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Adjuvants are often essential additions to vaccines that enhance the activation of innate immune cells, leading to more potent and protective T and B cell responses. Only a few vaccine adjuvants are currently used in approved vaccine formulations in the United States. Combinations of one or more adjuvants have the potential to increase the efficacy of existing and next-generation vaccines. In this study, we investigated how the nontoxic double mutant Escherichia coli heat-labile toxin R192G/L211A (dmLT), when combined with the TLR4 agonist monophosphoryl lipid A (MPL-A), impacted innate and adaptive immune responses to vaccination in mice. We found that the combination of dmLT and MPL-A induced an expansion of Ag-specific, multifaceted Th1/2/17 CD4 T cells higher than that explained by adding responses to either adjuvant alone. Furthermore, we observed more robust activation of primary mouse bone marrow–derived dendritic cells in the combination adjuvant–treated group via engagement of the canonical NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex. This was marked by a multiplicative increase in the secretion of active IL-1β that was independent of classical gasdermin D–mediated pyroptosis. Moreover, the combination adjuvant increased the production of the secondary messengers cAMP and PGE2 in dendritic cells. These results demonstrate how certain adjuvant combinations could be used to potentiate better vaccine responses to combat a variety of pathogens.

SCOPUS: ar.j, info:eu-repo/semantics/published

No abstract available

Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.

In recent years, income inequality in the U.S. has risen to historically high levels. Redistributive policies that differentially benefit lower- versus upper-income households play a significant role in the widening economic gap. A discourse analysis of 284 articles from five major U.S. newspapers was conducted to examine dominant media framing of the Bush administration's welfare reauthorization proposal and the 2003 dividend tax cuts. Guided by critical theory (Delgado & Stefancic, 2001; Wing, 1997), we found that dominant issue frames favored reduced support for progressive welfare policies and increased support for tax cuts. Implications for pursuing an economic justice agenda are discussed.

BACKGROUND The incidence of rectal cancer increases with age, and older patients are more likely to have other chronic conditions that can affect outcome and tolerability of treatment. OBJECTIVE The incidence of rectal cancer increases with age, and older patients are more likely to have other chronic conditions that can affect outcome and tolerability of treatment. METHODS 59 patients aged 75 years and older with stage II-III rectal cancer who were treated during a 3-year period were included in the study. Comorbidities were assessed using the Charlson Comorbidity Index (CCI) and the patients were divided into 2 groups based on their CCI scores: Fit (score of 0-1 points) and Vulnerable (score of greater than or = 2). Primary endpoint was survival at 1 and 3 years. RESULTS The sample included 43 patients (72.9%) in the Fit group and 16 patients (27.1%) in the Vulnerable group. The most common comorbidities were myocardial infarction, diabetes, and chronic lung disease. One-year survival the same between the groups (P = .330), but 3-year survival was lower in the Vulnerable group patients (83.7% vs 56.3%, respectively; P = .040). The rates of neoadjuvant chemo- and radiotherapy use and low anterior resection performance were the same between the groups. Colostomy closure was achieved more frequently in the Fit group compared with the Vulnerable group (83.3% vs 55.6%; P = .083). There was no difference in mean disease-free survival, grade 3-4 toxicity, and dose reduction between the groups. CONCLUSIONS Comorbidity assessment should always be included in standard oncological management of elderly patients. Fit patients can be managed with standard treatment and may bene¦t from a conventional, more aggressive approach in their therapy.

In this article, we draw on critical race theory and critical race feminism to deconstruct contemporary US welfare policy. The political framing of work requirements, single motherhood, and ‘citizenship’ under the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 are used to illustrate the racism, sexism, and classism that pervade current regulations. Drawing on Hurtado’s (1996) conceptualization of the ‘Pendejo Game’, we argue that political elites feign ignorance of poverty and structural inequities to legitimate policies that maintain economic disparities. We conclude with suggestions for disrupting the Pendejo Game and promoting economic justice.

This study examined how 69 low-income women enrolled in an educational training program perceived social class and upward mobility. Participants identified their social class during childhood, their current status, and their anticipated post graduate status. Beliefs about income inequality and attributions for wealth and poverty were also assessed. Respondents expected to achieve middle class status and perceived higher education as a route to upward mobility, although the accessibility of post-secondary programs was questioned. Consistent with previous research involving low-income groups (Bullock, 1999; Kluegel & Smith, 1986), structural attributions for poverty and wealth were favored over individualistic causes. Also, respondents perceived income inequality as unjust. The construction of class identity and implications for class-based mobilization are discussed. It [the American dream] means the opportunity to go as far in life as your abilities will take you. Anyone in America can aspire to be a doctor, a teacher, a police officer or even, as Oprah said, a President. But you can't get any of those important jobs if you don't have the opportunity to acquire the skills you need … . And that's why I believe that the key to the American Dream is education. —————Former President George Herbert Walker Bush, 1997

This study assessed the relationship between attributions for wealth and poverty, beliefs about income inequality and support for progressive and restrictive welfare policies. An updated scale was developed to measure attributions for poverty. “Culture of poverty” items and new structural items loaded strongly, contributing to the development of a more contemporary scale for measuring attributions for poverty. Support for progressive welfare policies was predicted by structural attributions for poverty, dissatisfaction with income inequality, and attributing wealth to privilege, whereas restrictive welfare policies were predicted by individualistic attributions for poverty and wealth. Strategies for building support for progressive welfare policies are discussed.

