The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although, TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

Electrochemical, mechanistic, and DFT studies of amine derived diphosphines containing Ru(II)-cymene complexes with potent in vitro cytotoxic activity against HeLa and triple-negative breast cancer cells MDA-MB-231.

Complexes with general formula [RuCl(η6-p-cymene)(P-NR-P)]X (R = CH2Py (Py = pyridine) - [1a]+, CH2Ph (Ph = phenyl) - [1b]+, Ph - [1c] and p-tol (p-tol = p-tolyl) - [1d]+; X = PF6- or BF4-) were evaluated as cytotoxic agents against two cancer cell lines (HeLa and MDA-MB-231). All metal complexes are active in the range of concentrations tested (up to 100 µmol L-1). The IC50 (µmol L-1) values for the metal complexes are lower than that found for cisplatin. The activities are up to 6- and 15-fold higher than cisplatin for HeLa and MDA-MB-231 cancer cell lines, respectively. Studies of DNA binding and DNA cleavage were performed. DNA binding studies revealed a modest hypochromic shift in the metal complexes electronic spectra, indicating a weak interaction with Kb values in the range of 1.7 × 103-1.6 × 104. Although the cleavage tests revealed that in the dark DNA is not a biological target for these metal complexes, upon blue light irradiation they are activated causing DNA cleavage. Electrochemical studies showed the presence of two independent redox processes, one attributed to the oxidation process of Ru2+ → Ru3+ (EC process) and the other one to the reduction of Ru2+ → Ru1+, which is further reduced to Ru0 (ECE mechanism). In both processes, coupled chemical reactions were observed. DFT calculations were performed to support the electrochemical/chemical behavior of the complexes. The reactivity of complex [1b]BF4 with CH3CN was evaluated and two complexes were isolated [2b]BF4 and [3b]BF4. The complex mer-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4 ([2b]BF4) was isolated after refluxing the precursor [1b]BF4 in CH3CN. Isomerization of [2b]BF4 in CH3CN resulted in the formation of fac-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4. An attempt to isolate the fac-isomer by adding diethyl ether was unsuccessful, and the complex [3b]BF4 was observed as the major component. The complex [Ru2(µ-Cl3)(CH3CN)2(P-NCH2Ph-P)2]BF4 ([3b]BF4) proved to be very stable and can be obtained from both the mer- and the fac-isomers. The molecular structures of [1b]BF4 and [3b]BF4 were solved by single-crystal X-ray diffraction.

Bacterial Therapy of Cancer: Promises, Limitations, and Insights for Future Directions.

Spontaneous tumors regression has been associated with microbial infection for 100s of years and inspired the use of bacteria for anticancer therapy. Dr. William B. Coley (1862-1936), a bone- sarcoma surgeon, was a pioneer in treating his patients with both live bacterial-based and mixture of heat-killed bacteria known as "Coley's toxins." Unfortunately, Coley was forced to stop his work which interrupted this field for about half a century. Currently, several species of bacteria are being developed against cancer. The bacterial species, their genetic background and their infectious behavior within the tumor microenvironment are thought to be relevant factors in determining their anti-tumor effectiveness in vivo. In this perspective article we will update the most promising results achieved using bacterial therapy (alone or combined with other strategies) in clinically-relevant animal models of cancer and critically discuss the impact of the bacterial variants, route of administration and mechanisms of bacteria-cancer-cell interaction. We will also discuss strategies to apply this information using modern mouse models, molecular biology, genetics and imaging for future bacterial therapy of cancer patients.

[Hand fine motor skills and use of both hand and arm in subjects after a stroke: a systematic review]. / Herramientas de evaluacion del uso fino de la mano y uso de la mano y el brazo en sujetos con secuela de ictus: revision sistematica.

