Kaposi sarcoma in an HIV-negative Tunisian patient: A rare cause of metatarsalgia

AbstractBackgroundKaposi sarcoma (KS) is an angioproliferative neoplasm that is commonly associated with human herpes virus-8 (HHV-8) and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). KS with osseous involvement is a rare occurrence, and is far more common in acquired immunodeficiency syndrome (AIDS)-related KS.Case presentationWe present a 32-year-old Tunisian man, HIV negative, who presented with a 4-year history of atraumatic mechanical metatarsalgia that progressively worsened with a limping gait. Physical examination revealed marked symmetrical forefoot lymphedema and a painful restricted left knee joint movement. Physical examination showed purple-blue plaques and nodules on the feet and ankles. Serologic tests for HIV and syphilis were negative. Plain radiography of the feet revealed numerous small lytic lesions. There were also scattered lytic lesions in the metaphysis of the proximal tibia and fibula. Osteolysis was predominantly left. Magnetic resonance imaging of the feet showed abnormal bone marrow signal of metatarsals and phalanges. Skin lesion biopsy yielded the diagnosis of Kaposi sarcoma. The disease was managed with chemotherapy including vinblastine.ConclusionIn a patient presenting with metatarsalgia without a commonly detected cause, it is mandatory to search for other lesions that may point to a rare diagnosis as KS which is famous for involvement of the metatarsal bone

Prevalence of hemoglobin variants in a diabetic population at high risk of hemoglobinopathies and optimization of HbA1c monitoring by incorporating HPLC in the laboratory workup

Background: In Tunisia, diabetes mellitus and hemoglobinopathies are major public health problems. Glycated hemoglobin (HbA1c) is  recommended for long-term monitoring of diabetes mellitus, but the presence of hemoglobin variants may interfere with HbA1c measurement. The aim was to determine the prevalence of hemoglobin variants in Tunisian diabetics and optimize the monitoring of diabetics using HbA1c.Methods: The study enrolled 9,792 Tunisian diabetic patients. HbA1c was measured by cation-exchange highpressure liquid chromatography (HPLC). All the chromatograms were analyzed for the presence of Hbvariants.Results: We identified 228 cases (2.33%) of Hb variants with D-10 HPLC (Bio-Rad): 191 with HbA/S trait, 27 with HbA/C trait, and 10 hemoglobin variants with the mention ‘Variant-Window’ on the chromatograms and subsequently identified as HbA/S on Variant I HPLC (Bio-Rad). Thus, the prevalence of HbS was 2.05%. We did not find any homozygous variant. All HbA1c results were reported to the treating physician.Conclusions: To evaluate glycated hemoglobin in populations with a high prevalence of hemoglobinopathies, we should use the HPLC method, which is easy, economical, and reliable. Based on an algorithm, hemoglobinvariants visualized on HPLC should be reported to the physician to improve the management of patients.Keywords: hemoglobinopathies; HbA1c; HPLC; diabetes mellitus; prevalence; Tunisi

Rumen fermentation pattern and blood metabolites of lambs from three breeds reared on pasture or feedlot

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A New Approach To Light-Weight Ablators Analysis: From Micro-Tomography Measurements to Statistical Analysis and Modeling

The morphology characteristics and ablation behavior of a highly porous carbon fiber preform are studied using a combined experimental/numerical approach. Morphological characterization of the three-dimensional structure of the material is performed by hard X-rays synchrotron micro-tomography at the Advanced Light Source of Lawrence Berkeley National Laboratory. The resulting micro-tomography voxels are used to compute geometrical properties of the carbon preform, like porosity, specific surface area and tortuosity, that are otherwise indirectly measured through experimental techniques. The reconstructed volumes are used to build a computational grid for numerical simulations of the fibers\u27 ablation. By modeling the diffusion of oxygen through the porous medium using Lagrangian methods, and the oxidation at the carbon fibers\u27 surface using a reactivity model, the ablation of the carbon fibers are simulated for a range of Thiele numbers. It is shown that in the diffusion limited regime (large Thiele number), the ablation of the fibers occurs at the surface of the material. In the reaction limited regime (low Thiele number), the oxygen penetrates into the fibers, resulting in volumetric ablation and high material spallation

Risk Factors for Death in Children with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a deadly disease caused by a protozoan called Leishmania. It is transmitted to humans from infected animals by a sandfly bite. Most people actually manage to control the infection and do not get sick, while others develop a range of symptoms. VL impairs the production of blood components and causes the immune system to malfunction, thus anemia, bleeding, and bacterial infections often complicate the disease and can lead to death. To identify risk factors for death from VL, the authors studied 546 children in a referral center in Recife, Brazil. They looked at clinical history, physical examination and full blood counts on the assumption these could be easily assessed in peripheral health facilities. They found that the presence of fast breathing, jaundice, mucosal (e.g. gum) bleeding and bacterial infections would each increase the risk of death in three to four-fold. The presence of very low counts of neutrophils and platelets would increase the risk of death in three and 12-fold respectively. This knowledge can help clinicians to anticipate the use of antibiotics or transfusion of blood products in high risk patients, who would potentially benefit from transfer to centers with advanced life support facilities

Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma

Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.National Institutes of Health (U.S.) (U54 CA210180)MIT/Mayo Physical Sciences Center for Drug Distribution and Drug Efficacy in Brain TumorsDana-Farber Cancer Institute (PLGA Fund)Lundbeck FoundationNovo Nordisk Foundatio

A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma

Head and neck squamous cell carcinoma (SCC) remains among the most aggressive human cancers. Tumour progression and aggressiveness in SCC are largely driven by tumour-propagating cells (TPCs). Aerobic glycolysis, also known as the Warburg effect, is a characteristic of many cancers; however, whether this adaptation is functionally important in SCC, and at which stage, remains poorly understood. Here, we show that the NAD+-dependent histone deacetylase sirtuin 6 is a robust tumour suppressor in SCC, acting as a modulator of glycolysis in these tumours. Remarkably, rather than a late adaptation, we find enhanced glycolysis specifically in TPCs. More importantly, using single-cell RNA sequencing of TPCs, we identify a subset of TPCs with higher glycolysis and enhanced pentose phosphate pathway and glutathione metabolism, characteristics that are strongly associated with a better antioxidant response. Together, our studies uncover enhanced glycolysis as a main driver in SCC, and, more importantly, identify a subset of TPCs as the cell of origin for the Warburg effect, defining metabolism as a key feature of intra-tumour heterogeneity