Factors Affecting Fasting Urinary Calcium Excretion in Stone Former Patients on Different Dietary Calcium Intake

The effects of variable calcium content on daily and fasting urinary calcium and other lithogenic solutes excretion, on the bone turnover index (fasting hydroxyproline urinary excretion) and on the calciotropic hormones were studied in 312 stone former patients with an outpatient protocol and 15 stone former patients in an inpatient study. Furthermore in 60 of these patients, 30 while on a low calcium diet (LCD) and 30 on a free calcium home diet (FCD), the effects of an oral calcium load (OCL) on bone turnover index, calciotropic hormones and calcium excretion were evaluated. The results demonstrate that an LCD is effective in reducing daily calcium excretion. Fasting calcium excretion is apparently not affected by changes in dietary calcium content. On the other hand, LCD induces a marked increase in bone resorption, without apparent signs of increased parathyroid activity. This may explain the failure to reduce fasting urinary calcium excretion by the LCD. The OCL greatly reduced bone resorption rate, without any change in calciotropic hormones, especially in patients on LCD. In conclusion, the LCD induces a reduction in the lithogenic factors in the urine of stone formers, but induces a marked increase in bone resorption. The lack of any change in fasting urinary calcium excretion in conditions of different dietary calcium intake may be due to an opposite change in the intestinal and osseous components that affect this parameter, and is therefore of little value

Nuclear factor kB as a target for new drug development in myeloid malignancies.

The transcription nuclear factor k B (NF-kB) can intervene in oncogenesis through to its capacity to regulate the expression of a large number of genes that regulate apoptosis, cell proliferation and differentiation as well as inflammation, angiogenesis and tumor migration. Impaired NF-kB activity has been demonstrated not only in solid cancers but also in various types of hematologic malignancies including acute myeloid leukemia, chronic myelogenous leukemia and in a subset of myelodysplastic syndromes. The underlying mechanisms, illustrated in the text and although quite diverse in different diseases, provide the rationale for new therapeutic strategies combining different NF-kB or proteasome inhibitors. It has, therefore, been proposed that inhibition of NF-kB could be an adjuvant therapy for cancer and many phase I/II clinical studies are ongoing with different inhibitors. This review highlights the in vitro and in vivo results of NF-kB inhibition in myeloid malignancies

Carbon dots conjugated to SN38 for improved colorectal anticancer therapy

Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically con-verted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged

PROGRAMA DE EDUCAÇÃO PELO TRABALHO: RELATO DE EXPERIÊNCIA SOBRE A FORMAÇÃO DE TRABALHADORES

The present study aims to report the experience of students and lecturers on the Work-based Learning Program in the health services network in a municipality in the South of Brazil in 2012, focussing on actions of training of the Unified Health System (SUS) workers. The program was participated in by students from the physiotherapy and nursing courses, who undertook actions so as to meet the needs of the services from the areas of Mental Health, Primary Care and General Hospital. The results converge on the need for training of the professionals of the network and for encouraging Continuous Education in Health Policy. It is concluded that the Program has importance for the teaching, service, management and community, bearing in mind the global perception of the benefits and results created in the care network in the municipality.O presente estudo objetiva relatar a experiência de discentes e docentes no Programa de Educação pelo Trabalho na rede de serviços de saúde de um município do Sul do Brasil no ano de 2012, enfocando ações de formação dos trabalhadores do Sistema Único de Saúde. O Programa contou com a participação de alunos dos cursos de fisioterapia e da enfermagem que desenvolveram ações no sentido de atender as necessidades dos serviços da área de Saúde Mental, Atenção Básica e do Hospital Geral. Os resultados convergem para a necessidade de formação dos profissionais da rede e ao fomento à Política de Educação Permanente em Saúde. Conclui-se sobre a importância do Programa para o ensino, serviço, gestão e comunidade, tendo em vista a percepção global dos benefícios e resultados gerados na rede de atenção no município

