Mesenchymal stromal cells derived from cervical cancer tumors induce TGF-ß1 expression and IL-10 expression and secretion in the cervical cancer cells, resulting in protection from cytotoxic T cell activity.

Cervical cancer (CeCa) tumors are characterized by increased expression of TGF-ß1 and IL-10, which are correlated with downregulated expression of major histocompatibility complex class I antigens (HLA-I) on cancer cells and a reduced immune response mediated by cytotoxic T lymphocytes (CTLs). Mesenchymal stromal cells (MSCs) are important components in the tumor microenvironment that have been suggested to contribute to cancer progression through the induction of TGF-ß1 and IL-10. In this study, we provided evidence that MSCs derived from cervical tumors (CeCa-MSCs) cocultured with CeCa cells induced significant expression of TGF-ß1 and secretion of IL-10 by CeCa cells compared to MSCs derived from the normal cervix (NCx-MSCs) and normal bone marrow (BM-MSCs; gold standard). This increase in expression was associated with a significant downregulation of HLA-I molecules and protection of the cells against specific CTL lysis. Interestingly, the addition of the neutralizing antibody anti-TGF-ß to the CeCa/CeCa-MSCs coculture strongly inhibited the expression and production of IL-10 by CeCa cells. Anti-TGF-ß as well as anti-IL-10 also abolished HLA-I downregulation, and reversed the inhibition of CTL cytotoxicity. These results provide evidence that TGF-ß1 and IL-10 could play an important role in the downregulation of HLA-I molecules on CeCa cells induced by tumor MSCs. Our findings suggest a novel mechanism through which MSCs may protect tumor cells from immune recognition by specific CTLs.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

Effect of glycophosphopeptide on the lymphocytes and IgA of Olympic platform divers.

AIM: The aim of this paper was to evaluate the effect of a treatment with glycophosphopeptide on Olympic high platform divers during training and competition by measuring lymphocytes and cortisol in peripheral blood, and secretory immunoglobin A in saliva (sIgA). METHODS: Two groups of 8 divers were given a 14-day treatment of capsules (Gp or placebo) three times per day. Measurements of the peripheral blood lymphocytes (TCD3+, TCD4+ and T CD8+), plasma cortisol and IgA levels in saliva were made on day 0, 21 and 150. RESULTS: There was no significant difference found between the Gp- and placebo-treated groups regarding the increase in IgA between basal and first, or first and second measurements. The fact that there was a significant increase in S-IgA (9.89 ± 0.44 to 10.59±0.55, P=0.001) and B CD19+ (345.13±108.24 to 484.75±120.54, P=0.025) in the Gp- and not in the placebo-treated group between the basal and first measurement was due to the variation among the athletes of the latter group, and not the increase itself, indicating that Gp acted as an immunomodulator. It was apparently the exercise and not the Gp treatment that caused the increase in S-IgA and B CD19+ at the first and second measurements. CONCLUSION: The current study reports that with athletes who practiced moderately intense exercise, which stimulated the immune response, a Gp treatment of two weeks seems to have acted only as an immunomodulator that reduced the variation in the increased levels of IgA and B CD19+.

In search of effective bioassessment of urban stormwater pond sediments: enhancing the 'sediment quality triad' approach with oligochaete metrics.

Stormwater ponds have been widely used to control increased volumes and rates of surface runoff resulting from urbanization. As receiving waters, they are under the influence of intermittent pollution from urban wet-weather discharges. Meanwhile they offer new aquatic habitats balancing the transformation of initial ecosystems and their associated biodiversity. Bioassessment of stormwater facilities is therefore crucial to insure the preservation and rehabilitation of biodiversity in urban areas. Nonetheless, the application of traditional bioassessment methodologies such as the sediment quality triad (SQT), based on the comparisons with reference sites, is challenged by the artificial and atypical features of urban stormwater ponds. Our concern in finding a more specific and effective bioassessment methodology led us to consider associating the Oligochaete Index Methodology (OIM) with the SQT. This study shows that although some adjustments were needed, the OIM brought new and complementary information to the SQT assessment on the effects of contaminants and on the biological quality status of the sediment in a test urban stormwater pond.

