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Although the Food and Drug Administration has authorized the marketing of “heat-not-burn” (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1β, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.

Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior.

Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, Salicornia europaea stands out as a promising edible plant. In this study, young and old S. europaea leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl4-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl4-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver’s drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia’s potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD.

Dental invagination or dens in dente is a rare malformation with a widely varied morphology. Radiographically, the affected tooth shows an infolding of the enamel and dentin that can extend to within the pulp cavity and the root and sometimes to the root apex. It can occur in both primary and permanent teeth, and its prevalence is reported to be 1.7% to 10%. The dental anomalies observed in association with dental invagination include taurodontia, microdontia, supernumerary teeth, gemination, and dentinogenesis imperfecta. This article presents a clinical case in which a radiographic finding could be compatible with the presence of a nasopalatine or globulomaxillary cyst and a dens in dente. It was decided to extract the invaginated tooth, and by 15 days postextraction, the radiolucid area had completely disappeared. The complex surgery that would have been required to remove the patient's supposed cyst was thus avoided. Clinical and radiographic examination is suggested before making further decisions that could complicate treatment when a lesion is associated with other dental anomalies. [ABSTRACT FROM AUTHOR]

El Cateterismo de Senos Petrosos Inferiores (CSSPPII) es una prueba útil para diferenciar entre el origen central y ectópico del síndrome de Cushing hormona adrenocorticotropa (ACTH)-dependiente. Presentamos el protocolo utilizado en nuestro centro y la evaluación de su rendimiento diagnóstico.

Bilateral inferior petrosal sinus sampling (BIPSS) is a useful test for differential diagnosis of central vs. ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (CS). We provide a description of the protocol used in our Center and an analysis of its diagnostic accuracy.

Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as “liquid e-cigarettes” (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the “heated tobacco products” (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk.

Active Points Test on auricle was renamed Needle Contact Test (or NCT), considered an extremely effective method to select most efficient auricle acupoint for Auricular Acupuncture (or AA) therapy. Our aims were to evaluate NCT efficiency as viable diagnostic option to identify the most appropriate AA acupoints to be selected for SupraSpinatus Tendinopathy (SST) associated shoulder pain treatment and to evaluate which auricle area has greater concentration of NCT positive acupoints in subjects with SST shoulder pain, comparing results with available AA ear maps. 45 subjects with SST diagnosis were enrolled. On 30 subjects in treatment group, NCT was performed on acupoints of the auricle shoulder representation areas (i.e., Scaphoid Fossa), while in 15 subjects of control group, NCT was performed on auricle areas not shoulder associated. Statistically significant lower Numeric Pain Rating Scale scores were seen for study group over time and compared to control. A small sample showed statistically significant increase of SST shoulder maximum abduction range of Movements. NCT identified best SST shoulder pain AA acupoints in Scaphoid Fossa (or SF1 and SF2). In conclusion NCT is a viable tool to efficiently identify the best AA acupoints in SST shoulder pain treatment.

The Food and Drug Administration has recently classified the IQOS electronic cigarette as a modified-risk tobacco product. However, IQOS cigarettes still release various harmful constituents typical of conventional cigarettes (CCs), although the concentrations are markedly lower. Here, we investigated the damaging effects of IQOS smoking on the liver. Male Sprague Dawley rats were exposed, whole body, 5 days/week for 4 weeks to IQOS smoke (4 sticks/day), and hepatic xenobiotic metabolism, redox homeostasis and lipidomic profile were investigated. IQOS boosted reactive radicals and generated oxidative stress. Exposure decreased cellular reserves of total glutathione (GSH) but not GSH-dependent antioxidant enzymes. Catalase and xanthine oxidase were greater in the exposed group, as were various hepatic CYP-dependent monooxygenases (CYP2B1/2, CYP1A1, CYP2A1, CYP2E1-linked). Respiratory chain activity was unaltered, while the number of liver mitochondria was increased. IQOS exposure had an impact on the hepatic lipid profile. With regard to the expression of some MAP kinases commonly activated by CC smoking, IQOS increased the p-p38/p38 ratio, while erythroid nuclear transcription factor 2 (Nrf2) was negatively affected. Our data suggest that IQOS significantly impairs liver function, supporting the precautionary stance taken by the WHO toward the use of these devices, especially by young people and pregnant women.

Oliver Higuera Gómez,1 Amaia Moreno Paul,2 Ana Laura Ortega Granados,3 Silverio Ros Martínez,4 Diego Pérez Parente,5 Pedro Ruiz Gracia,5 Lucía Sáenz Cuervo-Arango,6 Laia Vilà7 1Department of Medical Oncology, La Paz University Hospital, Madrid, Spain; 2Medical Oncology Department, Galdakao University Hospital, Galdakao, Spain; 3Medical Oncology Department, Hospital of Jaen, Jaen, Spain; 4Medical Oncology, Virgen de la Arrixaca University Hospital, Murcia, Spain; 5Lung Cancer, Medical Affairs Department, Roche Farma S.A, Madrid, Spain; 6Lung Cancer, Marketing Department, Roche Farma S.A, Madrid, Spain; 7Medical Oncology Department, Parc Taulí University Hospital, Sabadell, SpainCorrespondence: Oliver Higuera GómezDepartment of Medical Oncology, La Paz University Hospital, Paseo de la Castellana, 261, Madrid, 28046, SpainTel +34 91 727 11 38Email oliverhiguera@gmail.comPurpose: Identifying patient characteristics that define a worse disease prognosis or “high tumor burden” (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice.Patients and Methods: A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience.Results: HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively.Conclusion: In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.Keywords: non-small cell lung cancer, “high tumor burden”, number of metastases, tumor size, metastatic locations, lactate dehydrogenase

