Probabilistic topic modelling in food spoilage analysis: A case study with Atlantic salmon (Salmo salar).

Probabilistic topic modelling is frequently used in machine learning and statistical analysis for extracting latent information from complex datasets. Despite being closely associated with natural language processing and text mining, these methods possess several properties that make them particularly attractive in metabolomics applications where the applicability of traditional multivariate statistics tends to be limited. The aim of the study was thus to introduce probabilistic topic modelling - more specifically, Latent Dirichlet Allocation (LDA) - in a novel experimental context: volatilome-based (sea) food spoilage characterization. This was realized as a case study, focusing on modelling the spoilage of Atlantic salmon (Salmo salar) at 4 °C under different gaseous atmospheres (% CO2/O2/N2): 0/0/100 (A), air (B), 60/0/40 (C) or 60/40/0 (D). First, an exploratory analysis was performed to optimize the model tunings and to consequently model salmon spoilage under 100% N2 (A). Based on the obtained results, a systematic spoilage characterization protocol was established and used for identifying potential volatile spoilage indicators under all tested storage conditions. In conclusion, LDA could be used for extracting sets of underlying VOC profiles and identifying those signifying salmon spoilage, giving rise to an extensive discussion regarding the key points associated with model tuning and/or spoilage analysis. The identified compounds were well in accordance with a previously established approach based on partial least squares regression analysis (PLS). Overall, the outcomes of the study not only reflect the promising potential of LDA in spoilage characterization, but also provide several new insights into the development of data-driven methods for food quality analysis.

Spoilage evaluation of raw Atlantic salmon (Salmo salar) stored under modified atmospheres by multivariate statistics and augmented ordinal regression.

The development of quality monitoring systems for perishable food products like seafood requires extensive data collection under specified packaging and storage conditions, followed by advanced data analysis and interpretation. Even though the benefits of using volatile organic compounds as food quality indices have been recognized, few studies have focused on real-time quantification of the seafood volatilome and subsequent systematic identification of the most important spoilage indicators. In this study, spoilage of Atlantic salmon (Salmo salar) stored under modified atmospheres (% CO2/O2/N2) and air was characterized by performing multivariate statistical analysis and augmented ordinal regression modelling for data collected by microbiological, chemical and sensory analyses. Out of 25 compounds quantified by selected-ion flow-tube mass spectrometry, ethanol, dimethyl sulfide and hydrogen sulfide were found characteristic under anaerobic conditions (0/0/100 and 60/0/40), whereas spoilage under air was primarily associated with the production of alcohols and ketones. Under high-O2 MAP (60/40/0), only 3-methylbutanal fulfilled the identification criteria. Overall, this manuscript presents a systematic and widely applicable methodology for the identification of most potential seafood spoilage indicators within the context of intelligent packaging technology development. In particular, parallel application of statistics and modelling was found highly beneficial for the performance of the quality characterization process and for the practical applicability of the obtained results in food quality monitoring.

Novel Oxazolidinone-Based Peroxisome Proliferator Activated Receptor Agonists: Molecular Modeling, Synthesis, and Biological Evaluation.

A series of new peroxisome proliferator activated receptors (PPARs) chiral ligands have been designed following the accepted three-module structure comprising a polar head, linker, and hydrophobic tail. The majority of the ligands incorporate the oxazolidinone moiety as a novel polar head, and the nature of the hydrophobic tail has also been varied. Docking studies using the crystal structure of an agonist bound to the ligand binding domain of the PPARα receptor have been performed as a tool for their design. Suitable synthetic procedures have been developed, and compounds with different stereochemistries have been prepared. Evaluation of basal and ligand-induced activity proved that several compounds showed agonist activity at the PPARα receptor, thus validating the oxazolidinone template for PPAR activity. In addition, two compounds, 2 and 4, showed dual PPARα/PPARγ agonism and interesting food intake reduction in rats.

Synthesis of nonadeuterated 1α,25-dihydroxyvitamin D2.

An efficient convergent synthesis of nonadeuterated 1α,25-dihydroxyvitamin D2 (1) by Pd(0)-catalyzed coupling between the boronate ester (upper fragment) and the enol triflate (A-ring fragment) is described. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors.

