cost-effective way. Malignant brain tumors have been proposed to be treated locally using engineered cells secreting proteins with therapeutic potential encapsulated within alginate microcapsules. Optimization of the alginate capsule bioreactors is needed before this treatment can be a reality. Recently, we have demonstrated that alginate-poly-L-lysine microcapsules made with high-G alginate and a gelled core disintegrated as cells proliferated. In this study we examined the growth and endostatin secretion of 293-EBNA (293 endo) cells encapsulated in six different alginate microcapsules made with native high-G alginate or enzymatically tailored alginate. Stability studies using an osmotic pressure test showed that alginate-poly-L-lysine-alginate microcapsules made with enzymatically tailored alginate was mechanically stronger than alginate capsules made with native high-G alginate. Growth studies showed that the proliferation of 293 endo cells was diminished in microcapsules made with enzymatically tailored alginate and gelled in a barium solution. Secretion of endostatin was detected in lower amounts from the enzymatically tailored alginate microcapsules compared with the native alginate microcapsules. The stability of the alginate microcapsules diminished as the 293 endo cells grew inside the capsules, while empty alginate microcapsules remained stable. By using microcapsules made of fluorescenamine-labeled alginate it was clearly visualized that cells perforated the alginate microcapsules as they grew, destroying the alginate network. Soluble fluorescence-labeled alginate was taken up by the 293 endo cells, while alginate was not detected in live spheroids within fluorescence-labeled alginate microcapsules. Despite that increased stability was achieved by using enzymatically tailored alginate, the cell proliferation destroyed the alginate microcapsules with time. It is therefore necessary to use cell lines that have properties more suited for alginate encapsulation before this technology can be used for therapy.     

Guidelines for Patient-Centered Opioid Prescribing and Optimal FDA-Compliant Disposal of Excess Pills after Inpatient Operation: Prospective Clinical Trial

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Pregnancy and delivery after mid-urethral sling procedures for stress urinary incontinence: case reports and a review of literature

In this article, the effects of pregnancy and delivery on the development of stress urinary incontinence are described with special emphasis on the obstetrical management in women who wish to become pregnant or are pregnant after a preceding mid-urethral sling procedure. Three case histories and a review of literature are presented. Pregnancy after a preceding incontinence operation is rare and makes it quite difficult to formulate guidelines about delivery when a pregnancy occurs. The best advice is to postpone incontinence surgery until after the last pregnancy. There is evidence that an elective caesarean delivery protects against stress urinary incontinence in case of pregnancy after bladder neck suspension. For mid-urethral sling procedures, this evidence is not available. The presented case reports do not clearly demonstrate that caesarean delivery is necessary in case of pregnancy and delivery after a mid-urethral sling procedure. Furthermore, a second mid-urethral sling operation is a minor procedure compared to a caesarean section, and there is evidence that a second mid-urethral sling operation has the same success rate as the first procedure.     

Specific T Helper Cell Requirement for Optimal Induction of Cytotoxic T Lymphocytes against Major Histocompatibility Complex Class II Negative Tumors

