Treatment responses to antiangiogenetic therapy and chemotherapy in nonsecreting paraganglioma (PGL4) of urinary bladder with SDHB mutation: a case report

Paraganglioma (PGL) is a rare neuroendocrine tumor. Currently, the malignancy is defined as the presence of metastatic spread at presentation or during follow-up. Several gene mutations are listed in the pathogenesis of PGL, among which succinate dehydrogenase (SDHX), particularly the SDHB isoform, is the main gene involved in malignancy. A 55-year-old male without evidence of catecholamine secretion had surgery for PGL of the urinary bladder. After 1 year, he showed a relapse of disease and demonstrated malignant PGL without evidence of catecholamine secretion with a germline heterozygous mutation of succinate dehydrogenase B (SDHB). After failure of a second surgery for relapse, he started medical treatment with sunitinib daily but discontinued due to serious side effects. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapeutic regimen stopped the disease progression for 7 months. Conclusion: Malignant PGL is a very rare tumor, and SDHB mutations must be always considered in molecular diagnosis because they represent a critical event in the progression of the oncological disease. Currently, there are few therapeutic protocols, and it is often difficult, as this case demonstrates, to decide on a treatment option according to a reasoned set of choices. Abbreviations: CVD = cyclophosphamide, vincristine and dacarbazine, HIF-1a = hypoxia inducible factor 1 alpha, PGL = paraganglioma, SDH = succinate dehydrogenase, VEGF = vasoendothelial growth factor

A 31T split-pair pulsed magnet for single crystal x-ray diffraction at low temperature

We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction in magnetic fields up to 31T and at low temperature down to 1.5 K. The apparatus consists of a split-pair magnet, a liquid nitrogen bath to cool the pulsed coil, and a helium cryostat allowing sample temperatures from 1.5 up to 250 K. Using a 1.15MJ mobile generator, magnetic field pulses of 60 ms length were generated in the magnet, with a rise time of 16.5 ms and a repetition rate of 2 pulses/hour at 31 T. The setup was validated for single crystal diffraction on the ESRF beamline ID06

Can remote STI/HIV testing and eClinical Care be compatible with robust public health surveillance?

In this paper we outline the current data capture systems for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) surveillance used by Public Health England (PHE), and how these will be affected by the introduction of novel testing platforms and changing patient pathways. We outline the Chlamydia Online Clinical Care Pathway (COCCP), developed as part of the Electronic Self-Testing for Sexually Transmitted Infections (eSTI(2)) Consortium, which ensures that surveillance data continue to be routinely collected and transmitted to PHE. We conclude that both novel diagnostic testing platforms and established data capture systems must be adaptable to ensure continued robust public health surveillance

Obesity and bone loss at menopause: The role of sclerostin

Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 \ub1 3.9 years; BMI, 46.0 \ub1 4.2 kg/m2 ) and 28 BMI-matched post-menopausal women (age, 55.5 \ub1 3.8 years; BMI, 46.1 \ub1 4.8 kg/m2 ) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p < 0.001), femoral neck (p < 0.0001), and total skeleton (p < 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p < 0.01), while menopausal status significantly predicted BMD at total hip (p < 0.01), femoral neck (p < 0.001) and total body (p < 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p < 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre-and postmenopausal women, its potential actions in obesity require further investigation

Heat shock induced changes of adipokines gene expression in 3T3-L1 adipocytes

To study the effects of heat shock on adipokines gene expression 3T3-L1 adipocytes were used. Heat shock differently affected gene expression of leptin, adiponectin and acylation stimulating protein (ASP): exposure of cells to temperature higher than 39°C caused upregulation of leptin and downregulation of adiponectin and ASP genes. The present study provides the first evidence about the effects of heat shock on adipokines gene expression. Changes in gene expression of the three adipokines may help to explain the alteration of lipid metabolism and liver functionality occurring in animals exposed to hot conditions

Estimation of polycyclic aromatic hydrocarbons pollution in mediterranean sea from volturno river, southern italy: Distribution, risk assessment and loads

This study reports the data on the contamination caused by polycyclic aromatic hydrocarbons (PAHs) drained from the Volturno River. The seasonal and spatial distribution of PAHs in water and sediment samples was assessed. The 16 PAHs were determined in the water dissolved phase (DP), suspended particulate matter (SPM), and sediments. A multidimensional statistical approach was used to identify three pollution composite indicators. Contaminant discharges of PAHs into the sea were calculated in about 3158.2 kg/year. Total concentrations of PAHs varied in ranges 434.8 to 872.1 ng g−1 and 256.7 to 1686.3 ng L−1 in sediment samples and in water (DP + SPM), respectively. The statistical results indicated that the PAHs mainly had a pyrolytic source. Considering the sediment quality guidelines (SQGs), the water environmental quality standards (USEPA EQS), and risk quotient (RQ), the Volturno River would be considered as an area in which the environmental integrity is possibly at risk

Shubnikov-de Haas oscillations in YBa_2Cu_4O_8

We report the observation of Shubnikov-de Haas oscillations in the underdoped cuprate superconductor YBa$_2$Cu$_4$O$_8$ (Y124). For field aligned along the c-axis, the frequency of the oscillations is $660\pm 30$ T, which corresponds to $\sim 2.4$ % of the total area of the first Brillouin zone. The effective mass of the quasiparticles on this orbit is measured to be $2.7\pm0.3$ times the free electron mass. Both the frequency and mass are comparable to those recently observed for ortho-II YBa$_2$Cu$_3$O$_{6.5}$ (Y123-II). We show that although small Fermi surface pockets may be expected from band structure calculations in Y123-II, no such pockets are predicted for Y124. Our results therefore imply that these small pockets are a generic feature of the copper oxide plane in underdoped cuprates.Comment: v2: Version of paper accepted for publication in Physical Review Letters. Only minor changes to the text and reference

Metabolic and hormonal acclimation to heat stress in domesticated ruminants

Environmentally induced periods of heat stress decrease productivity with devastating economic consequences to global animal agriculture. Acclimatization is a process by which animals adapt to environmental conditions and engage behavioral, hormonal and metabolic changes that are characteristics of either acclimatory homeostasis or homeorhetic mechanisms used by the animals to survive in a new ‘physiological state’. These physiological modifications alter nutrient partitioning and may prevent heat-stressed lactating cows from recruiting glucose-sparing mechanisms. How these metabolic changes are initiated and regulated is not known. A better understanding of the adaptations enlisted by ruminants during heat stress is necessary to enhance the likelihood of developing strategies to simultaneously improve heat tolerance and increase productivity. Periodo prolungati di stress da caldo severo inducono effetti negative sulla produzione con conseguenze devastanti sulla economia del comparto agro-zootecnico. L’acclimatamento è un processo attraverso cui gli animali si adattano alla variazione delle condizioni ambientali modificando il loro comportamento e variano l’equilibrio ormonale e metabolico con meccanismi di tipo sia omeostatico sia omeoretico con lo scopo di sopravvivere alle nuove condizioni raggiungendo un nuovo stato fisiologico. Queste modificazioni fisiologiche alterano la ripartizione dei nutrienti e possono essere responsabili di una maggiore e diverso utilizzo del glucosio. Come queste variazioni e adattamenti metabolici hanno inizio non è ancora ben noto. Una migliore comprensione dei meccanismi di adattamento dei ruminanti alle condizioni di stress da caldo, permetterà di sviluppare strategie per contemporaneamente migliorare la termo tolleranza e la produttività di soggetti esposti a condizioni stressanti