The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research.

Acquired ichthyosis as a paraneoplastic syndrome in Hodgkin's disease

An 80-year-old man was admitted to hospital with low-grade fever, weight loss, asthenia and anorexia. Physical examination revealed generalised ichthyosis with palmoplantar hyperkeratosis. CT scan showed retroperitoneal and inguinal lymph node enlargement. An inguinal lymph node biopsy revealed Hodgkin's disease (nodular-sclerosing subtype). The patient received chemotherapy, showing a clear improvement of both skin lesions and lymph nodes (AU)

Prevalence of metabolic syndrome in Galicia (NW Spain) on four alternative definitions and association with insulin resistance.

The present study evaluated the prevalence of the metabolic syndrome (MS) in a representative sample (no.=2860) of adults from the Spanish region of Galicia using the definitions of a) the World Health Organization; b) the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; c) the European Group for Study of Insulin Resistance; and d) the International Diabetes Federation. In addition, we assess concordance among the different definitions, and the relationships of MS with insulin resistance (IR) as assessed by the homeostatic model assessment (HOMA-IR) index. Our results indicate a high prevalence of MS under all 4 definitions. MS prevalence was higher in men than women on all 4 definitions, and increased significantly with body mass index and age. IR was high among subjects with MS, and the HOMA index was a good discriminator of MS and non-MS on all 4 definitions, suggesting that HOMA index may be a useful predictive tool in clinical practice.

Primary ovarian Burkitt lymphoma

Primary ovarian Burkitt lymphoma (BL) is a rare neoplasm in adults. We report a 30-year-old woman diagnosed with primary bilateral ovarian BL. She presented features of a twisted ovarian cyst and underwent bilateral salpingo-oophorectomy. The histopathologic evaluation yielded the diagnosis of BL and subsequently she received chemoimmunotherapy with CODOX-M-IVAC plus rituximab (anti-CD20 monoclonal antibody) (AU)

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[Adrenal failure caused by primary adrenal non-Hodgkin lymphoma: a case report and review of the literature]. / Insuficiencia suprarrenal causada por un linfoma no-Hodgkin B primario suprarrenal: presentación de un caso y revisión de la literatura.

We report a case of 78-year old man who presented with symptoms of adrenal insufficiency. The computed tomography (CT) scan showed the presence of bilateral adrenal masses. A CT-scan guided needle biopsy revealed diffuse large- B cell lymphoma. The absence of pathological findings in clinical, bone marrow and CT scan examinations supported the diagnosis of primary non-Hodgkin Lymphoma of the adrenal glands. The patient was treated with four cycles of R-CHOP chemotherapy with Rituximab, liposomal Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone. At the end of fourth cycle there was radiological improvement but the chemotherapy was stopped because of IV grade toxicity. He completed treatment with radiotherapy of right adrenal mass. Few days after finishing radiation therapy the patient died due to a disseminated infection. No progressive disease was founded.

Insuficiencia suprarrenal causada por un linfoma no-Hodgking B primario suprarrenal: presentación de un caso y revisión de la literatura / Adrenal failure caused by primary adrenal non-hodking lymphoma: a case report and review of the literature

Presentamos el caso de un varón de 78 años que ingresa por un cuadro de debut de insuficiencia suprarrenal. Se realizó un estudio TC que mostró masas suprarrenales bilaterales de hasta 10 cm. Se completó estudio con biopsia percutanea de masa suprarrenal y biopsia de médula ósea, siendo diagnosticado de Linfoma no Hodgkin B difuso de células grandes primario suprarrenal con afectación suprarrenal bilateral. El paciente fue tratado con quimioterapia según esquema R-CHOP (Rituximab, Ciclofosfamida, Doxorrubicina liposomal, Vincristina y Prednisona).Tras 4 ciclos de quimioterapia se objetivo una respuesta parcial radiológica. Se suspendió la quimioterapia por toxicidad grado IV, completándose el tratamiento con RT sobre masa suprarrenal derecha. El paciente falleció por cuadro séptico pocos días después de finalizar la radioterapia, sin objetivarse progresión de la enfermedad