INTRODUCTION: In clinical practice it is important to be able to assess the function of the upper limb of the patient who has suffered a stroke. There is currently no systemic review that could identify assessment tools for the 'fine use of the hand' and 'use of both hand and arm'. AIMS: Primary, to identify observational tools which can assess the fine use of the hand and the use of both hand and arm in patients with stroke sequels. Secondary, to analyze the bias risk in the included articles, describing and categorizing the clinical utility, validity and reliability. PATIENTS AND METHODS: A search was carried in Medline, LILACS, SciELO and Open Grey, which included articles published until October 2015. Studies that validate assessing tools of the upper limb in subjects with a stroke sequel which evaluate the fine use of the hand and the use of both hand and arm were included. RESULTS: Eleven tools in evaluate observational haven been selected, which assess the fine use of the hand and the use of hand and arm. CONCLUSIONS: In every case both validity and reliability have been reported, but clinical utility has been less considered for assessment. The studies that researched these tools showed a high risk of bias in their development. ARAT-19 showed a lower bias risk, but when it has to do with applicability and the reference trial is taken into account, the level of concern is high.

TITLE: Herramientas de evaluacion del uso fino de la mano y uso de la mano y el brazo en sujetos con secuela de ictus: revision sistematica.Introduccion. En la practica clinica resulta importante poder evaluar la funcion de la extremidad superior paretica del paciente que ha sufrido un ictus. No hay una revision sistematica que identifique herramientas de evaluacion del 'uso fino de la mano' o el 'uso de la mano y el brazo'. Objetivos. Como objetivo primario, identificar las herramientas observacionales que evaluan el uso fino de la mano o el uso de la mano y el brazo en pacientes con secuela de ictus. Secundariamente, analizar el riesgo de sesgo de los articulos incluidos, describir y categorizar la validez, fiabilidad y utilidad clinica. Pacientes y metodos. Se realizo una busqueda en Medline, LILACS, SciELO y Open Grey hasta octubre de 2015. Se incluyeron estudios de validacion de herramientas de evaluacion del miembro superior en sujetos con secuela de ictus, que evaluen el uso fino de la mano o el uso de la mano y el brazo. Resultados. Se han seleccionado 11 herramientas que evaluan el uso fino de la mano y el uso de la mano y el brazo. Conclusiones. Si bien se comunicaron la fiabilidad, la validez y la utilidad clinica, esta ultima fue menos evaluada. Los estudios que investigaron estas herramientas presentaron alto riesgo de sesgo, en particular en la eleccion de la prueba de referencia. La herramienta ARAT-19 fue la que presento un menor riesgo de sesgo, pero cuando se evaluo la aplicabilidad, esta presento una preocupacion alta para la prueba de referencia.

Physical Activity Levels in a Community Lifestyle Intervention: A Randomized Trial.

BACKGROUND: A behavioral lifestyle intervention program with goals of increasing physical activity (PA) and losing weight was shown to be efficacious for preventing type 2 diabetes and decreasing risk for cardiovascular disease in the U.S. Diabetes Prevention Program (DPP). Modified versions of the DPP lifestyle intervention are being translated into diverse community settings and have been successful in decreasing weight and improving metabolic markers. However, comprehensive evaluations of PA levels within these community translation intervention efforts are rare. PURPOSE: To evaluate the effectiveness of a DPP-based community lifestyle intervention for improving PA levels. METHODS: 223 overweight adults at-risk for type 2 diabetes and/or cardiovascular disease were randomized (immediate or 6-month delayed-start) to a 12-month DPP-based lifestyle intervention. Past-month PA level was assessed at baseline and post-intervention with the Modifiable Activity Questionnaire. Simple and mixed-effects regression models were used to determine changes in PA level between and within groups over time. RESULTS: The between-group mean difference for change in PA levels from baseline to 6 months indicated significantly greater improvement in the intervention compared to the delayed-start group [+6.72 (SE=3.01) MET-hrs/week; p=0.03]. Examining combined within-group change from baseline to post-intervention, mean PA levels significantly increased by +14.69 (SE=1.43) and +9.50 (SE= 1.40) MET-hrs/week at 6 and 12 months post-intervention, respectively. This PA change offset to approximately +10 MET-hrs/week at both 6 and 12 months after adjusting for baseline PA level and season (all; p<0.01). Other than season, sex impacted on change in PA level. CONCLUSIONS: This community-based lifestyle intervention significantly increased PA levels among overweight adults at risk for type 2 diabetes and cardiovascular disease, even after adjusting for key variables. CLINICALTRIALSGOV IDENTIFIER: NCT01050205.