Planteamos una experiencia de formación, en el grado de Primaria, a partir de la lectura del libro de Paulo Freire “Cartas a quién pretende enseñar”, en diálogo con los relatos de experiencia escolar del alumnado. Con el formato de tertulia pensamos colectivamente junto a Freire. El proceso nos llevó a interpretar el funcionamiento de las instituciones escolares y el valor de la educación para la transformación del mundo, de los sujetos y de la sociedad. Repensar la escuela en diálogo con la historia, la del alumnado, de la mano de un referente de la pedagogía del silo XX.

Abstract A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men.

Summary: Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks. : Batth et al. use mass spectrometry-based phosphoproteomics to analyze receptor tyrosine kinase signaling activated by different ligands, identifying hundreds of differentially regulated phosphotyrosine sites. Tyrosine phosphatase Shp-2 regulates global tyrosine phosphorylation in a Pdgf-receptor-dependent manner, affecting cellular outcomes. Keywords: phosphoproteomics, Shp-2, PDGF, SHP099, Q exactive, orbitrap, label-free quantitation, tyrosine phosphorylation, TiO2, mass spectrometry

Abstract Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution rather than smoke and without tobacco combustion. Perceived as a safer alternative to conventional cigarettes, e-cigs are aggressively marketed as lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory guidelines. E-cigs have also gained popularity among never-smokers and teenagers, becoming an emergent public health issue. Despite the burgeoning worldwide consumption of e-cigs, their safety remains largely unproven and it is unknown whether these devices cause in vivo toxicological effects that could contribute to cancer. Here we demonstrate the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat lung model. We found that e-cigs have a powerful booster effect on phase-I carcinogen-bioactivating enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), and increase oxygen free radical production and DNA oxidation to 8-hydroxy-2′-deoxyguanosine. Furthermore, we found that e-cigs damage DNA not only at chromosomal level in peripheral blood, such as strand breaks in leucocytes and micronuclei formation in reticulocytes, but also at gene level such as point mutations in urine. Our results demonstrate that exposure to e-cigs could endanger human health, particularly among younger more vulnerable consumers.

Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders.

BACKGROUND:Obesity is recognized as a leading global health problem, correlated with an increased risk for several chronic diseases. One strategy for weight control management includes the use of vegetables rich in bioactive compounds to counteract weight gain, improve the antioxidant status and stimulate lipid catabolism. AIM OF THE STUDY:The aim of this study was to investigate the role of Raphanus sativus Sango sprout juice (SSJ), a Brassica extraordinarily rich in anthocyanins (AC) and isothiocyanates (ITCs), in a non-genetic model of obesity (high fat diet-HFD induced). METHODS:Control groups were fed with HFD or regular diet (RD). After a 10-week period, animals were assigned to experimental units and treated by gavage for 28 days as follows: HFD and RD control groups (rats fed HFD or RD and treated with vehicle only) and HFD-treated groups (rats fed HFD and treated with 15, 75 or 150 mg/kg b.w. of SSJ). Body weight and food consumption were recorded and serum lipid profile was measured (total cholesterol, triglycerides, and non-esterified fatty acids). Hepatic phase-I, phase-II as well as antioxidant enzymatic activities were assessed. RESULTS:SSJ lowered total cholesterol level, food intake and liver weight compared with HFD rodents. SSJ at medium dose proved effective in reducing body-weight (~19 g reduction). SSJ was effective in up-regulating the antioxidant enzymes catalase, NAD(P)H:quinone reductase, oxidised glutathione reductase and superoxide dismutase, which reached or exceeded RD levels, as well as the phase II metabolic enzyme UDP-glucuronosyl transferase (up to about 43%). HFD up-regulated almost every cytochrome P450 isoform tested, and a mild down-regulation to baseline was observed after SSJ intervention. CONCLUSION:This work reveals, for the first time, the antioxidant, hypolipidemic and antiobesity potential of SSJ, suggesting its use as an efficient new functional food/nutraceutical product.

Los tubérculos de la papa (Solanum tuberosum L.), al momentode la cosecha y por un tiempo determinado, se encuentran enestado dormante. La dormancia se induce con el inicio de latuberización y se define como un período en el cual no ocurreningún crecimiento visible de los brotes. Las hormonas vegetalesestán involucradas en todas las fases de progresión dela dormancia. Si bien el ácido abscísico (ABA) y el etileno sonnecesarios para su inducción, sólo el primero se requiere parasu mantenimiento. Los niveles de ABA se incrementan durantela formación de los tubérculos, se mantienen constantes durantela dormancia y disminuyen con el crecimiento activo de losbrotes. Un incremento en los niveles del ácido giberélico (AG )es necesario para inducir la formación del tubérculo, mientrasque una sensibilidad mayor a las citoquininas es determinantepara la pérdida de la dormancia. Cambios en los contenidos deácido indol acético (AIA ) y AG , están relacionados con la regulacióndel crecimiento del brote una vez se rompe la dormancia.Se ha comprobado que un factor importante, que contribuyetanto a la inducción de la tuberización como a la pérdida de ladormancia, es el flujo simplástico que controla la asignación deazúcares, el cual se inicia con un meristemo apical dormanteaislado simplásticamente. La pérdida de dormancia se asociacon la conexión simplástica del meristemo del brote con la redde floema del tubérculo, y con una descarga simplástica en laregión de la yema, todo lo cual favorece el crecimiento activode los nuevos brotes.