This study shows that induction of tumor-specific CD4⁺ T cells by vaccination with a specific viral T helper epitope, contained within a synthetic peptide, results in protective immunity against major histocompatibility complex (MHC) class II negative, virus-induced tumor cells. Protection was also induced against sarcoma induction by acutely transforming retrovirus. In contrast, no protective immunity was induced by vaccination with an unrelated T helper epitope. By cytokine pattern analysis, the induced CD4⁺ T cells were of the T helper cell 1 type. The peptide-specific CD4⁺ T cells did not directly recognize the tumor cells, indicating involvement of cross-priming by tumor-associated antigen-presenting cells. The main effector cells responsible for tumor eradication were identified as CD8⁺ cytotoxic T cells that were found to recognize a recently described immunodominant viral gag-encoded cytotoxic T lymphocyte (CTL) epitope, which is unrelated to the viral env-encoded T helper peptide sequence. Simultaneous vaccination with the tumor-specific T helper and CTL epitopes resulted in strong synergistic protection. These results indicate the crucial role of T helper cells for optimal induction of protective immunity against MHC class II negative tumor cells. Protection is dependent on tumor-specific CTLs in this model system and requires cross-priming of tumor antigens by specialized antigen-presenting cells. Thus, tumor-specific T helper epitopes have to be included in the design of epitope-based vaccines.Adequate T helper cell activation is essential in the initiation of an immune reaction. The inability to control tumor outgrowth can be due to inadequate T helper responses underlying poor tumor-specific immunity. In the cellular immune response, specialized APCs process protein and present antigenic peptide fragments in MHC class II molecules to CD4⁺ T helper lymphocytes. These provide “help” to effector cells via the production of cytokines. Although tumor cells can directly present endogenously processed antigenic peptide in surface MHC class I molecules to CD8⁺ CTL precursors, initiation of tumor-specific CTL responses is likely to involve indirect presentation of tumor antigens by specialized APCs.Evidence for a role of T helper cell–mediated immunity comes from studies with genetically modified tumor cells. CD4⁺ cells can be directly activated by transfection of MHC class II α and β chain genes in mouse tumor cells (1–4). These cells become immunogenic, lose their tumorigenicity, and even induce protection against wild-type MHC class II negative tumors, indicating that direct MHC class II presentation of tumor expressed antigens can induce efficient anti–tumor responses.A central role of CD4⁺ T cells emerged from studies of immunity against FMR (Friend, Moloney, Rauscher)¹ murine leukemia virus (MuLV) type tumors by Greenberg (5). Transfer of purified polyclonal T cells from FBL (Friend MuLV-induced erythroleukemia cell line) vaccinated mice in naive animals can protect these mice against subsequent tumor challenge. Both purified CD4⁺ and CD8⁺ T cells transfer protection to FBL tumors (6). FBL cells do not express MHC class II molecules, but CD4⁺ T cells can protect mice even in the absence of CD8⁺ T cells. In this case, macrophages seem to play an important effector role. CD8⁺ T cells can only be effective if CD4⁺ T cells are present or if exogenous IL-2 is administered. Neither B cells nor NK cells seem to exert a significant role in the FBL sytem. These data suggest involvement of APCs, presenting tumor antigens, and a crucial regulatory role of Ths, which was strongly supported by experiments performed in Friend MuLV env-transgenic mice (7). These mice were rendered tolerant for env-specific Th responses and it was not possible to protect these mice against FBL tumors by vaccination.Immune responsiveness to MuLV is classically regulated by the genes of the H-2 (MHC) complex (8). In particular, the H-2^b haplotype confers resistance, and studies using H-2 recombinant and H-2 mutant mouse strains have mapped the protective effects to the class II I-A^b locus (9, 10). This MHC class II association indicates an important role of T helper cells influencing both CTL activity as well as class switching of antiviral antibodies from IgM to IgG. The H-2 I-A^b phenotype protects against early lymphomagenesis. The identification of two Friend MuLV env-derived epitopes, presented by MHC class II, I-A^b and I-E^b/d, respectively, indicated that tumor-directed T helper immunity is virus specific (11). The few lymphomas that arise in H-2^b mice have abrogated viral antigen or (more rarely) MHC class I expression (12), indicating that CTLs also play a crucial role. CTLs have been proven to recognize viral antigens, both gag and env proteins encode CTL epitopes (13). We have identified a K^b-presented, env-derived Moloney and Rauscher CTL epitope that is subdominant in C57BL/6 mice making use of the D^b mutant BM13 mouse strain (14). The D^b-presented gag-leader (gag-L) derived immunodominant CTL epitope for the FMR type of MuLV has been identified only recently (15).Vaccination with a synthetic peptide comprising a relevant T cell epitope is a powerful method to induce highly specific T cells. Protective vaccination using CTL peptide epitopes has been achieved in pathogenic viral models (16, 17) and tumor models (18–20). Peptide vaccination in IFA led to measurable specific CTL induction and protective immunity against virulent virus or tumor cells. Importantly, peptide vaccination can also be applied succesfully for therapy of established tumors by presenting the peptide in IFA, on RMA-S cells, or on activated dendritic cells (21, 22).We now report the induction of tumor-protective immunity by a single vaccination with a tumor-specific MuLV env-encoded T helper peptide. Strong protection can be achieved against highly aggressive tumor cells that lack MHC class II expression. This indicates the requirement of cross-priming of tumor antigens by local APCs. We show that CD8⁺ T cells, recognizing the gag-L–encoded CTL epitope, are crucial effector cells that are efficiently activated with help from peptide-primed tumor-specific CD4⁺ T cells. Vaccination with a mixture of the T helper peptide and the immunodominant CTL epitope resulted in synergistic, long-term tumor protection.