Revisiting Attenuation Curves: the Case of NGC 3351

Multi-wavelength images from the farUV (~0.15 micron) to the sub-millimeter of the central region of the galaxy NGC 3351 are analyzed to constrain its stellar populations and dust attenuation. Despite hosting a ~1 kpc circumnuclear starburst ring, NGC 3351 deviates from the IRX-beta relation, the relation between the infrared-to-UV luminosity ratio and the UV continuum slope (beta) that other starburst galaxies follow. To understand the reason for the deviation, we leverage the high angular resolution of archival nearUV-to-nearIR HST images to divide the ring into ~60-180 pc size regions and model each individually. We find that the UV slope of the combined intrinsic (dust-free) stellar populations in the central region is redder than what is expected for a young model population. This is due to the region's complex star formation history, which boosts the nearUV emission relative to the farUV. The resulting net attenuation curve has a UV slope that lies between those of the starburst attenuation curve (Calzetti et al. 2000) and the Small Magellanic Cloud extinction curve; the total-to-selective attenuation value, R'(V)=4.93, is larger than both. As found for other star-forming galaxies, the stellar continuum of NGC 3351 is less attenuated than the ionized gas, with E(B-V)_{star}=0.40 E(B-V)_{gas}. The combination of the `red' intrinsic stellar population and the new attenuation curve fully accounts for the location of the central region of NGC 3351 on the IRX-beta diagram. Thus, the observed characteristics result from the complex mixture of stellar populations and dust column densities in the circumnuclear region. Despite being a sample of one, these findings highlight the difficulty of defining attenuation curves of general applicability outside the regime of centrally-concentrated starbursts.Comment: 45 page, 17 figures; accepted for publication on the Astrophysical Journal, March 21st, 202

The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRα-positive hypereosinophilic syndrome. Results of a multicenter prospective study

BACKGROUND AND OBJECTIVES: The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor a (PDGFRalpha) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRalpha tyrosine kinase. These cases with FIP1L1-PDGFRalpha rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. DESIGN AND METHODS: A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. RESULTS: Twenty-seven male patients carried the FIP1L1-PDGFRalpha rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15-60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. INTERPRETATION AND CONCLUSIONS: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRalpha rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses

CLusters in the Uv as EngineS (CLUES). II. Sub-kpc scale outflows driven by stellar feedback

We analyze the far-ultraviolet spectroscopy of 20 young and massive star clusters (YSCs) in 11 nearby star-forming galaxies. We probe the interstellar gas intervening along the line of sight, detecting several metal absorption lines of a wide range of ionization potentials, from 6.0 eV to 77.5 eV. Multiple-component Voigt fits to the absorption lines are used to study the kinematics of the gas. We find that nearly all targets in the sample feature gas outflowing from 30 up to 190 km per second, often both in the neutral and ionized phase. The outflow velocities correlate with the underlying stellar population properties directly linked to the feedback: the mass of the YSCs, the photon production rate and the instantaneous mechanical luminosity produced by stellar winds and SNe. We detect a neutral inflow in 4 targets, which we interpret as likely not associated with the star cluster but tracing larger scale gas kinematics. A comparison between the outflows energy and that produced by the associated young stellar populations suggests an average coupling efficiency of 10 per cent with a broad scatter. Our results extend the relation found in previous works between galactic outflows and the host galaxy star-formation rate to smaller scales, pointing towards the key role that clustered star formation and feedback play in regulating galaxy growth.Comment: Accepted for publication on the Astronomical Journal on 14th February 2024. 32 pages, 13 figure

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007. Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting. Methods: A prospective study was conducted in four Italian regions between 1 October 2013 and 30 June 2015. The study population included patients aged 65 18&nbsp;years undergoing hemodialysis and treated with epoetins as per the clinical practice of the participating centers. The two comparison cohorts included patients treated with either an originator or a biosimilar epoetin alfa. Each patient was followed up until occurrence of any safety outcome of interest (grouped into three major categories), switch to a different ESA product, transplant or peritoneal dialysis, death, or end of the study period, whichever came first. Results: Overall, 867 subjects were included in the study (originator: N = 423; biosimilar: N = 444). Biosimilar users were older than originator users (median age of 76 vs 64&nbsp;years, respectively), more frequently affected by arrhythmia (29.3 vs 22.5%), and less frequently candidates for transplantation (3.8 vs 18.2%). Cox-regression analysis showed no increase in risk of safety outcomes in biosimilar users, even after adjusting for confounding factors: 1.0 (95% confidence interval [CI] 0.7\u20131.3) for any outcomes; 1.1 (95% CI 0.7\u20131.8) for problems related to dialysis device; 0.9 (95% CI 0.6\u20131.5) for cardio- and cerebro-vascular conditions; 0.9 (95% CI 0.6\u20131.5) for infections. Conclusion: This study confirms the comparable safety profiles of originator and biosimilar epoetin alfa drugs when used in patients receiving dialysis

Notulae to the Italian native vascular flora: 8

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions for taxa in the genera Ajuga, Chamaemelum, Clematis, Convolvulus, Cytisus, Deschampsia, Eleocharis, Epipactis, Euphorbia, Groenlandia, Hedera, Hieracium, Hydrocharis, Jacobaea, Juncus, Klasea, Lagurus, Leersia, Linum, Nerium, Onopordum, Persicaria, Phlomis, Polypogon, Potamogeton, Securigera, Sedum, Soleirolia, Stachys, Umbilicus, Valerianella, and Vinca. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1