Dalbavancin for treating prosthetic joint infections caused by Gram-positive bacteria: A proposal for a low dose strategy. A retrospective cohort study.

OBJECTIVE: Gram-positive bacteria are the leading cause of prosthetic joint infection (PJI). Dalbavancin is a lipoglycopeptide with remarkable pharmacokinetic properties and high bactericidal activity against most Gram-positive bacteria. Although clear evidence regarding its effectiveness in bone and joint infections lacks, recent studies suggest a promising role of dalbavancin in PJI. METHODS: From June 1st 2016 to May 1st 2018, all patients diagnosed of PJI and treated with DAL alone or in combination with other drugs were retrospectively evaluated. Dalbavancin susceptibility of every isolate was studied following CLSI criteria. The primary objective was to assess the clinical efficacy and tolerability of the drug in patients with PJI. A cost-analysis was performed following the DALBUSE study methodology. RESULTS: Sixteen patients were treated with dalbavancin, eight with total hip arthroplasty infection (THAi) and eight with total knee arthroplasty infection (TKAi). Staphylococcus spp. and Enterococcus spp. were the microorganisms involved. No major side effects were detected. Infection resolved in 12 patients. In 2 patients the treatment failed, and another patient died due to unrelated causes. One patient is currently being treated for hematogenous-spread knee infection secondary to prosthetic aortic arch endocarditis. After discontinuation of dalbavancin, and excluding patients who died or with clinical failure, the median follow up of the cohort was 503 days (interquartile range IQR, 434.5 to 567 days). We calculate that US$ 264,769 were saved. CONCLUSIONS: This study suggests that dalbavancin treatment for PJI caused by Gram-positive bacteria is a safe and effective option that reduces hospital stay and costs. Future reports are needed to confirm these findings.

Bioassessment of wet-weather pollution impacts on fine sediments in urban waters by benthic indices and the sediment quality triad.

Benthic invertebrate assessments can be used to gauge the impact of urban wet-weather flows in receiving waters. Experiences from Cemagref in France have shown that standardized benthic indices (e.g. Oligochaete Index of Sediment Bioindication - IOBS) can be used to reliably determine the ecological status of urban streams and can be incorporated into the new European Water Framework Directive. The Canadian studies on streams and stormwater ponds using chemical analyses, benthic toxicity testing and benthic invertebrate community structure (i.e. the sediment quality triad) comparisons have shown that toxicity was more likely to occur in ponds at sites with higher concentrations of heavy metals and heavier polycyclic aromatic hydrocarbons, and at greater water depths, where fine sediments from urban runoff accumulated. A more comprehensive evaluation of wet-weather flow impacts could be obtained by combining approaches from both countries.

[Accuracy of ultrasound estimated fetal weight at term]. / Performance de l'échographie dans l'estimation du poids fœtal à terme.

OBJECTIVES: Our aim was to evaluate the accuracy of estimated fetal weight (EFW) by ultrasound at due date and the factors that could affect it. METHODS: We performed a retrospective study of 233 patients in 2014. An ultrasound was performed at due date consultation around 41 weeks of amenorrhea by midwives sonographer. EFW was calculated using the Hadlock's formula with 3 parameters (biparietal diameter, abdominal circumference and femur length) and then adjusted including the growth from the due date consultation to the day of delivery (25g/day) and finally compared to birth weight (BW). RESULTS: The mean absolute weight difference between EFW adjusted and BW was 256g [0; 910]. The mean absolute percentage error was 7.2 % [0; 24.5] and the proportion of the EFW adjusted within 10 % of BW was 69.1 %. There was a strong correlation between EFW adjusted and BW (R=0.79). Obesity in early pregnancy or childbirth, excessive weight gain, the presence of oligoanamnios and fetal macrosomia had no influence on the estimated fetal weight. Indeed, the mean absolute percentage error of child who were macrosome and those were not, was similars (7.9 % vs 7.1 %, P=0.407). CONCLUSIONS: EFW by ultrasound at due date is performant. However, the adjustment by the effect growth does not improve accuracy. Fetal macrosomia do not decrease the accuracy of ultrasound to estimate the fetal weight at term.