Experimental and theoretical studies of copper complexes with isomeric dipeptides as novel candidates against breast cancer.

In the search for new cytotoxic drugs, two copper complexes with isomeric dipeptides (Ala-Phe and Phe-Ala) were developed in order to determine the influence of their different structures in the modulation of the chemical, biochemical and biological properties. Spectroscopic, voltammetric and equilibrium studies were performed providing information about the chemical properties. The superoxide dismutase (SOD) activity was studied and showed differences of IC50 for both Cu-Ala-Phe (IC50=4.5) and Cu-Phe-Ala (IC50=45). The computational results permitted to explain this behavior proposing that it is feasible that the O2- anion is attracted straight to the positive zone in Cu-Ala-Phe whereas for Cu-Phe-Ala this phenomenon would happen to a smaller extent. Confirming our previous studies, both complexes interacted with DNA. Molecular docking studies showed that the position of the phenyl ring modulates the complex-DNA affinity and in Cu-Ala-Phe the docked conformation allows the copper ion to face the DNA basis, giving rise to a more stable complex-DNA adduct than for Cu-Phe-Ala. In spite of the fact that Atomic Force Microscopy showed plasmid compactation and aggregation for both complexes, the image showed softer changes in the case of Cu-Ala-Phe in comparison with those produced by Cu-Phe-Ala. In order to evaluate the effect of Cu-Ala-Phe and Cu-Phe-Ala complexes against tumor cells, we have employed three aggressive metastatic breast adenocarcinoma cellular models, derived from human (MDA-MB-231 and MCF-7) and mouse (4T1) spontaneous tumors. These experiments showed that both Cu-dipeptide complexes have a similar cytotoxic effect against breast cancer cells, and lower toxicity against BJ non-tumor cells in comparison to Cisplatin.

[Peripheral nerve stimulation effectiveness in the upper limb function recovery of patients with a stroke sequel: systematic review and meta-analysis]. / Efectividad de la estimulacion nerviosa periferica en la recuperacion de la funcion del miembro superior en sujetos con secuela de ictus: revision sistematica y metaanalisis.

INTRODUCTION: In 30-66% of the cases, people who survive a stroke suffer from an affected non functional upper limb. Somatosensory stimulation might positively influence the muscular activity of patients with motor deficiencies caused by a stroke. AIM: To carry out a systematic review and a meta-analysis of the effectiveness of peripheral nerve stimulation (PNS) use in the improvement of the plegic/paretic upper limb function in patients with a stroke sequel. SUBJECTS AND METHODS: Randomized and non randomized clinically controlled tests and crossover studies published until November 2014 in Medline electronic database, Cochrane Central Register of Controlled Trials, LILACS, SciELO and Open Grey were included. Studies at high risk of bias were excluded. Two independent researchers assessed the studies' eligibility criteria and retrieved and analyzed all data. RESULTS: A total of 1,967 studies were found, five of them were included for data retrieval and analysis, using a risk of bias fashion of 6/10 at the PEDro scale. 224 patients were included, 95 of them received PNS in multiple modalities and 129 received other interventions as a control group. CONCLUSION: The analyzed data suggest that the function of the plegic/paretic upper limb improves after the application of PNS either with or without functional training. On the other hand, the meta-analysis result indicates that there is still insufficient evidence to guarantee the effectiveness of PNS use for the recovery of the plegic/paretic upper limb function in patients with a stroke sequel.