Cape gooseberry fruits at the maturity stages 3 (yellow greenish) or 5 (yellow orange) and with calyx drying for 6 hours at 18 or 24ºC, were stored at the temperature of 18ºC and 85 % relative humidity for 20 days, to evaluate physical-chemical and physiological changes. The cape gooseberry, a climacteric fruit, presented the maximum of respiration between 6 and 8 days of storage. The 6th day of storage seems to be crucial due to the very high metabolism and the maximum contents of sugars and acids on this day. Soluble solids tended to increase and the titratable acids went to diminish. The fruit's sugar content was characterized by a major concentration of sucrose, followed by glucose and fructose. While the citric acid showed its highest level at the sixth storage day that of the tartaric acid increased constantly up to 18 days. The fruit maturity stage 3 is that which best conserved the sugars and organic acids evaluated. The maturity index influenced more than calyx drying the postharvest behavior of cape gooseberry. Calyx drying at 24ºC caused the highest climacteric peak and originated the highest loss of fresh weight in fruits harvested at maturity index 5. Key words: Physalis peruviana; respiration; climacteric fruit; Brix degrees; organic acids; sugars. Frutos de uchuva en estados de madurez 3 (amarillo verdoso) ó 5 (amarillo naranja) y con secado del cáliz durante seis horas a 18 y 24ºC, se almacenaron a temperatura ambiente (18ºC) y humedad relativa del 75% durante 20 días, con el fin de evaluar cambios físico-químicos y fisiológicos. La uchuva, fruto climatérico, presentó el máximo de respiración entre los 6 y 8 días de almacenamiento. El día 6 de almacenamiento parece ser crucial debido al metabolismo muy elevado y los contenidos más altos de azúcares y ácidos. Los sólidos solubles totales tendieron a aumentar, la acidez titulable a disminuir. El contenido de azúcares se caracterizó por mayor concentración de sacarosa, seguido por glucosa y fructosa. Mientras el ácido cítrico mostró el nivel más alto a los 6 días de almacenamiento, el del ácido tartárico aumentó constantemente hasta los 18 días. El estado de madurez 3 del fruto conservó mejor los azúcares y ácidos orgánicos. El índice de madurez influyó más que el secado del cáliz, sobre el comportamiento poscosecha de la uchuva. El secado del cáliz a 24ºC causó el pico climatérico más alto, originó la mayor pérdida de peso fresco en frutos cosechados al índice de madurez 5. Palabras claves: Physalis peruviana; respiración; fruto climatérico; grados Brix; ácidos orgánicos; azúcares.

INTRODUÇÃO: Fibrilação atrial tem sido tratada pelo procedimento do Labirinto (Cox) e suas modificações. Há, no entanto, evidências de que o isolamento dos óstios das veias pulmonares ou exclusão do átrio esquerdo poderia ser eficaz para este fim. CASUÍSTICA E MÉTODOS: Avaliamos os resultados iniciais da técnica simplificada de isolamento cirúrgico dos óstios das veias pulmonares para tratar fibrilação atrial crônica em pacientes operados por lesão valvar mitral. Foram tratados 7 pacientes por esta técnica (grupo IVP) e comparados com série prévia de 57 casos submetidos a cirurgia do Labirinto (Cox 3). RESULTADOS: A idade média foi de 49±8 anos vs 49±11 anos, (IVP vs. Cox3), sendo 71% e 72% (IVP vs. Cox 3) do sexo feminino. Dimensões do átrio esquerdo 5,5±0,7 cm vs. 6,0±1,1 cm (IVP vs. Cox 3). Fração de ejeção ventricular 63±10% vs. 64±6% (IVP vs. Cox 3). Tempo CEC 91±33 min vs. 104±29 min (IVP vs. Cox 3). Tempo de isquemia71±23 min vs. 83±26 min (IVP vs. Cox 3). Ritmo pós-operátório sinusal/atrial n(%): 6(86) vs. 46(80) (IVP vs. Cox 3). Ritmo marcapasso n(%):1 (14) vs. 4 (7) (IVP vs. Cox 3). Fibrilação atrial n(%): 0 vs. 7 (13) (IVP vs. Cox 3). CONCLUSÕES: Resultados iniciais mostram reversão a ritmo sinusal na maioria dos casos em ambos procedimentos e manutenção do ritmo a longo prazo. Foi iniciado estudo prospectivo randomizado para avaliar o IVP comparativamente ao procedimento Cox 3.