CD4+ CD25+ lymphocyte and dendritic cell mobilization with intermediate doses of recombinant human granulocyte colony-stimulating factor in healthy donors.

We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.

Frey syndrome: factors influencing the time to event.

Frey syndrome is a common complication after parotidectomy. The time from surgery to disease onset may be quite long; therefore, a time-to-event analysis was performed for the occurrence of this syndrome post-parotidectomy. Three hundred and thirty-four patients who underwent a parotidectomy between January 2002 and November 2012 were identified (retrospective study). Of these patients, 102 developed Frey syndrome post-surgery and 232 did not. The time-to-onset analysis enabled us to estimate the risk ratio associated with different types of parotid gland tumours, various parotidectomy procedures, and repeat parotidectomy, which is useful for predicting preoperative and surgical risk. The risk of developing Frey syndrome was lower in patients with malignant tumours than in those with benign tumours (risk ratio 0.351, 95% confidence interval (CI) 0.155-0.594). Risk ratios for lumpectomy PA (pre-auricular area), superficial parotidectomy, and total parotidectomy with respect to lumpectomy T (tail) were 4.378 (95% CI 1.168-16.410), 8.040 (95% CI 3.286-19.670), and 8.174 (95% CI 3.076-21.723), respectively. Repeat parotidectomy also increased the risk of developing Frey syndrome (risk ratio 3.214, 95% CI 1.547-6.678). No effect of the use of a superficial muscular aponeurotic system (SMAS) flap on the risk of developing Frey syndrome was detected (P=0.888).

Per-operative hemodynamic instability in normotensive patients with incidentally discovered pheochromocytomas.

CONTEXT: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented. OBJECTIVE: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs). DESIGN: Retrospective cohort treated in a single center. PATIENTS AND METHODS: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording. RESULTS: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03). CONCLUSIONS: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia.

An annual survey of bacterial production, respiration and ectoenzyme activity in coastal NW Mediterranean waters: temperature and resource controls.

We simultaneously measured bacterial production (BP), bacterial respiration (BR), alkaline phosphatase activity (phos) and ectoaminopeptidase activity (prot) in relation to biogeochemical parameters, nutritive resources and in situ temperature over a 1-year survey at the long-term observatory the SOLEMIO station (Marseille bay, NW Mediterranean Sea). Despite its proximity to the coast, oligotrophic conditions prevailed at this station (yearly mean of Chl a = 0.43 µg dm(-3), NO3 = 0.55 µmol dm(-3) and PO4 = 0.04 µmol dm(-3)). Episodic meteorological events (dominant winds, inputs from the Rhone River) induced rapid oscillations (within 15 days) in temperature and sometimes salinity that resulted in rapid changes in phytoplankton succession and a high variability in C/P ratios within the particulate and dissolved organic matter. Throughout the year, BP ranged from 0.01 to 0.82 µg C dm-(3) h-(1) and bacterial growth efficiency varied from 1 to 39%, with higher values in summer. Enrichment experiments showed that BP was limited most of the year by phosphorus availability (except in winter). A significant positive correlation was found between in situ temperature, BP, BR and phos. Finally, we found that temperature and phosphate availability were the main factors driving heterotrophic bacterial activity and thus play a fundamental role in carbon fluxes within the marine ecosystem.

[Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the upper urinary tract]. / Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation", "chemotherapy", and adjuvant.

Validation of biomarkers for impact evaluation of aqueous industrial waste in mesocosms.

The use of exposure biomarkers in measuring the impact of aqueous waste holds promise because such tools have short response times, are flexible in use and may give an indication about the type of pollution. However, their ecological significance has not yet been demonstrated. It is necessary to validate these responses under controlled conditions before using such biomarkers for biomonitoring. The TotalFinaElf company has developed a pilot scheme incorporating such controlled conditions. This pilot is a dynamic open mesocosm (16 channels 40 m in length supplied with river water). The research programme currently carried out in the "Pilot Rivers" aims at validating biochemical parameters (components of phases I and II (de)toxication metabolism and propionylcholinesterase activity), measured in a fresh water bivalve Corbicula fluminea as a biomarker of water quality. The comparison between biomarker responses and community ones (reference) gives information about the precocity and sensitivity of these biomarker responses. Pure substances (trichloroethylene (TCE), cadmium (CD) and anthracenic oil (AO)) have been injected during one month. Biomarker responses are as sensitive as the most sensitive community response in the presence of CD and AO. With TCE, community responses are more sensitive. Precocity of biomarker response is observed only in the presence of CD.

