Does urbanisation have an impact on the trophic ecology of the Algerian hedgehog Atelerixalgirus in northern Algeria?

The Algerian hedgehog, which is an endemic Mediterranean species, is a nocturnal and terrestrial insectivorous mammal. Atelerixalgirus' populations are widespread in various habitats comprising human agglomeration, such as rural, suburban or natural ecosystems. However, the impact of the habitat's characteristics on its diet remains unknown in Algeria. To contribute to a better understanding of this question, we have analysed 158 faeces samples of the Algerian hedgehog in three different areas: urban, suburban and natural area. The findings show that the Algerian hedgehog is an opportunistic species. It feeds on several classes of Arthropoda, but the harvester ant Messorbarbarus dominates largely its menu with AR = 74.81% in the diverse habitats. Furthermore, the HAC and FCA analyses confirm the positive impact of the level of urbanisation and the anthropogenic activity on the Algerian hedgehog prey richness in the north of Algeria (79 prey species and 5574 individuals ingested in the urban area, compared to 64 prey species and 3188 individuals ingested in the natural zone).

Molecular identification and evaluation of Coxiella-like endosymbionts genetic diversity carried by cattle ticks in Algeria.

Coxiella-like bacteria are a large group of yet-to-isolate and characterize bacteria phylogenetically close to the agent of Q fever, Coxiella burnetii, and often associated with ixodid ticks worldwide. This study was designed to assess the presence of Coxiella-like endosymbionts (CLE) in ticks and to describe their genetic diversity in different tick species infesting cattle in Algeria. A total of 765 ticks were collected from three locations. The screening of 20 % of sampled ticks (147/765) exhibited the presence of Coxiella-like in 51.7 % (76/147). The sequencing of partial 16S rRNA and the GroEl genes showed an identity higher than 98 % with different Coxiella-like endosymbionts. The phylogenetic analysis based on the 16S rRNA gene showed the positions of identified Coxiella bacteria. Eleven of the 13 sequences from Rhipicephalus, Dermacentor and Hyalomma ticks were grouped in a distinct clade, the other two each represent an independent clade. This study reported that CLE are prevalent in cattle ticks. Most of the identified Coxiella-like bacteria, from different species of ticks found on cattle, were identical. This may mean that, unlike the currently accepted paradigm, Coxiella-like bacteria are not only tick host-associated, but rather can be transmitted from one tick species to another via the vertebrate host.

A Comprehensive Structure-Function Study of Neurogenin3 Disease-Causing Alleles during Human Pancreas and Intestinal Organoid Development.

Neurogenin3 (NEUROG3) is required for endocrine lineage formation of the pancreas and intestine. Patients with NEUROG3 mutations are born with congenital malabsorptive diarrhea due to complete loss of enteroendocrine cells, whereas endocrine pancreas development varies in an allele-specific manner. These findings suggest a context-dependent requirement for NEUROG3 in pancreas versus intestine. We utilized human tissue differentiated from NEUROG3-/- pluripotent stem cells for functional analyses. Most disease-associated alleles had hypomorphic or null phenotype in both tissues, whereas the S171fsX68 mutation had reduced activity in the pancreas but largely null in the intestine. Biochemical studies revealed NEUROG3 variants have distinct molecular defects with altered protein stability, DNA binding, and gene transcription. Moreover, NEUROG3 was highly unstable in the intestinal epithelium, explaining the enhanced sensitivity of intestinal defects relative to the pancreas. These studies emphasize that studies of human mutations in the endogenous tissue context may be required to assess structure-function relationships.

Increased Level of Factor VIII and Physiological Inhibitors of Coagulation in Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolysis, oxidative stress, and vaso-occlusive crises. Thromboembolism also remains a serious complication and probably underestimated in the SCD. Our objective was to seek the existence of hemostasis abnormalities that predispose to thrombosis such as elevation of FVIII and Physiological inhibitors of coagulation deficiency. We studied 81 patients with SCD, including 32 homozygous S/S, 20 double heterozygous S/ß thalassemia and 29 heterozygous S/A. Controls AA were in number 60. For each patient and control we assayed the physiological coagulation inhibitors (Protein C, Protein S and Antithrombin) and the clotting FVIII. We found a significant increase in FVIII in all phenotypes of SCD compared to controls. Also, a significant decrease in levels of protein C and S was observed in patients with sickle cell homozygous or double heterozygous S ß Thalassemia compared to controls. As against, for antithrombin no difference was observed between patients and controls. These hemostasis abnormalities therefore reflect the existence of a pro thrombotic state in sickle cell disease that can explain the increase of incidence of thrombosis in this pathology. Factor VIII clotting consistently high in SCD may well be a prime therapeutic target in the treatment of thrombotic manifestations of this disease.

