Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.

Background: Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. Case series: The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. Conclusion: In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release

Flood vulnerability, environmental land use conflicts, and conservation of soil and water: a study in the Batatais SP municipality, Brazil.

In many regions across the planet, flood events are now more frequent and intense because of climate change and improper land use, resulting in risks to the population. However, the procedures to accurately determine the areas at risk in regions influenced by inadequate land uses are still inefficient. In rural watersheds, inadequate uses occur when actual uses deviate from land capability, and are termed environmental land use conflicts. To overcome the difficulty to evaluate flood vulnerability under these settings, in this study a method was developed to delineate flood vulnerability areas in a land use conflict landscape: the Batatais municipality, located in the State of São Paulo, Brazil. The method and its implementation resorted to remote sensed data, geographic information systems and geo-processing. Satellite images and their processing provided data for environmental factors such as altitude, land use, slope, and soil class in the study area. The importance of each factor for flood vulnerability was evaluated through the analytical hierarchy process (AHP). According to the results, vast areas of medium to high flood vulnerability are located in agricultural lands affected by environmental land use conflicts. In these areas, amplified flood intensities, soil erosion, crop productivity loss and stream water deterioration are expected. The coverage of Batatais SP municipality by these vulnerable areas is so extensive (60%) that preventive and recovery measures were proposed in the context of a land consolidation-water management plan aiming flood control and soil and water conservation

Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins

The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic receptor are under debate. We report that PrPC interacts with vitronectin but not with fibronectin or collagen. the binding sites mediating this PrPC-vitronectin interaction were mapped to residues 105-119 of PrPC and the residues 307-320 of vitronectin. the two proteins were co-localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin addition to cultured dorsal root ganglia induced axonal growth, which could be mimicked by vitronectin peptide 307-320 and abrogated by anti-PrPC antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrPC-null mice. Functional assays demonstrated that relative to wild-type cells, PrPC-null dorsal root neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding site), and exhibited greater alpha v beta 3 activity. Our findings indicate that PrPC plays an important role in axonal growth, and this function may be rescued in PrPC-knockout animals by integrin compensatory mechanisms.Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, São Paulo, BrazilUniv São Paulo, Inst Quim, Dept Bioquim, BR-05508 São Paulo, BrazilHosp Canc, Ctr Tratamento & Pesquisa, São Paulo, BrazilUniv Fed Parana, Dept Patol Basica, BR-80060000 Curitiba, Parana, BrazilUniv Fed Parana, Dept Biol Celular, BR-80060000 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, INFAR, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, INFAR, BR-04023062 São Paulo, BrazilWeb of Scienc

Semaphorins and their receptors: Novel features of neural guidance molecules

Semaphorins were originally identified as axon guidance cues involved in the development of the nervous system. In recent years, it is emerging that they also participate in various biological systems, including physiological and pathological processes. In this review, we primarily focus on our cumulative findings for the role of semaphorins and their receptors in the regulation of the immune system, while also summarizing recent progress in the context of cardiovascular system

New species of Hasemania (Characiformes: Characidae) from Central Brazil, with comments on the endemism of upper rio Tocantins basin, Goiás State

Hasemania kalunga é descrita para a bacia do alto rio Tocantins, Chapada dos Veadeiros, Goiás, Brasil. A espécie nova distingue-se das suas congêneres pelo número de escamas perfuradas da linha lateral (11-21 vs. 5-9, exceto de H. crenuchoides e H. piatan), pela presença de uma mancha umeral preta e verticalmente alongada (vs. ausência, exceto de H. crenuchoides, H. nambiquara e H. piatan), e pela ausência de escamas na base da nadadeira anal (vs. presença, exceto de H. maxillaris e H. piatan), por 19 raios principais na nadadeira caudal (vs.18 em H. piatan). Ela também difere de H. crenuchoides por dados morfométricos. A ausência de uma bainha de escamas cobrindo a base da nadadeira anal, um caráter incomum em Characidae, e o endemismo da ictiofauna do alto rio Tocantins são discutidos.Hasemania kalunga is described from the upper rio Tocantins basin, Chapada dos Veadeiros, Goiás State, Brazil. The new species is distinguished from its congeners by the number of perforated lateral line scales (11-21 vs. 5-9, except from H. crenuchoides and H. piatan), by the presence of a black vertically-elongate humeral spot (vs. absent, except from H. crenuchoides, H. nambiquara, and H. piatan), and by absence of scale sheath along anal-fin base (vs. presence, except from H. maxillaris, and H. piatan), by 19 principal caudal-fin rays (vs. 18 in H. piatan). It differs also from H. crenuchoides by morphometric data. The absence of scale sheath covering the anal-fin base, an uncommon character in Characidae, and the endemism of the ichthyofauna from the upper rio Tocantins are discussed