[Favorable outcome of a subdural hematoma diagnosed in utero]. / Evolution favorable d'un hématome sous-dural diagnostiqué in utero.

UNLABELLED: The subdural hematoma detected in utero is unusual but probably under-diagnosed and has a bad prognostic. CASE REPORT: A newborn had a subdural hematoma detected with a prenatal ultrasonography at 31 weeks' gestation, probably in keeping with the regular treatment of AAS. Diagnosis was possible through antenatal MRI at 34 weeks' gestation. The mother chose to follow her pregnancy. The operation at day 3 had no complications and neurological progress at 12 months was very good. CONCLUSION: A subdural hematoma detected in utero may have a good prognostic. Prenatal MRI is useful for the check-up. However, medical and ethical problems remain in these cases.

[Results of surgery of vitreomacular traction syndromes]. / Résultats de la chirurgie des syndromes de traction vitréo-maculaire.

PURPOSE: The vitreomacular traction syndrome is a rare entity in which partial posterior vitreous detachment is combined with persistent macular adherence, thus causing macular traction. In most cases, an epimacular membrane is associated with this vitreomacular traction. We evaluate here the results of vitreous surgery for this syndrome. METHODS: We reviewed 18 consecutive eyes that had undergone vitrectomy and posterior epiretinal membrane stripping, to define the visual results and complications of surgery for the vitreomacular traction syndrome. Minimum follow-up was 3 months. RESULTS: Patients' average age was 63.5 years. All had evidence of cystic macular changes on biomicroscopic examination. Sixteen patients had an epiretinal membrane, and two, a full-thickness macular hole. Cystoid macular edema was present in 7 eyes on fluorescein angiography. The release of vitreomacular traction improved vision in 72% of eyes, with six patients obtaining 20/40 visual acuity or better. Complications of surgery included progression of nuclear sclerosis, and epiretinal membrane formation. CONCLUSION: Vitrectomy for vitreomacular traction syndrome may improve visual acuity, but the visual prognosis remains poor.

[Observational study on the efficacy of the application of two classical regimens of triple antiretroviral therapy]. / Estudio de campo sobre la eficacia de la aplicación de dos modalidades clásicas de triple terapia antirretroviral.

BACKGROUND: To compare the temporal evolution of viral load and CD4 parameters in two cohorts of HIV infected patients enrolled in classical triple antiretroviral regimens. METHODS: Retrospective, observational, descriptive study of the proportions of patients reaching undetectable levels of viral load (VL) as well as the time necessary to get it. The two cohorts were as follows: 91 HIV patients on triple therapy with zidovudine plus lamivudine and indinavir (cohort A) versus 80 HIV patients with Stavudine plus Didanosine and Indinavir (cohort B). RESULTS: The evolution of the patients in terms of percentages who reach undetectable VL was similar in the two therapeutic cohorts (75.8%for cohort A vs 73.8% for cohort B) along the duration of the study (four years). However, the mean time period needed to reach undetectable VL was different, 209 days (IC 95% 175-243 days) for patients in zidovudine plus lamivudine and indinavir and 330 days (IC 95% 263-396 days) for stavudine plus didanosine and indinavir regimen. The immunological status observed in the patients when reaching his first undetectable VL was significantly different. The proportion of patients with CD4 cells counts >200/mm3 in cohort A was 83.1% while for patients from cohort B was 65.4% (p=0.032). CONCLUSIONS: This observational study from clinical settings seems demonstrate similar efficacy to reach undetectable VL with both classical triple antiretroviral therapies evaluated but a shorter delay of time to reach that virological situation for zidovudine plus lamivudine and indinavir regimen is reported.

Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in humans.

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still unknown. Our goal was to determine whether PRL plays a role in T(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.