We examined a possible protective effect of the nonpeptidyl low molecular weight radical scavenger IAC [bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decanedioate di-hydrochloride] on isolated human islet cells against isolation and culture oxidative stress. Islets isolated from pancreases of nondiabetic multiorgan donors by collagenase digestion were purified by density gradient centrifugation. After the isolation, islets were either exposed or not exposed for 7 days to 10 μmol/L IAC. We found that IAC markedly reduced oxidative stress and ameliorated islets function. These results suggest that the use of IAC could be an interesting pharmacological approach for the treatment of the islets before transplantation.

Abstract Background Natural product-likeness of a molecule, i.e. similarity of this molecule to the structure space covered by natural products, is a useful criterion in screening compound libraries and in designing new lead compounds. A closed source implementation of a natural product-likeness score, that finds its application in virtual screening, library design and compound selection, has been previously reported by one of us. In this note, we report an open-source and open-data re-implementation of this scoring system, illustrate its efficiency in ranking small molecules for natural product likeness and discuss its potential applications. Results The Natural-Product-Likeness scoring system is implemented as Taverna 2.2 workflows, and is available under Creative Commons Attribution-Share Alike 3.0 Unported License at http://www.myexperiment.org/packs/183.html. It is also available for download as executable standalone java package from http://sourceforge.net/projects/np-likeness/under Academic Free License. Conclusions Our open-source, open-data Natural-Product-Likeness scoring system can be used as a filter for metabolites in Computer Assisted Structure Elucidation or to select natural-product-like molecules from molecular libraries for the use as leads in drug discovery.

Abstract Background Persons with schizophrenia and related disorders may be particularly sensitive to a number of determinants of service use, including those related with illness, socio-demographic characteristics and organizational factors. The objective of this study is to identify factors associated with outpatient contacts at community mental health services of patients with schizophrenia or related disorders. Methods This cross-sectional study analyzed 1097 patients. The main outcome measure was the total number of outpatient consultations during one year. Independent variables were related to socio-demographic, clinical and use of service factors. Data were collected from clinical records. Results The multilevel linear regression model explained 46.35% of the variance. Patients with significantly more contacts with ambulatory services were not working and were receiving welfare benefits (p = 0.02), had no formal education (p = 0.02), had a global level of severity of two or three (four being the most severe) (p < 0.001), with one or more inpatient admissions (p < 0.001), and in contact with both types of professional (nurses and psychiatrists) (p < 0.001). The patients with the fewest ambulatory contacts were those with diagnoses of persistent delusional disorders (p = 0.04) and those who were attended by four of the 13 psychiatrists (p < 0.001). Conclusions As expected, the variables that explained the use of community service could be viewed as proxies for severity of illness. The most surprising finding, however, was that a group of four psychiatrists was also independently associated with use of ambulatory services by patients with schizophrenia or related disorders. More research is needed to carefully examine how professional support networks interact to affect use of mental health.

Abstract Background Morphogenetic events that shape the Drosophila melanogaster embryo are tightly controlled by a genetic program in which specific sets of genes are up-regulated. We used a suppressive subtractive hybridization procedure to identify a group of developmentally regulated genes during early stages of D. melanogaster embryogenesis. We studied the spatiotemporal activity of these genes in five different intervals covering 12 stages of embryogenesis. Results Microarrays were constructed to confirm induction of expression and to determine the temporal profile of isolated subtracted cDNAs during embryo development. We identified a set of 118 genes whose expression levels increased significantly in at least one developmental interval compared with a reference interval. Of these genes, 53% had a phenotype and/or molecular function reported in the literature, whereas 47% were essentially uncharacterized. Clustering analysis revealed demarcated transcript groups with maximum gene activity at distinct developmental intervals. In situ hybridization assays were carried out on 23 uncharacterized genes, 15 of which proved to have spatiotemporally restricted expression patterns. Among these 15 uncharacterized genes, 13 were found to encode putative secreted and transmembrane proteins. For three of them we validated our protein sequence predictions by expressing their cDNAs in Drosophila S2R+ cells and analyzed the subcellular distribution of recombinant proteins. We then focused on the functional characterization of the gene CG6234. Inhibition of CG6234 by RNA interference resulted in morphological defects in embryos, suggesting the involvement of this gene in germ band retraction. Conclusion Our data have yielded a list of developmentally regulated D. melanogaster genes and their expression profiles during embryogenesis and provide new information on the spatiotemporal expression patterns of several uncharacterized genes. In particular, we recovered a substantial number of unknown genes encoding putative secreted and transmembrane proteins, suggesting new components of signaling pathways that might be incorporated within the existing regulatory networks controlling D. melanogaster embryogenesis. These genes are also good candidates for additional targeted functional analyses similar to those we conducted for CG6234. See related minireview by Vichas and Zallen: http://www.jbiol.com/content/8/8/76