We report a case of 78-year old man who presented with symptoms of adrenal insufficiency. The computed tomography (CT) scan showed the presence of bilateral adrenal masses. A CT-scan guided needle biopsy revealed diffuse large- B cell lymphoma. The absence of pathological findings in clinical bone marrow and CT scan examinations supported the diagnosis of Lymphoma of the adrenal glands.The patient was treated with four cycles of R-CHOP chemotherapy with Rituximab, liposomal Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone. At the end of fourth cycle there was radiological improvement but the chemotherapy was stopped because of IV grade toxicity. He completed treatment with radiotherapy of right adrenal mass. Few days after finishing radiation therapy the pacient died due to a disseminated infection. No progressive disease was founded

Combined therapy with rituximab plus cyclophosphamide/vincristine/prednisone for Sjogren's syndrome-associated B-cell non-Hodgkin's lymphoma.

Sjogren's syndrome (SS) is characterized by an increased risk of developing non-Hodgkin's lymphoma (NHL). Optimal treatment for NHL-complicating SS is not clearly established. NHL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We report clinical and immunological data of a patient with SS and NHL who was treated with a regimen consisting of cyclophosphamide/vincristine/prednisone (CVP) plus rituximab. A 68-year-old women had a 26-year history of SS and autoimmune thyroiditis. The clinical course of SS was complicated with severe splenomegaly. An increased percentage of CD19+ B cells (up to 30%) was detected in peripheral blood during follow-up. Clonal rearrangement of immunoglobulin heavy chain was detected. Low-grade B marginal zone lymphoma was diagnosed (peripheral blood immunophenotype: CD19+CD20+CD23+sIg+Kappa; bone marrow immunophenotype: 25% lymphocytes; CD19+CD20+CD79A/BCL2+). She received a total of six cycles of CVP plus rituximab (375 mg/m2). Therapy was well tolerated, and B lymphocytes were depleted from the peripheral blood. Splenomegaly normalized. No evidence of neoplastic infiltration was detected in bone marrow after completion of therapy, while certain symptoms of SS (sicca and arthralgia) improved with treatment. CVP plus rituximab proved effective in a patient with SS with NHL.

Prevalence, awareness, treatment and control of hypertension in Galicia (Spain) and association with related diseases.

The present study evaluated the prevalence of hypertension (HT) and its possible relationships with various risk factors in a representative sample (n=2884) of the adult population (>18 years old) of Galicia, a region of Spain. Subjects were selected by a two-step cluster sampling procedure from the Galician public health service database, which covers more than 95% of the population (2.7 million inhabitants). The overall prevalence of HT, defined as BP >140/90 mm Hg and/or current treatment with antihypertensive medication, was 25.5%, higher in men (31.1%) than in women (20.7%). Of the hypertensive subjects 50.6% were aware of the HT; of these, 72.0% were receiving treatment and 36.4% were treated and controlled. The prevalence of HT increased with age and was higher in subjects from urban areas than rural areas and higher in subjects with low educational level. Surprisingly, people with low educational level more frequently showed awareness of HT than people with high education level. Increased body mass index was related to increased prevalence of HT and close associations were observed between HT and cardiovascular diseases. Our data also show a linear upward trend in blood pressure from normal glucose metabolism to diabetes mellitus. Surprisingly, the prevalence of HT among people with known diabetes was higher than among people with undetected diabetes, which may indicate poor control of HT in diabetic subjects.

Vitamin D, Pit-1, GH, and PRL: possible roles in breast cancer development.