TITLE: Efectividad de la estimulacion nerviosa periferica en la recuperacion de la funcion del miembro superior en sujetos con secuela de ictus: revision sistematica y metaanalisis.Introduccion. Un 30-66% de las personas que sobreviven a un ictus queda con un miembro superior afectado. La estimulacion nerviosa periferica (ENP) influiria positivamente en la actividad muscular de pacientes con deficits motores secundarios a un ictus. Objetivo. Realizar una revision sistematica y un metaanalisis acerca de la efectividad de la aplicacion de la ENP en la recuperacion de la funcion del miembro superior plejico/paretico en sujetos con secuela de ictus. Sujetos y metodos. Se incluyeron ensayos clinicos controlados aleatorizados y no aleatorizados, y estudios cruzados, publicados hasta noviembre de 2014 en Medline, Cochrane Central Register of Controlled Trials, LILACS, SciELO y Open Grey. Se excluyeron articulos con alto riesgo de sesgo. Dos investigadores independientes evaluaron la elegibilidad de los estudios, y realizaron la extraccion y analisis de los datos. Resultados. Se encontraron 1.967 articulos, de los cuales se incluyeron cinco para la extraccion de datos y analisis, con una moda de riesgo de sesgo de 6/10 en la escala PEDro. Se incluyeron en total 224 sujetos, de los cuales 95 recibieron ENP en diversas modalidades y 129 recibieron otras intervenciones como grupo control. Conclusion. Los datos analizados sugieren que la funcion del miembro superior plejico/paretico mejora tras la aplicacion de ENP en conjunto o no con entrenamiento funcional. Sin embargo, el resultado del metaanalisis indica que aun no se dispone de evidencia suficiente para avalar la efectividad del uso de ENP para la recuperacion de la funcion del miembro superior plejico/paretico en sujetos con secuela de ictus.

Determination of Plasmid Segregational Stability in a Growing Bacterial Population.

Bacterial plasmids are extensively used as cloning vectors for a number of genes for academic and commercial purposes. Moreover, attenuated bacteria carrying recombinant plasmids expressing genes with anti-tumor activity have shown promising therapeutic results in animal models of cancer. Equitable plasmid distribution between daughter cells during cell division, i.e., plasmid segregational stability, depends on many factors, including the plasmid copy number, its replication mechanism, the levels of recombinant gene expression, the type of bacterial host, and the metabolic burden associated with all these factors. Plasmid vectors usually code for antibiotic-resistant functions, and, in order to enrich the culture with bacteria containing plasmids, antibiotic selective pressure is commonly used to eliminate plasmid-free segregants from the growing population. However, administration of antibiotics can be inconvenient for many industrial and therapeutic applications. Extensive ongoing research is being carried out to develop stably-inherited plasmid vectors. Here, I present an easy and precise method for determining the kinetics of plasmid loss or maintenance for every ten generations of bacterial growth in culture.

Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice.

BACKGROUND: Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. METHODS: 2×10(8) particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10(7) units of an aroC (-) Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. RESULTS: SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90% of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor; however 100% of them could be totally cured by applying the same neoadjuvant combined regimen. To our knowledge, these are the most encouraging results obtained to date in a post-operatory setting using the highly aggressive 4T1 animal model. CONCLUSIONS: SFV-IL-12-based gene therapy combined with Salmonella LVR01 neoadjuvant administration has a synergic antitumor effect and may be a promising therapeutic option to prevent and/or eradicate pre-operatory metastasis in locally advanced breast cancer.

Improving employee health: evaluation of a worksite lifestyle change program to decrease risk factors for diabetes and cardiovascular disease.