Whole body 18F-FDG PET predicts progression free and overall survival in squamous cell carcinoma of the esophagus: results of a prospective trial.

BACKGROUND AND OBJECTIVES: 18F-FDG PET yields physiologic information that allows for identifying cancer based on altered tissue metabolism. The aim of this study was to prospectively validate the predictive value of positron emission tomography (PET) in squamous cell carcinoma (SCC) of the esophagus treated by pre-operative chemotherapy followed by esophagectomy. DESIGN AND SETTING: Prospective efficacy and toxicity study of patients enrolled between January 1999 and September 2003. PATIENTS AND METHODS: Twenty-one patients with SCC of the esophagus who were potentially resectable underwent 18F-FDG PET imaging before the first cycle of neoadjuvant chemotherapy and at least 14 days after the third cycle. A patient was classified as a metabolic responder when the metabolic activity of the primary tumor as measured by the maximum standardized uptake values had decreased by 50% or more at the time of the second 18F-FDG PET. RESULTS: The median age of the study cohort was 60 years with a range of 39-70 years; 12 patients were males and 9 were females. 18F-FDG PET had increased activity in the primary tumor in all patients. Metabolic response occurred in 14/21 patients (66%), while 7/21 (33%) patients did not show a metabolic response. Metabolic responders had a high clinical response rate (92%), a median progression free survival (PFS) of 16.4 months and a median overall survival (OS) of 35.3 months. In contrast, prognosis was poor for metabolic non-responders with a clinical response rate of 42% (P=.025), a median PFS of 7.13 months (P=.032) and median OS of 12 months (P=.038). CONCLUSION: Our results demonstrate that changes in tumor metabolic activity after neoadjuvant chemotherapy predicts PFS and OS in esophageal SCC patients.

Improved survival with combined chemo-radiotherapy in primary central nervous system lymphoma.

BACKGROUND: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). METHODS: All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demographic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were excluded (4 had WBI<40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose>40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI. RESULT: Of 52 patients analyzed for outcome, 36 had WBI (dose>40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI. Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. x22%, p=.029). Median follow up was 12.83±6.4 months. The hazard ratio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60 years), ECOG PS (0-2 vs. 3-4), extent of surgery (biopsy vs. debulking), solitary vs multifocal tumor and dose of radiation therapy (<50 Gy vs. >50 Gy) failed to identify any prognostic factor. CONCLUSION: This retrospective comparison supports phase II trial results that indicate that high-dose methotrexate followed by WBI in PCNSL improves outcome.

Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer.

The objective of this study is to evaluate the efficacy and safety profile of the doxorubicin followed by cisplatin/docetaxel as primary chemotherapy for patients with locally advanced breast cancer (LABC). For this evaluation, 59 patients with LABC (T2-T4, N0-N2, M0) received three cycles of doxorubicin, followed by three cycles of cisplatin/docetaxel and followed by definitive surgery and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast and axilla. Fifty-nine patients were evaluable for analysis: median age: 41 years, premenopausal: 68%, median tumor size: 6.0 cm (4-10), Stage IIB: 32% and IIIA/IIIB: 68%, both ER/PR positive: 53%, Her2/neu (3+) by IHC staining: 29%. Clinical complete response was seen in 44%, and clinical partial response was seen in 56%. Breast conserving surgery was performed in 44%, and MRM in 56%. pCR in the breast was 30.5%, in axilla was 37%, and pCR in both breast and axilla was 24%. Overall at follow-up of 60 months, the disease-free (DFS) and overall survival (OS) were 70 and 82%, respectively. The DFS and OS of patients who achieved complete pathologic response in breast and axilla were 78 and 100%, respectively, while 14 patients relapsed of which 46% were Her2 positive. Sequential combination of doxorubicin followed by docetaxel/cisplatin is a safe, feasible, and active combination, which offers the possibility of conservative surgery and is associated with high clinical and pathologic response rates, with promising and encouraging survival outcomes.

Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors.

Metaplastic carcinoma of the breast (MCB) is a rare form of cancer containing mixture of epithelial and mesenchymal elements in variable combinations. Few and conflicting clinical data are available in the literature addressing optimal treatment modalities, prognosis and outcome. A retrospective study was conducted to review all patients with MCB diagnosed and treated at King Faisal Specialist Hospital and Research Center between 1994-2004. The aim is to describe patient's clinicopathologic features and to analyze treatment results. Nineteen female patients were studied. The median age was 48 years (range, 14-58). The median tumor size was 9 cm (range, 3-18). Stage distribution was II in 8 patients, III in 9 and IV in 2. Nine cases were identified as purely epithelial and 10 (53%) as mixed epithelial and mesenchymal metaplasia. Hormone receptors were positive in only 2 patients. Modified radical mastectomy performed in 11 patients and 15 underwent axillary node dissection. Adjuvant chemotherapy was given to 9 patients and postoperative radiotherapy to 8. Twelve patients relapsed with median time of relapse of 12 months (range, 2-28). At a median follow-up of 21 months (range, 7-83), the 3-year event free survival (EFS) and overall survival for the patients diagnosed with loco-regional disease were 15% and 48% respectively. Tumor size correlated significantly with EFS. MCB is an aggressive form of breast cancer associated with poor outcome, high incidence of local recurrence and pulmonary metastases. The disease tends to be estrogen/progesterone receptor negative. Tumor size has an important impact on outcome. The best treatment approach is yet to be defined.

VIP (etoposide, ifosfamide, cisplatin) in adult patients with recurrent or refractory Ewing sarcoma family of tumors.

Despite the fact that Ewing sarcoma family of tumors (ET) is chemosensitive, long-term survival is extremely rare for patients with primary refractory or recurrent disease. There is no standard salvage chemotherapy regimen available in this context. In this study the authors reviewed their experience with the combination of etoposide, ifosfamide, and cisplatin in adult patients with recurrent or refractory disease. From February 1997 through December 2001, they evaluated the efficacy of etoposide (75 mg/m2/day for 5 days), ifosfamide (1,200 mg/m2/day for 5 days), and cisplatin (20 mg/m2/day for 5 days) combination chemotherapy (VIP regimen), as second-line salvage therapy in 27 patients with recurrent or refractory ET. All patients were evaluated for response, time to progression, and overall survival. Twenty-one male and 6 female patients with recurrent (n = 14) and refractory (n = 13) disease were treated with the VIP regimen. Median age was 18 years (range, 16-34 years). Twenty-two patients were previously treated with vincristine, Adriamycin, ifosfamide, and actinomycin-D; and 5 patients were treated with cyclophosphamide, Adriamycin, and vincristine. Sites of recurrent or progressive disease included local (n = 3), distant (n = 11), and both local and distant (n = 13). A total of 129 cycles of VIP were given (median, 5 cycles/patient; range, 1-14 cycles/patient). One patient (4%) had a complete response (CR) and 8 patients (30%) had a partial response (PR), for an overall response rate of 34%. The median number of cycles given to patients with CR + PR was 6 (range, 3-14 cycles). Nine patients (33%) had stable disease and 9 (33%) had disease progression. Median time to progression and median overall survival were 6.6 months and 8.1 months respectively for all patients, and 12.8 months and 14.2 months respectively for responders. There were no toxic deaths. Major toxicities included grade IV granulocytopenia in 19 patients and grades III/IV thrombocytopenia in 15 patients. At a median follow-up of 8 months (range, 2-56 months), 24 patients died of disease progression, 2 patients are alive with disease, and 1 patient is alive with no evidence of disease. The authors conclude that the VIP combination is active in patients with recurrent/refractory ET, with acceptable toxicity, and offers good palliation. Cisplatin-based combination chemotherapy merits further investigation, possibly as first-line treatment in this disease.