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the most active metabolite of vitamin D, exerts its biological effects by binding to a specific intracellular receptor (the vitamin D receptor, VDR) present in target cells. 1,25-(OH)(2)D(3) is involved in a host of cell processes, including calcium homeostasis, cell growth and differentiation, and secretion of hormones. Several studies have explored the role of 1,25-(OH)(2)D(3) in cell growth and differentiation in normal and tumoral mammary gland, in which it shows antiproliferative effects. These effects have been attributed to suppression of growth-stimulatory signals and potentiation of growth-inhibitory signals, leading to changes in cell-cycle regulators as well as to induction of apoptosis. In apparent contrast to these antiproliferative effects, however, several studies have suggested that breast tumor formation may be related to the autocrine/paracrine effects of growth hormone (GH) and prolactin (PRL). The pituitary transcription factor-1 (Pit-1), which in the pituitary is critical to both cell differentiation and PRL and GH transcription, has been recently found in normal and tumoral human breast tissue, with mRNA expression levels significantly higher in tumors than in normal breast. As in the pituitary, Pit-1 regulates mammary GH and PRL secretion, increases cell proliferation and decreases apoptosis. 1,25-(OH)(2)D(3) administration to the MCF-7 human breast adenocarcinoma cell line significantly reduces Pit-1 expression, suggesting that inhibition of Pit-1 expression by 1,25-(OH)(2)D(3) may reduce the increase in proliferation induced by this transcription factor directly or indirectly through increased GH and/or PRL expression. In this review, we evaluate the role of 1,25-(OH)(2)D(3) and Pit-1/PRL/GH in human breast, and consider the relationships between these factors in normal mammary development and in breast cancer.

Independent predictors of renal dysfunction after heart transplantation in patients with normal pretransplant renal function.

BACKGROUND: Renal dysfunction (RD) is a common complication after heart transplantation (HT), but predictors of post-HT RD have not been clearly identified. METHODS: We studied 262 HT patients (mean age 54 years, 221 men) with normal baseline renal function. Potential risk factors examined were age, sex, pre-HT ischemic cardiomyopathy, pre- and post-HT diabetes mellitus, pre- and post-HT arterial hypertension, initial immunosuppressive protocol (before 1998 [high cyclosporine, azathioprine, and prednisone] vs after 1998 [low cyclosporine, mycophenolate mofetil, and prednisone]), occurrence of rejection episodes > or =ISHLT Grade 3A, and creatinine level 1 month after HT. RD was considered mild if creatinine level was 1.5 to 2.5 mg/dl, moderate if creatinine level was >2.5 mg/dl, and severe if dialysis or kidney transplant was required. RESULTS: The cumulative incidence of RD (creatinine >1.5 mg/dl) was 35% at 12 months, 42% at 24 months, and 47% at 60 months (mean follow-up 59 +/- 31 months). Only 1% of patients had severe RD 60 months after HT. Independent predictors of RD 24 months after HT were older age (odds ratio [OR] 1.1 [95% confidence interval (95% CI) 1.0-1.1]; p = 0.001), male sex (OR 3.3 [95% CI 1.3-8.1]; p = 0.008), pre-1998 immunosuppressive protocol (OR 2.8 [95% CI 1.4-5.4]; p = 0.003), and creatinine level 1 month after HT (OR 3.2 [95% CI 1.0-5.4]; p < 0.0001). CONCLUSIONS: The cumulative incidence of RD in HT patients treated with calcineurin inhibitors increased with time after HT. Age, male sex, an immunosuppressive protocol with relatively high cyclosporine levels and creatinine level 1 month after HT were independent predictors of the presence of RD 24 months after HT.

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.

BACKGROUND: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported. OBJECTIVE: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation. METHODS: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine. RESULTS: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation. CONCLUSIONS: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.

Association between vitamin D receptor FokI. Polymorphism and serum parathyroid hormone level in patients with chronic renal failure.

We investigated the relationship between vitamin D receptor (VDR) start codon polymorphism and serum levels of PTH, calcidiol, and calcium in 64 Spanish patients with chronic renal failure (CRF). An exon 2 fragment of the VDR gene was amplified by PCR, and cleaved with the restriction enzyme FokI. The alleles were identified according to the digestion pattern obtained as F (absence of restriction site) and f (presence of restriction site). Genotype frequencies in the patient population were 54.7% FF, 28.1% Ff and 17.2% ff, vs 46.7% FF, 43.3% Ff and 10% ff in a healthy control population. The difference between the two populations was statistically significant (p<0.01). Within the patient population, mean serum PTH level in the FF group was significantly higher (159.77+/-25.69 pg/ml) than in both the Ff and ff groups (106.67+/-19.07 and 77.55+/-15.85 pg/ml, respectively; p<0.05). However there were no significant differences in serum levels of calcidiol or calcium among genotypes. These results suggest that FokI polymorphisms of the VDR gene may determine parathyroid response in CRF patients.