OBJECTIVE: To determine whether an evidence-based, behavioral lifestyle intervention program delivered at a worksite setting is effective in improving type 2 diabetes and cardiovascular disease risk factors. METHODS: A randomized 6-month delayed control design was utilized, with two thirds of the participants assigned to begin intervention immediately, and one third beginning 6 months later. The year-long program (weekly for 3 months transitioning to monthly) focused on weight loss and increasing physical activity. RESULTS: The immediate intervention group had greater mean weight loss (-10.4 lb, 5.1%, vs -2.3 lb, 1%; P = 0.0001) than the delayed control group at 6 months and relatively greater improvements in activity, HbA1c, and other risk factors. The delayed group experienced similar improvements after completing the intervention program. CONCLUSIONS: A worksite behavioral lifestyle intervention is feasible and effective in significantly improving risk factors for type 2 diabetes and cardiovascular disease.

Synthesis, structural characterization and cytotoxic activity of ternary copper(II)-dipeptide-phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer.

In the search for new compounds with antitumor activity, coordination complexes with different metals are being studied by our group. This work presents the synthesis and characterization of six copper complexes with general stoichiometry [Cu(L-dipeptide)(phen)]·nH2O (were phen=1,10-phenanthroline) and their cytotoxic activities against tumor cell lines. To characterize these systems, analytical and spectroscopic studies were performed in solid state (by UV-visible, IR, X-ray diffraction) including the crystal structure of four new complexes (of the six complexes studied): [Cu(Ala-Phe)(phen)]·4H2O, [Cu(Phe-Ala)(phen)]·4H2O, [Cu(Phe-Val)(phen)]·4.5H2O and [Cu(Phe-Phe)(phen)]·3H2O. In all of them, the copper ion is situated in a distorted squared pyramidal environment. The phen ligand is perpendicular to the dipeptide, therefore exposed and potentially available for interaction with biological molecules. In addition, for all the studied complexes, structural information in solution using EPR and UV-visible spectroscopies were obtained, showing that the coordination observed in solid state is maintained. The lipophilicity, DNA binding and albumin interaction were also studied. Biological experiments showed that all the complexes induce cell death in the cell lines: HeLa (human cervical adenocarcinoma), MCF-7 (human metastatic breast adenocarcinoma) and A549 (human lung epithelial carcinoma). Among the six complexes, [Cu(Ala-Phe)(phen)] presents the lowest IC50 values. Taken together all these data we hypothesize that [Cu(Ala-Phe)(phen)] may be a good candidate for further studies in vivo.

Salmonella as live trojan horse for vaccine development and cancer gene therapy.

The design of efficient vectors for vaccine development and cancer gene therapy is an area of intensive research. Bacteria-based vectors are being investigated as optimal vehicles for antigen and therapeutic gene delivery to immune and tumour cells. Attenuated Salmonella strains have shown great potential as live vectors with broad applications in human and veterinary medicine. An impressively high, and still growing, number of reports published over the last two decades have demonstrated the effectiveness in animal models of Salmonella-based therapies for the prevention and treatment of infectious and non-infectious diseases, as well as cancer. Further, the recent dramatic expansion in knowledge of genetics, biology and pathogenesis of the bacteria allows more rational design of Salmonella constructs tailored for specific applications. However, only few clinical trials have been conducted so far, and although they have conclusively demonstrated the safety of this system, the results on immunogenicity are less than optimal. Thus, more research particularly in target species is required to bring this system closer to human and veterinary use. In this review we first describe some particularities of the bacteria and its relationship with the host that could be on the basis of its success as vector, and then summarize the different strategies used so far to develop Salmonella-based vaccines for infectious diseases as well as for non-traditional indications such as prion and Alzheimer disease vaccination. Finally, we review the many different approaches that employ Salmonella for the design of new therapies for cancer.

Migrants travelling to their country of origin: a bridge population for HIV transmission?