Introduction and Importance: BIA-ALCL is a non-Hodgkin lymphoma occurring primarily in women with textured breast implants, typically presenting as late seroma. Diagnosis involves ultrasound-guided fine-needle aspiration or core needle biopsy, followed by cytologic and immunohistochemical evaluation. Positive results show CD30 cell expression and lack ALK expression. Treatment includes removing breast implants and the periprosthetic capsule. If the lymphoma has spread, en bloc capsulectomy, immunotherapy, and chemotherapy are required. Reconstruction can be done with smooth implants or autologous tissue., Presentation of Case: We present here the case of a woman with a 12-year history of microtextured breast implants, without any cancer family background, who presented with peri-implant effusion in the left breast, which tested positive for BIA-ALCL at stage IA. The patient underwent breast implant removal with total capsulectomy and posterior successful autologous tissue reconstruction, demonstrating that outcomes can be satisfactory when properly treated., Clinical Discussion: Paying attention to signs in women with breast implants, beyond imaging tests, can aid in the early diagnosis of BIA-ALCL and ensure a not aggressive treatment. This approach allows the reconstruction with autologous tissue without the need of further implants., Conclusion: BIA-ALCL is a rare disease, further studies about this lymphoma can help with early diagnosis and potential prevention., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many cancers remain resistant. Tumors deemed "cold" based on lack of T cell infiltration show reduced potential for CPI therapy. Cancer vaccines may overcome the inadequacy of existing T cells by inducing the needed antitumor T cell response to synergize with CPIs and overcome resistance., Methods: CT26 and TC1 tumor cells were injected subcutaneously into mice. Mice were treated with combinations of CPIs alone or a cancer vaccine specific to the tumor antigen E7 present in TC1 cells. CPIs for the TC1 model were selected because of immunophenotyping TC1 tumors. Antitumor and protumor immunity, tumor size and survival, sequence and timing of vaccine and CPI administration, and efficacy of treatment in young and aged mice were probed., Results: While "hot" CT26 tumors are treatable with combinations of second-generation CPIs alone or with anti-TGFβ, "cold" TC1 tumor reduction requires the synergy of a tumor-antigen-specific vaccine in combination with two CPIs, anti-TIGIT and anti-PD-L1, predicted by tumor microenvironment (TME) characterization. The synergistic triple combination delays tumor growth better than any pairwise combination and improves survival in a CD8+T cell-dependent manner. Depletion of CD4+T cells improved the treatment response, and depleting regulatory T cells (Treg) revealed Tregs to be inhibiting the response as also predicted from TME analysis. We found the sequence of CPI and vaccine administration dictates the success of the treatment, and the triple combination administered concurrently induces the highest E7-specific T cell response. Contrary to young mice, in aged mice, the cancer vaccine alone is ineffective, requiring the CPIs to delay tumor growth., Conclusions: These findings show how pre-existing or vaccine-mediated de novo T cell responses can both be amplified by and facilitate synergistic CPIs and Treg depletion that together lead to greater survival, and how analysis of the TME can help rationally design combination therapies and precision medicine to enhance clinical response to CPI and cancer vaccine therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The European Platform on Rare Disease Registration (EU RD Platform) aims to address the fragmentation of European rare disease (RD) patient data, scattered among hundreds of independent and non-coordinating registries, by establishing standards for integration and interoperability. The first practical output of this effort was a set of 16 Common Data Elements (CDEs) that should be implemented by all RD registries. Interoperability, however, requires decisions beyond data elements - including data models, formats, and semantics. Within the European Joint Programme on Rare Diseases (EJP RD), we aim to further the goals of the EU RD Platform by generating reusable RD semantic model templates that follow the FAIR Data Principles., Results: Through a team-based iterative approach, we created semantically grounded models to represent each of the CDEs, using the SemanticScience Integrated Ontology as the core framework for representing the entities and their relationships. Within that framework, we mapped the concepts represented in the CDEs, and their possible values, into domain ontologies such as the Orphanet Rare Disease Ontology, Human Phenotype Ontology and National Cancer Institute Thesaurus. Finally, we created an exemplar, reusable ETL pipeline that we will be deploying over these non-coordinating data repositories to assist them in creating model-compliant FAIR data without requiring site-specific coding nor expertise in Linked Data or FAIR., Conclusions: Within the EJP RD project, we determined that creating reusable, expert-designed templates reduced or eliminated the requirement for our participating biomedical domain experts and rare disease data hosts to understand OWL semantics. This enabled them to publish highly expressive FAIR data using tools and approaches that were already familiar to them., (© 2022. The Author(s).)

During the lowering phase of a squat, it has been observed that a posterior pelvic tilt (PPT) may occur when squatting to full depth. Research suggests that defaulting to compensatory movement strategies, such as PPT, during the squat may correlate with risk of lower extremity and trunk pathology. The purpose of this study was to examine hip flexion (HF) angles at the point when PPT occurs among three conditions: standard squats, heel raise squats, and supine passive HF; analyzing the differences in depth between standard and heel raise squats; and calculating differences in knee angles and ankle excursion between standard and heel raise squats. 28 participants performed bodyweight squats and underwent supine passive HF while outfitted with 32 retroreflective motion capture markers. Hip, knee, and ankle joint angles were extracted at the point of PPT. A one-way repeated measures ANOVA was used to determine differences in hip joint angles between conditions, and a paired sample t-test was used to compare knee angles, ankle excursion, and squat depth between standard and heel raise squats. HF angles at PPT remained unchanged across all conditions. However, significantly greater knee flexion, ankle excursion, and squat depth were observed in the heel raise squats compared to the standard squats. Results suggest that PPT is a compensatory movement that occurs as the femur compresses into the acetabulum once hip flexion has been exhausted.