In-vitro anti-inflammatory activity of Pinus sylvestris and Plantago lanceolata extracts: effect on inducible NOS, COX-1, COX-2 and their products in J774A.1 murine macrophages.

Extracts of the plant species Pinus sylvestris L. and Plantago lanceolata L. have been used in traditional medicine for the treatment of certain respiratory diseases, but little is known about their precise effects and mechanisms of action. In this study, we investigated the effect of these plant extracts on the production of nitric oxide (NO) and prostaglandin E(2), NO synthase (NOS) type II, cyclooxygenase-1 (COX-1) and COX-2 mRNA expression in the murine macrophage cell line J774A.1. We found that Pinus sylvestris and Plantago lanceolata extracts inhibited NO production in a concentration-dependent manner in this cell line, without obvious cytotoxic effects as tested by MTT assay. The Plantago lanceolata extract at all doses used, and the Pinus sylvestris extract at high doses, showed significant scavenging of NO radicals released by the NO donor PAPA-NONOate. Our data also show that pre-treatment with these extracts significantly inhibits inducible NOS (iNOS) mRNA production in this cell line, without affecting COX-1 mRNA expression. COX-2 mRNA levels and PGE(2) levels induced by lipopolysaccharide/interferon-gamma were not modified upon pre-treatment with the extracts. Thus, our results suggest that the anti-inflammatory properties of Pinus sylvestris and Plantago lanceolata extracts may reflect decreased NO production, possibly due to inhibitory effects on iNOS gene expression or to NO-scavenging activity.

Analysis of the vitamin D receptor Fokl polymorphism.

In the present study we analysed the vitamin D receptor (VDR) Fokl polymorphism distribution in a Caucasian population from the North-West of Spain. This polymorphism has been associated with variation in bone mineral density levels and has been proposed as a factor for the genetic predisposition to osteoporosis. This study was performed in 60 healthy individuals by restriction fragment length polymorphism (RFLP) analysis using the endonuclease Fokl and alternatively using single strand conformation polymorphism (SSCP). The genotype distribution was: 46.7% FF homozygotes, 43.3% Ff heterozygotes, and 10% ff homozygotes. These values do not reveal significant differences in comparison with other available Caucasoid populations, but show clear differences with respect to African-American populations. The analysis of this polymorphism by SSCP reveals the existence of a novel single nucleotide polymorphism (AAT/AAC) located within the DNA binding domain of the VDR gene at position-19 codon. Thus, using a novel 109 bp hVDR gene fragment which excludes the AAT/AAC variant in the vitamin D receptor Fokl allows an easier determination by SSCP analysis of the Fokl polymorphism.

Effect of an integral suspension of Lepidium latifolium on prostate hyperplasia in rats.

This paper studies the effect of an integral suspension of Lepidium latifolium on experimental induced prostate hyperplasia, in rats. Oral treatment with 0.86 mg kg(-1) day(-1) for 6 months, significantly reduced prostate size and volume in castrated rats where the hyperplasia were induced by steroid treatment.

In-vitro anti-inflammatory effect of Eucalyptus globulus and Thymus vulgaris: nitric oxide inhibition in J774A.1 murine macrophages.

It is well known that nitric oxide (NO) plays an important role in the pathogenesis of inflammatory diseases. Eucalyptus globulus Labill. and Thymus vulgaris L. have been used in traditional medicine in the treatment of bronchitis, asthma and other respiratory diseases. The present study focuses on the effects of these two extracts on NO production induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in the murine macrophage cell line J774A.1. In addition, cell viability, scavenging activity and inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. E. globulus and T. vulgaris extracts significantly inhibited the enhanced production of NO induced by LPS and IFN-gamma in a dose-dependent manner. Treatment with these two extracts did not reduce cell viability at any dose used. Both plant extracts showed significant scavenging of NO radicals released by an NO donor, PAPA-NONOate. Results also show that pre-treatment with E. globulus and T. vulgaris extracts significantly inhibits iNOS mRNA expression. This study thus suggests that the inhibition of net NO production by these two extracts may be due to their NO scavenging activity and/or their inhibitory effects on iNOS gene expression.