BACKGROUND: By having unprotected heterosexual contact in both The Netherlands and their homeland, migrants who travel to their homeland might form a bridge population for HIV and sexually transmitted infection (STI) transmission. We studied the determinants for such a population in two large migrant communities in The Netherlands. METHODS: From 2003 to 2005, 1938 people of Surinamese and Antillean origin were recruited at social venues in two large cities, interviewed and their saliva samples tested for HIV antibodies. We used multivariate multinomial logistic regression to explore characteristics of groups with four risk levels (no, low, moderate and high) for cross-border transmission. RESULTS: 1159/1938 (60%) participants had travelled from The Netherlands to their homeland in the previous 5 years and 1092 (94%) of them reported partnerships and condom use in both countries. Of these 9.2% reported having unprotected sex with partners in both countries. People in this high-risk or bridge population group were more likely to be male, frequent travellers and older compared with people who had no sex or had sexual contact solely in one country in the past 5 years. CONCLUSIONS: Older male travellers of Surinamese and Antillean origin are at high risk for cross-border heterosexual transmission of HIV/STIs. They should be targeted by prevention programmes, which are focused on sexual health education and HIV/STI testing, to raise their risk awareness and prevent transmission.

[Diagnosis of early gastric marginal zone lymphoma (MALT lymphoma) in endoscopic biopsies. Report of a case that demonstrates the utility of immunohistochemistry and the molecular analysis.]. / Diagnóstico del linfoma de la zona marginal (linfoma MALT) gástrico temprano, en biopsiasendoscópicas. Informe de un caso que ilustrala utilidad de la inmunohistoquímica y el análisis molecular.

MALT lymphomas are a subtype of low grade lymphomas that represent 7-8% of all B-cell lymphomas originated in extranodal sites. Nearly 50% of the cases present as primary gastric lymphomas.They arise from the acquired MALT developed during the course of H. pylori chronic infection. Microscopically,the presence of lymphoid follicles with follicular colonization, marginal zone ("centrocytoid")cells and lymphoepithelial lesions is characteristic.Histopathological diagnosis may result difficult in superficial endoscopic biopsies showing a typical lymphoid infiltrates. Using Wotherspoon criteria along with molecular analyses is useful in borderline lesions. We present the case of a 62 years old female with chronic gastritis. A small endoscopic biopsy was performed and the presence of a heterogeneous lymphoid infiltrate in the lamina propia was observed. Immuno histochemical profile showed focal co expression of CD20 andCD43 and kappa light chain restriction. The diagnosis of an atypical lymphoid infiltrate highly suspicious of MALT lymphoma was established. PCR molecular analysis corroborated the monoclonal pattern of the lymphoid cells and the diagnosis of lymphoma. Immunohistochemical and molecular analyses in cases of lymphoid infiltrates suspicious of malignancy (Wotherspoon 3 and 4) will aid in the adequate diagnosis between chronic gastritis and MALT lymphoma, which is crucial for prognosis,treatment and patient's outcome.Key words: Chronic reactive gastritis, marginal zone lymphoma, MALT lymphoma, gastriclym.

Sexual risk behaviour among Surinamese and Antillean migrants travelling to their countries of origin.

OBJECTIVES: To examine travel related sexual risk behaviour among migrants living in Amsterdam. METHODS: People originating from Surinam (n = 798) and the Netherlands Antilles (n = 227) were recruited in order to study the heterosexual spread of HIV within ethnic groups. Log binomial regression was used to study determinants for homeland travel over the past 5 years; logistic regression was used to study determinants of unprotected sex on these visits. RESULTS: Of the migrants, 38% of men and 42% of women visited their homeland. Visits were most likely among men who had lived > or =7 years in the Netherlands, were employed, had a high educational level and were/had been married. For women, visiting was associated with older age and living in the Netherlands for > or =8 years. Of migrants visiting their homeland, 47% of men and 11% of women acquired a local sexual partner. For male travellers, Surinamese origin (adjusted OR 10.66; 95% CI 1.72 to 104.48) and a history of > or =1 sexually transmitted infection (STI) (adjusted OR 12.51; 95% CI 3.75 to 46.95) were associated with having unprotected sex with local partners. For women, having >1 partner in the past 5 years (OR 13.57; 95% CI 2.57 to 250.28) was associated with unprotected sex with local partners. CONCLUSION: Migrants are at substantial risk for HIV and STIs while visiting their homeland. It is important to reach migrants, who are likely to engage in unprotected sex during visits, for pretravel health education. Additional research on risk behaviour in the homeland and the Netherlands is needed to identify migrants with high risk behaviour.

