Epidemiologic confirmation that fruit consumption influences mercury exposure in riparian communities in the Brazilian Amazon

Since deforestation has recently been associated with increased mercury load in the Amazon, the problem of mercury exposure is now much more widespread than initially thought. A previous exploratory study suggested that fruit consumption may reduce mercury exposure. The objectives of the study were to determine the effects of fruit consumption on the relation between fish consumption and bioindicators of mercury (Hg) exposure in Amazonian fish-eating communities. A cross-sectional dietary survey based on a 7-day recall of fish and fruit consumption frequency was conducted within 13 riparian communities from the Tapajós River, Brazilian Amazon. Hair samples were collected from 449 persons, and blood samples were collected from a subset of 225, for total and inorganic mercury determination by atomic absorption spectrometry. On average, participants consumed 6.6 fish meals/week and ate 11 fruits/week. The average blood Hg (BHg) was 57.1 +/- 36.3 microg/L (median: 55.1 microg/L), and the average hair-Hg (HHg) was 16.8 +/- 10.3 microg/g (median: 15.7 microg/g). There was a positive relation between fish consumption and BHg (r = 0.48; P<0.0001), as well as HHg (r =0.34; P<0.0001). Both fish and fruit consumption entered significantly in multivariate models explaining BHg (fish: beta = 5.6, P<0.0001; fruit: beta = -0.5, P = 0.0011; adjusted model R2 = 36.0%) and HHg levels (fish: beta = 1.2, P<0.0001; fruit: beta = -0.2, P = 0.0002; adjusted model R2 = 21.0%). ANCOVA models showed that for the same number of fish meals, persons consuming fruits more frequently had significantly lower blood and HHg concentrations. For low fruit consumers, each fish meal contributed 9.8 microg/L Hg increase in blood compared to only 3.3 microg/L Hg increase for the high fruit consumers. In conclusion, fruit consumption may provide a protective effect for Hg exposure in Amazonian riparians. Prevention strategies that seek to maintain fish consumption while reducing Hg exposure in fish-eating communities should be pursued.     

New insight into the role of ANXA1 in melanoma progression: involvement of stromal expression in dissemination

ANXA1, first described in the context of inflammation, appears to be deregulated in many cancers and increased in melanomas compared with melanocytes. To date, few studies have investigated the role of ANXA1 in melanoma progression. Furthermore, this protein is expressed by various cell types, including immune and endothelial cells. We therefore analyzed the specific roles of ANXA1 using melanoma and stromal cells in two human cell lines (A375-MA2 and SK-MEL-28) in vitro and in Anxa1 null C57Bl6/J mice bearing B16Bl6 tumors. We report decreased proliferation in both ANXA1 siRNA A375-MA2 and SK-MEL-28, but cell-dependent effects of ANXA1 in migration in vitro. However, we also observed a significant decrease of B16Bl6 tumor growth associated with a reduction of Ki-67 positive cells in Anxa1 null mice compared with wild-type mice. Interestingly, we also found a significant reduction of spontaneous metastases, which can be attributed to decreased angiogenesis concomitantly with greater immune cell presence in the Anxa1 null stromal context. This study highlights the pejorative role of ANXA1 in both tumor and stromal cells in melanoma, due to its involvement in proliferation and angiogenesis.     

Lipid homeostasis and inflammatory activation are disturbed in classically activated macrophages with peroxisomal β‐oxidation deficiency

Macrophage activation is characterized by pronounced metabolic adaptation. Classically activated macrophages show decreased rates of mitochondrial fatty acid oxidation and oxidative phosphorylation and acquire a glycolytic state together with their pro‐inflammatory phenotype. In contrast, alternatively activated macrophages require oxidative phosphorylation and mitochondrial fatty acid oxidation for their anti‐inflammatory function. Although it is evident that mitochondrial metabolism is regulated during macrophage polarization and essential for macrophage function, little is known on the regulation and role of peroxisomal β‐oxidation during macrophage activation. In this study, we show that peroxisomal β‐oxidation is strongly decreased in classically activated bone‐marrow‐derived macrophages (BMDM) and mildly induced in alternatively activated BMDM. To examine the role of peroxisomal β‐oxidation in macrophages, we used Mfp2^?/? BMDM lacking the key enzyme of this pathway. Impairment of peroxisomal β‐oxidation in Mfp2^?/? BMDM did not cause lipid accumulation but rather an altered distribution of lipid species with very‐long‐chain fatty acids accumulating in the triglyceride and phospholipid fraction. These lipid alterations in Mfp2^?/? macrophages led to decreased inflammatory activation of Mfp2^?/? BMDM and peritoneal macrophages evidenced by impaired production of several inflammatory cytokines and chemokines, but did not affect anti‐inflammatory polarization. The disturbed inflammatory responses of Mfp2^?/? macrophages did not affect immune cell infiltration, as mice with selective elimination of MFP2 from myeloid cells showed normal monocyte and neutrophil influx upon challenge with zymosan. Together, these data demonstrate that peroxisomal β‐oxidation is involved in fine‐tuning the phenotype of macrophages, probably by influencing the dynamic lipid profile during macrophage polarization.     

Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison with Matched Related,Haplo-Mismatched,and Unrelated Donors

The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematologic malignancies are poor. Sequential strategies have shown promising results in refractory acute myelogenous leukemia (AML), but have not been validated in a haploidentical (Haplo) transplant setting. We have developed a new sequential approach combining chemotherapy with broad antitumor activity (thiotepa 10?mg/kg, etoposide 400?mg/m², and cyclophosphamide 1600?mg/m² from day -15 to day -10), followed after 3 days of rest by a reduced-intensity conditioning regimen (fludarabine 150?mg/m², i.v. busulfan 6.4?mg/kg, and thymoglobulin 5?mg/kg from day -6 to day -2). High-dose post-transplantation cyclophosphamide was added in cases with Haplo donors. Seventy-two patients (median age, 54 years) with a refractory hematologic malignancy (44 with acute myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were included in this retrospective multicenter study. Donors were Haplo (n?=?27), matched related (MRD; n?=?16), and unrelated (UD; n?=?29). With a median follow-up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS) were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and 43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%, respectively, in recipients of UD transplants. Compared with UD, the outcomes were improved in Haplo in terms of the incidences of acute grade II-IV graft-versus-host disease (GVHD) (11.1% versus 41.4%; P?<?.001) and GVHD-free, relapse-free survival (44.4 versus 10.3%; P?=?.022). These results support the safety and efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo donor with post-transplantation immune modulation. Thus, in patients with refractory hematologic malignancies, there seems to be no benefit in searching for a UD when a Haplo donor is readily available.     

The Role of Computed Tomography in the Diagnosis of Necrotizing Soft Tissue Infections

Background

The exact role of IV contrast-enhanced computed tomography (CT) in the diagnosis of necrotizing soft tissue infections (NSTIs) has not yet been established. We aimed to explore the role of CT in patients with clinical suspicion of NSTI and assess its sensitivity and specificity for NSTI.

Methods

The medical records of patients admitted between 2009 and 2016, who received IV contrast-enhanced CT to rule out NSTI, were reviewed. CT was considered positive in case of: (a) gas in soft tissues, (b) multiple fluid collections, (c) absence or heterogeneity of tissue enhancement by the IV contrast, and (d) significant inflammatory changes under the fascia. NSTI was confirmed only by the presence of necrotic tissue during surgical exploration. NSTI was considered absent if surgical exploration failed to identify necrosis, or if the patient was successfully treated non-operatively.

Results

Of the 184 patients, 17 had a positive CT and hence underwent surgical exploration with NSTI being confirmed in 13 of them (76%). Of the 167 patients that had a negative CT, 38 (23%) underwent surgical exploration due to the high clinical suspicion for NSTI and were all found to have non-necrotizing infections; the remaining 129 (77%) were managed non-operatively with successful resolution of symptoms. The sensitivity of CT in identifying NSTI was 100%, the specificity 98%, the positive predictive value 76%, and the negative predictive value 100%.

Conclusions

A negative IV contrast-enhanced CT scan can reliably rule out the need for surgical intervention in patients with initial suspicion of NSTI.

     

State of unmet medical needs in France in 2006: necessity of reinforcing research effort

Leem (French Pharmaceutical Companies) realized an inventory of unmet medical needs in 2006 in France for 12 pathologies. All of them are considered as national public health priorities by the law of August 9th, 2004. Allied to the epidemiological projections, analyses concerned various stages and/or pathology forms, impact of guidelines in clinical practice, therapeutic strategies, marketed therapeutics and pharmacological products in an advanced phase of clinical development. With more than 100 products listed in clinical phase III or pre-registration/marketed for those pathologies, French Pharmaceutical Companies contribute, quasi exclusively, to the development of innovative pharmaceutical products to answer unmet medical needs. This study illustrates the necessity of French Government to support therapeutic innovation led by Pharmaceutical Companies in France.     

Ceratomyxa gouletti n. sp. (Myxosporea: Ceratomyxidae), a parasite of the red scorpionfish Scorpaena scrofa (L.) from Tunisian waters

Parasitology Research - Ceratomyxa gouletti n. sp. is a new parasite described from the gallbladder of the red scorpionfish Scorpaena scrofa (Scorpaeniformes: Scorpaenidae) collected from La...