Breast cancer is the leading cause of death by cancer among women in less developed regions. In Colombia, few published studies have applied next-generation sequencing technologies to evaluate the genetic factors related to breast cancer. This study characterized the exome of three patients with breast cancer from southwestern Colombia to identify likely pathogenic or disease-related DNA sequence variants in tumor cells. For this, the exomes of three tumor tissue samples from patients with breast cancer were sequenced. The bioinformatics analysis identified two pathogenic variants in Fgfr4 and Nf1 genes, which are highly relevant for this type of cancer. Specifically, variant FGFR4-c.1162G>A predisposes individuals to a significantly accelerated progression of this pathology, while NF1-c.1915C>T negatively alters the encoded protein and should be further investigated to clarify the role of this variant in this neoplasia. Moreover, 27 novel likely pathogenic variants were found and 10 genes showed alterations of pathological interest. These results suggest that the novel variants reported here should be further studied to elucidate their role in breast cancer.

Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.

Background: Notwithstanding the significant advances in automated imaging techniques in the past 2 decades, subjective evaluation of the optic disc still remains an important part of glaucoma propaedeutic. In places with limited resources and a high demand for ophthalmic care, anatomical evaluation of glaucoma cases often relies solely on slit-lamp-based fundus biomicroscopic examination, which is frequently performed without mydriasis., Objective: The aim of this study was to compare metrics related to fundus biomicroscopy examination of the optic nerve head and peripapillary retinal nerve fiber layer (pRNFL) with and without mydriasis., Material and Methods: Healthy individuals, patients with early glaucoma, and glaucoma suspects were prospectively enrolled. Patients were examined before and after mydriasis by three glaucoma specialists, who estimated patients' vertical cup-to-disc ratio (CDR) and evaluated the presence of glaucomatous signs: laminar dot sign, disc hemorrhage, disc saucering, disc notching, peripapillary atrophy, localized pRNFL defect, and loss of the ISNT pattern. Main outcome measures were the intra-observer comparison, the inter-observer agreement, and the abilities to identify glaucomatous signs before and after mydriasis., Results: Thirty patients (60 eyes) were enrolled (mean age, 62.3 ± 11.6 years). Considering the evaluation of the three examiners, the mean vertical CDR increased from 0.41 to 0.44 (p = 0.02), and the median of the coefficient of variation of the measures was reduced from 0.24 to 0.11 (p = 0.01) after mydriasis. Regarding the inter-observer agreement evaluation, the kappa coefficient values ranged from 0.64 to 0.72 before mydriasis and from 0.71 to 0.77 after mydriasis. Dot sign and disc notching were better identified through fundoscopic examination with mydriasis compared to the nonmydriatic examination (p < 0.01)., Conclusion: Our results suggest that fundus biomicroscopy should be performed with mydriasis whenever possible, as it yells a better intra- and inter-observer agreement and improves the detection of glaucomatous signs. Moreover, examiners seem to underestimate CDR values without mydriasis. Further investigation is warranted to validate these findings by general ophthalmologists and in different populations., (© 2019 S. Karger AG, Basel.)

Background: Repetitive DNA sequences (Repeats) are significant regions in the human genome that have a specific genomic distribution, structure, and several binding sites for genome architecture and function. In consequence, the possible configurations of Repeats in specific and dynamic regions like the gene promoters could define footprints for molecular mechanisms, pathways, and cell function beyond their density in the genome. Here we explored the distribution of Repeats in the upstream promoter region of the human coding genes with the aim to identify specific configurations, clusters and functional meaning of those elements. Our method includes structural descriptions, hierarchical clustering, pathway association, and functional enrichment analysis., Results: We report here several configurations of Repeats in the upstream promoter region (UPR), which define 2729 patterns for the 80% of the human coding genes. There are 47 types of Repeats in these configurations, where the most frequent were Alu, Low&#95;complexity, MIR, Simple&#95;repeat, LINE/L2, LINE/L1, hAT-Charlie, and ERV1. The distribution, length, and the high frequency of Repeats in the UPR defines several patterns and clusters, where the minimum frequency of configuration among Repeats was higher than 0.7. We found those clusters associated with cellular pathways and ontologies; thus, it was plausible to determine groups of Repeats to specific functional insights, for example, pathways for Genetic Information Processing or Metabolism shows particular groups of Repeats with specific configurations., Conclusion: Based on these findings, we propose that specific configurations of repetitive elements describe frequent patterns in the upstream promoter for sets of human coding genes, which those correlated to specific and essential cell pathways and functions.

The multifractal analysis has allowed to quantify the genetic variability and non-linear stability along the human genome sequence. It has some implications in explaining several genetic diseases given by some chromosome abnormalities, among other genetic particularities. The multifractal analysis of a genome is carried out by dividing the complete DNA sequence in smaller fragments and calculating the generalized dimension spectrum of each fragment using the chaos game representation and the box-counting method. This is a time consuming process because it involves the processing of large data sets using floating-point representation. In order to reduce the computation time, we designed an application-specific processor, here called multifractal processor, which is based on our proposed hardware-oriented algorithm for calculating efficiently the generalized dimension spectrum of DNA sequences. The multifractal processor was implemented on a low-cost SoC-FPGA and was verified by processing a complete human genome. The execution time and numeric results of the Multifractal processor were compared with the results obtained from the software implementation executed in a 20-core workstation, achieving a speed up of 2.6x and an average error of 0.0003 percent.