This study tested the influence of musical style on observers' perceptions of representational and abstract paintings. Participants were thirty-six male and thirty-six female undergraduates who viewed eight paintings under one of three listening conditions: matching, non-matching, or no music. Participants rated each painting on four semantic-differential scales. Mean ratings were compared using MANOVAs. An interaction of painting style and listening condition (Wilks' lambda = .780, p < .05) showed participants' aesthetic experience of viewing the paintings was intensified when the paintings were accompanied by matching music. A main effect for music style (Wilks' lambda = .718, p < .01) showed participants thought all paintings were less active and more beautiful when accompanied by the impressionist music. There were no significant effects for gender.

Ofloxacin, its optical isomers levofloxacin (HR 355, DR-3355) and D-ofloxacin (DR-3354) and ciprofloxacin were administered orally to mice and rats which had systemic and localized infections. Both levofloxacin and ciprofloxacin were equally effective in treating systemic murine infections caused by staphylococci, Enterobacteriaceae or Pseudomonas aeruginosa with ED 50 s ranging from 0.18 to 15.8 mg/kg and 0.42 to 16.3 mg/kg respectively and both these agents were twice as effective as ofloxacin which had an ED 50 0.41 to 39.7 mg/kg. In contrast, D-ofloxacin was either inactive or exhibited only modest chemotherapeutic activity against the staphylococci and the Gram-negative organisms tested. When given to mice to treat staphylococcal abscesses and lung infections due to Klebsiella pneumoniae DT-S levofloxacin was up to four times more effective and produced a more pronounced bactericidal effect against the pathogens in vivo than the reference compounds. Despite possessing a similar, if not lesser, in-vitro activity against the infecting pathogens, levofloxacin was more effective than ofloxacin and ciprofloxacin in rats with localized infections caused by Enterobacteriaceae and P. aeruginosa.

Cefpirome, cefoperazone and ceftazidime were tested for their in-vitro activity against Enterococcus faecalis and methicillin-resistant Staphylococcus aureus (MRSA) isolates. Cefpirome was the most active cephalosporin followed by cefoperazone. Ceftazidime had only very limited activity against these strains. In experiments with cefpirome/vancomycin and cefoperazone/vancomycin combinations, synergy was detected against most MRSA strains and some enterococci. Antagonism did not occur.

The in-vitro activity of cefpirome was compared with other antibiotics against organisms causing sexually transmitted diseases (STD). The excellent activity of cefpirome against Neisseria gonorrhoeae (MIC90 1.0 mg/L), Haemophilus ducreyi (MIC90 0.5 mg/L), and Gardnerella vaginalis (MIC90 1.0 mg/L) suggests that this agent might be useful in the empirical treatment of a variety of venereal diseases.

The pharmacokinetic profile of cefpirome was evaluated in rats and dogs after a single intravenous or intramuscular dose. A two-compartment open model was used for the calculation of the pharmacokinetic parameters for both routes of administration. The elimination half-lives after intravenous and intramuscular administration of 20 mg/kg cefpirome did not differ significantly and ranged from 0.4 h in rats to 1.1 h in dogs. Cefpirome was mainly excreted via the kidneys. After iv or im dosing of the compound, between 80% (dogs) and 90% (rats) was recovered in urine within 24 h. The bioavailability of cefpirome in rats and dogs after both routes of administration was almost identical when calculated either by the AUC or the urinary recovery rates.

Laparoscopic anterior resection with total mesorectal excision for middle and lower third rectal cancer remains a difficult operation, in particular, in male patients with a narrow pelvis and bulky mesentery. In this type of patient, the available staplers do not allow an easy transection of the rectum close to the pelvic floor. A new approach that uses instruments (dilator, obturator, and pursestring anoscope) specifically designed for the technique of stapled hemorrhoidopexy and a common circular stapler can overcome all these issues.

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.

Introduction Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive nonsentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict in-volvement of NSLN in breast cancer patients with positive SLN.

Cefodizime was evaluated for its effect on a number of parameters of leukocyte function in humans. Four healthy volunteers received 2 g i.v. b.i.d. for seven days. Leukocyte activity was measured before, during and after treatment. Using opsonized zymosan as a stimulant, no effect on the respiratory burst of granulocytes was observed. It was found, however, that the lymphocytes in three of the four subjects showed significantly more marked proliferation rates in the mixed lymphocyte reaction after administration of cefodizime than at baseline. The stimulation indices subsequently returned to normal. This pilot study therefore demonstrated that cefodizime has biological response modifying properties in healthy humans.