Maternal smoking and the risk of early weaning: a meta-analysis.

OBJECTIVES: This study reviewed evidence on the effect of maternal smoking on early weaning. METHODS: The following databases and journals were searched: Medline, Scientific Citation Index, Pediatrics, Journal of Pediatrics, New England Journal of Medicine, and Lancet. Analysis was restricted to studies in which infants who had never been breastfed were excluded or the prevalence of breastfeeding initiation was more than 90%. RESULTS: In smoking vs nonsmoking mothers, the random effects odds ratio for weaning before 3 months was 1.93 (95% confidence interval [CI] = 1.55, 2.40). An adjusted odds ratio of 1.50 (95% CI = 1.34, 1.68) was shown in studies that had lost-to-follow-up rates below 15% and included adequate adjustment for confounding. CONCLUSIONS: Maternal smoking increases the risk of early weaning.

Urine culture from bag specimens in young children: are the risks too high?

OBJECTIVE: To compare the risks of contaminated culture results and consequent adverse clinical outcomes in urine specimens obtained by "clean-voided" bag method versus catheterization. STUDY DESIGN: Hospital-based cohort study of all children

First reported outbreak of abdominal angiostrongyliasis.

Human abdominal angiostrongyliasis is a potentially fatal disease caused by Angiostrongylus costaricensis, a nematode found in the Americas. During the period of December 1994 through August 1995, an outbreak of this disease occurred in Guatemala. We identified 22 cases of abdominal angiostrongyliasis and conducted a matched case-control study to identify risk factors for illness. The median age of the 18 cases enrolled in the study was 37 years (range, 9-68 years), and 11 (61.1%) were male. Consumption of the following six raw food items was associated with angiostrongyliasis: mint (odds ratio [OR], 6.9; 95% confidence interval [CI], 1.5-66.0), shrimp (OR, infinite; 95% CI, 1.4 to infinite), and four kinds of ceviche that reportedly contained raw mint (OR for consumption of mint or ceviche that contained mint, 7.0; 95% CI, 1.0-315). We conclude that raw mint was the likely vehicle of infection for this outbreak. To our knowledge, this is the first reported outbreak of abdominal angiostrongyliasis and the first time that a specific food item has been epidemiologically linked to the disease.

Molecular epidemiology of autoimmune thyroid disease.

This paper presents preliminary data regarding the prevalence and risk factors for autoimmune thyroid disease in IDDM probands ascertained from the Children's Hospital of Pittsburgh IDDM Registry for 1950-1965 (n = 669). Living IDDM probands who participated in the 1990 follow-up survey (n = 380) were recruited for the Familial Autoimmune and Diabetes Study. Siblings and parents were also invited to participate. To date, 255 IDDM probands and 597 parents and siblings have been evaluated. The diagnosis of autoimmune thyroid disease was based on a clinical evaluation, medical history, and laboratory determinations. Graves disease was rare in this cohort (n = 5). However, Hashimoto's thyroiditis was common among women. Prevalence rates ranged from 54% for IDDM women age < 40 years to 75% for those > 50 years. Corresponding age-specific estimates for female relatives were 22% and 44%, respectively. Approximately one-half of the Hashimoto's individuals were euthyroid; they were more likely to have other autoantibodies and a positive family history than those who were hypothyroid or had no thyroid disease. Genetic analyses revealed a 2-fold increase in DQA1*0501-DQB1*0201 among the Hashimoto's compared to the non-Hashimoto's haplotypes. These findings suggested that Hashimoto's thyroiditis was common in IDDM families, which may be due, in part, to common disease susceptibility genes.