Background: Short linear motifs in host organisms proteins can be mimicked by viruses to create protein-protein interactions that disable or control metabolic pathways. Given that viral linear motif instances of host motif regular expressions can be found by chance, it is necessary to develop filtering methods of functional linear motifs. We conduct a systematic comparison of linear motifs filtering methods to develop a computational approach for predicting motif-mediated protein-protein interactions between human and the human immunodeficiency virus 1 (HIV-1)., Results: We implemented three filtering methods to obtain linear motif sets: 1) conserved in viral proteins (C), 2) located in disordered regions (D) and 3) rare or scarce in a set of randomized viral sequences (R). The sets C,D,R are united and intersected. The resulting sets are compared by the number of protein-protein interactions correctly inferred with them - with experimental validation. The comparison is done with HIV-1 sequences and interactions from the National Institute of Allergy and Infectious Diseases (NIAID). The number of correctly inferred interactions allows to rank the interactions by the sets used to deduce them: D∪R and C. The ordering of the sets is descending on the probability of capturing functional interactions. With respect to HIV-1, the sets C∪R, D∪R, C∪D∪R infer all known interactions between HIV1 and human proteins mediated by linear motifs. We found that the majority of conserved linear motifs in the virus are located in disordered regions., Conclusion: We have developed a method for predicting protein-protein interactions mediated by linear motifs between HIV-1 and human proteins. The method only use protein sequences as inputs. We can extend the software developed to any other eukaryotic virus and host in order to find and rank candidate interactions. In future works we will use it to explore possible viral attack mechanisms based on linear motif mimicry.

Purpose: The aim of the study was to compare the diagnostic ability of macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thickness in high-tension glaucoma (HTG) and low-tension glaucoma (LTG)., Patients and Methods: Glaucoma was defined as glaucomatous optic neuropathy and reproducible visual field defects. Patients were classified as having LTG if untreated intraocular pressure was ≤21 mm Hg on 2 different occasions. Only eyes with early glaucoma (mean deviation <-6 dB) were included. All patients underwent spectral-domain optical coherence tomography (SDOCT) imaging., Results: A total of 56 normal subjects, 64 HTG patients, and 35 LTG patients were enrolled. Overall, after adjusting for mean deviation and age, the average pRNFL thickness in eyes with LTG was 18.7 µm thinner than in eyes with HTG (17% difference, P<0.01). In the HTG group, no significant difference was found between areas under the receiver operating characteristic curve (AUCs) for average GCC and average pRNFL thicknesses (0.77 vs. 0.68, P=0.06). In the LTG group, average pRNFL thickness had a significantly larger AUC compared with average GCC thickness (0.95 vs. 0.81, P<0.001). Comparing AUCs between HTG and LTG groups, although the average GCC had similar AUCs in both groups (P=0.47), the average pRNFL thickness had a significantly larger AUC in the LTG group (P<0.001)., Conclusions: In eyes with early glaucoma, the pRNFL thickness scan seems to be a more accurate SDOCT protocol to identify those with LTG compared with the GCC thickness scan.

In order to obtain microalgal saponifiable lipids (SLs) fractions containing different polar lipid (glycolipids and phospholipids) contents, SLs were extracted from wet Nannochloropsis gaditana microalgal biomass using seven extraction systems, and the polar lipid contents of some fractions were reduced by low temperature acetone crystallization. We observed that the polar lipid content in the extracted lipids depended on the polarity of the first solvent used in the extraction system. Lipid fractions with polar lipid contents between 75.1% and 15.3% were obtained. Some of these fractions were transformed into fatty acid methyl esters (FAMEs, biodiesel) by methanolysis, catalyzed by the lipases Novozym 435 and Rhizopus oryzae in tert-butanol medium. We observed that the reaction velocity was higher the lower the polar lipid content, and that the final FAME conversions achieved after using the same lipase batch to catalyze consecutive reactions decreased in relation to an increase in the polar lipid content., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study was conducted to assess the clinical effect of photodynamic therapy (PDT) in the decontamination of the deep dentin of deciduous molars submitted to partial removal of carious tissue. After cavity preparation, dentin samples were taken from the pulp wall of nineteen deciduous molars before and after PDT application. Remaining dentin was treated with 0.01% methylene blue dye followed by irradiation with an InGaAlP diode laser (λ - 660 nm; 40 mW; 120 J/cm2; 120 s). Dentin samples were microbiologically assessed for the enumeration of total microorganisms, Lactobacillus spp. and mutans streptococci. There was no significant difference in the number of colony-forming units (CFU) for any of the microorganisms assessed (p > 0.05). Photodynamic therapy, using 0.01% methylene blue dye at a dosimetry of 120 J/cm2 would not be a viable clinical alternative to reduce bacterial contamination in deep dentin.