Two studies examined the effects of stable, partially changed, and completely changed majority and minority positions within a group on perception and evaluation of the group. It was hypothesized that loss of majority position (majority-to-minority change) would have stronger effects than gain of majority position (minority-to-majority change). The hypothesized asymmetrical effect was demonstrated in that loss of majority position decreased perception of group-self similarity, group attraction, and expectations for positive interactions with the group, whereas a corresponding gain of position did not increase them. Thus immediately following changes, the group is especially fragile because disintegrative forces created by the loss of majority position are stronger than integrative forces created by the gain of majority position.

AimsTo determine the eventual advantage of the new 1997 TNM as prognosis predictor for gastric cancer patients submitted to an R0 resection and to compare it with two other lymph-node involvement classifications, the 1990 TNM and the Okusa system.MethodsFrom January 1980 to December 1995, an R0 resection was performed as primary therapy in 275 cases of gastric cancer. These operations consisted of a total or sub-total gastrectomy and of a D2 type lymph-node dissection. Tumour classification was performed according to 1990 and 1997 TNM systems, and to the Okusa lymph node classification. The statistical methods used to evaluate prognostic value were: Kaplan–Meier survival estimates; the log-rank test for univariate analysis; and Cox's model for multivariate analysis.Results.The 1990 TNM showed the best stratification power in univariate analysis. In multivariate analysis, the Okusa classification was identified as the best prognostic index (P

In vitro gamma irradiation of virus-induced (Gross) mouse leukemia cells at doses of 350-1600 rads (1 rad = 0.01 gray) had no effect on their ability to induce leukemia, usually within 2 weeks, after transplantation into syngeneic mice. However, when cells irradiated at doses of 2000-20,000 rads were transplanted, they induced leukemia after a latency period exceeding 2.5 months, similar to the results observed in mice inoculated with filtered mouse leukemia extracts. Similar results were also obtained after irradiation of leukemic cells derived from rats in which leukemia had been induced by rat-adapted mouse leukemia virus. Apparently, gamma irradiation at a dose of, or exceeding, 2000 rads, inhibits the ability of mouse and rat leukemic cells to induce leukemia after transplantation into syngeneic hosts; however, it does not inactivate the virus carried by such cells nor prevent it from inducing leukemia. [In previous experiments, doses of more than 4,500,000 rads were needed to inactivate the passage A (Gross) leukemia virus carried in either mouse or rat leukemic cells.] In vitro gamma irradiation of L2C guinea pig leukemic cells at doses of 750-2500 rads had no apparent effect on their ability to induce leukemia after transplantation effect on their ability to induce leukemia after transplantation into strain 2 guinea pigs. However, irradiation at doses of 3250-20,000 rads inactivated their ability to do so. The morphology of mouse, rat, and guinea pig leukemic cells and the virus particles present in such cells was not affected by irradiation at doses of 20,000 rads.

A protein was isolated from guinea-pig serum which enabled cobra venom factor (VF), in combination with purified C3 proactivator (C3PA) and Mg ++ , to induce turnover of isolated C3. To parallel the terminology for human serum, the protein was designated as factor D of the alternate pathway of complement activation. Purified factor D has a mol. wt of 22, 000 and an s-rate of 2·6. The isoelectric point was determined to be at pH 9·5. Factor D, although resistant to trypsin and hydrazine treatment, was relatively heat labile. It was found that the enzymatic activity directed against C3 was exerted by a trimolecular complex consisting of VF, C3PA and factor D. The existence of such a complex was demonstrated by gel filtration; additional evidence was provided by assembling an active complex on Sepharose-VF. Anti factor D serum blocked the C3 cleaving activity of the complex. Factor D itself was required for the C3 shunt activation induced by inulin, Dextran sulfate, Zymosan or endotoxin.

Desacetyl-cefotaxime, the main metabolite of cefotaxime, possesses a broad antibacterial spectrum. Its activity is lower than that of cefotaxime, but significantly surpasses that of cefazolin against gram-negative bacteria. The beta-lactamase stability of desacetyl-cefotaxime is higher than that of the parent compound. This beta-lactamase stability might be responsible for the synergistic effects of cefotaxime and desacetyl-cefotaxime occasionally seen in in vitro combination studies.

Dinitrophenyl-human serum albumin (DNP-HSA) preparations activate C3 via the alternate pathway of the complement system depending on the grade of DNP substitution. This potency seems to be due to the polyanionic character of DNP-HSA and thus resembles in its behavior other polyanions.

The antibacterial activity of the cephalosporin antibiotic HR 810 was evaluated in comparison with cefoperazone, cefotaxime, ceftazidime, ceftriaxone, latamoxef, gentamicin and amikacin against 1500 clinical isolates. HR 810 is the antibiotic with the broadest antimicrobial spectrum. It is also highly active against isolates of the genera Pseudomonas, Enterobacter, Staphylococcus and enterococci. HR 810 is very stable against hydrolysis by plasmid-coded and chromosomally coded beta-lactamases.

HE movement toward the development of a code of ethics for the nursing profession seems to be at a standstill. A suggested code was presented to the American Nurses' Association in 1926 with the expectation that after further study there might be official approval. This code was never formally adopted, nor is there any evidence that it has been widely discussed among nurses. A Committee on Ethical Standards exists but has found no marked enthusiasm for the code. There is so