Biodiesel (fatty acid methyl esters, FAMEs) was produced from saponifiable lipids (SLs) extracted from wet Nannochloropsis gaditana biomass using methanolysis catalyzed by Rhizopus oryzae intracellular lipase. SLs were firstly extracted with ethanol to obtain 31 wt% pure SLs. But this low SL purity also gave a low biodiesel conversion (58%). This conversion increased up to 80% using SLs purified by crystallization in acetone (95 wt% purity). Polar lipids play an important role in decreasing the reaction velocity - using SLs extracted with hexane, which have lower polar lipid content (37.4% versus 49.0% using ethanol), we obtained higher reaction velocities and less FAME conversion decrease when the same lipase batch was reused. 83% of SLs were transformed to biodiesel using a 70 wt% lipase/SL ratio, 11:1 methanol/SL molar ratio, 10 mL t-butanol/g SLs after 72 h. The FAME conversion decreased to 71% after catalyzing three reactions with the same lipase batch., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The aim of this work was to obtain biodiesel (methyl esters) from the saponifiable lipids (SLs) fraction of the microalga Nannochloropsis gaditana, whose biomass dry weight contains 12.1 wt% of these lipids. SLs were extracted from the microalga as free fatty acids (FFAs) for subsequent transformation to methyl esters (biodiesel) by enzymatic esterification. Extraction as FFAs rather than as SLs allows them to be obtained with higher purity. Microalgal FFAs were obtained by direct saponification of lipids in the biomass and subsequent extraction-purification with hexane. Esterification of FFAs with methanol was catalysed by lipase Novozym 435 from Candida antarctica. Stability studies of this lipase in the operational conditions showed that the esterification degree (ED) attained with the same batch of lipase remained constant over six reaction cycles (36 h total reaction time). The optimal conditions attained for 4 g of FFAs were 25°C, 200 rpm, methanol/FFA molar ratio of 1.5:1, Novozym 435/FFA ratio of 0.025:1 w/w and 4 h reaction time. In these conditions the ED attained was 92.6%, producing a biodiesel with 83 wt% purity from microalgal FFAs. Several experimental scales were tested (from 4 to 40 g FFAs), and in all cases similar EDs were obtained., (Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

The progressive ageing of population has turned the mild cognitive impairment (MCI) into a prevalent disease suffered by elderly. Consequently, the spatial disorientation has become a significant problem for older people and their caregivers. The ambient-assisted living applications are offering location-based services for empowering elderly to go outside and encouraging a greater independence. Therefore, this paper describes the design and technical evaluation of a location-awareness service enabler aimed at supporting and managing probable wandering situations of a person with MCI. Through the presence capabilities of the IP multimedia subsystem (IMS) architecture, the service will alert patient's contacts if a hazardous situation is detected depending on his location. Furthermore, information about the older person's security areas has been included in the user profile managed by IMS. In doing so, the service enabler introduced contribute to "context-awareness" paradigm allowing the adaptation and personalization of services depending on user's context and specific conditions or preferences.

Fatty acid methyl esters (FAMEs, biodiesel) were produced from Nannochloropsis gaditana wet biomass (12% saponifiable lipids, SLs) by extraction of SLs and lipase catalyzed transesterification. Lipids were extracted by ethanol (96%)-hexane, and 31% pure SLs were obtained with 85% yield. When the lipids were degummed, SL purity increased to 95%. Novozym 435 was selected from four lipases tested. Both the lipidic composition and the use of t-butanol instead of hexane increased the reaction velocity and the conversion, since both decreased due to the adsorption of polar lipids on the lipase immobilization support. The best FAME yield (94.7%) was attained at a reaction time of 48h and using 10mL of t-butanol/g SL, 0.225gN435/g SL, 11:1 methanol/SL molar ratio and adding the methanol in three steps. In these conditions the FAME conversion decreased by 9.8% after three reaction cycles catalyzed by the same lipase batch., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the context of the long-term care for older adults, informal carers play a key role. Daily competing priorities or a care-skills deficit may lead them to stress, anxiety and/or depression. The iCarer project (AAL-2012-5-239) proposes the design and implementation of a cloud-inspired personalised and adaptive platform which will offer support to informal carers of older adults with cognitive impairment. By means of a holistic approach comprising technologies and services addressing the intelligent and interactive monitoring of activities, knowledge management for personalised guidance and orientation, virtual interaction, e-learning, care coordination facilities and social network services, iCarer aims to reduce the informal carer stress and to enhance the quality of care they provide, thus improving their quality of life. The iCarer platform will be evaluated through a multi-centre non-controlled study (4 months; 48 homes located in England and in Slovenia). Currently the iCarer project is completing the development work. The evaluation trial is expected to start in August 2015.

Saponifiable lipids (SLs) were extracted with hexane from wet biomass (86 wt% water) of the microalga Nannochloropsis gaditana in order to transform them into fatty acid methyl esters (FAMEs, biodiesel). The influence of homogenization pressure on SL extraction yield at low temperature (20-22 °C) was studied. Homogenization at 1700 bar tripled the SL extraction yield. Two biomass batches with similar total lipid content but different lipidic compositions were used. Batch 1 contained fewer SLs (12.0 wt%) and neutral saponifiable lipids (NSLs, 7.9 wt%) than batch 2 (21.6 and 17.2 wt%, respectively). For this reason, and due to the selectivity of hexane toward NSLs, high SL yield (69.1 wt%) and purity (71.0 wt%) were obtained from batch 2. Moreover, this extract contains a small percentage of polyunsaturated fatty acids (16.9 wt%), thereby improving the biodiesel quality. Finally, up to 97.0% of extracted SLs were transformed to FAMEs by acid catalyzed transesterification., (Copyright © 2014 Elsevier Ltd. All rights reserved.)