Deep learning classification of lipid droplets in quantitative phase images.

We report the application of supervised machine learning to the automated classification of lipid droplets in label-free, quantitative-phase images. By comparing various machine learning methods commonly used in biomedical imaging and remote sensing, we found convolutional neural networks to outperform others, both quantitatively and qualitatively. We describe our imaging approach, all implemented machine learning methods, and their performance with respect to computational efficiency, required training resources, and relative method performance measured across multiple metrics. Overall, our results indicate that quantitative-phase imaging coupled to machine learning enables accurate lipid droplet classification in single living cells. As such, the present paradigm presents an excellent alternative of the more common fluorescent and Raman imaging modalities by enabling label-free, ultra-low phototoxicity, and deeper insight into the thermodynamics of metabolism of single cells.

Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation.

Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus-vacuole junction contact site. In search for factors determining identity of these LDs, we screened ∼6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.

Dapagliflozina: más allá del control glucémico en el tratamiento de la diabetes mellitus tipo 2 / Dapagliflozin: beyond glycemic control in the treatment of type 2 diabetes mellitus

Los pacientes con diabetes mellitus tipo 2 (DM2) tienen un alto o muy alto riesgo cardiovascular. Las guías de práctica clínica se centran en la necesidad de alcanzar un control glucémico óptimo, sin olvidar que las estrategias de abordaje terapéutico multifactorial han demostrado importantes beneficios cardiovasculares en estos pacientes. Los inhibidores del cotransportador sodio-glucosa 2 (SGLT-2) son un nuevo grupo de fármacos de administración por vía oral en el tratamiento de la DM2 que actúan inhibiendo la reabsorción de glucosa en el túbulo proximal renal con el consiguiente efecto glucosúrico y disminución de la glucemia plasmática. La dapagliflozina, inhibidor de SGLT-2 comercializado en Europa y Australia, ha demostrado conseguir reducciones de hemoglobina glucosilada similares a otros antidiabéticos orales, así como efectos beneficiosos en las principales comorbilidades asociadas a la DM2. Por ello, hemos considerado de interés revisar la eficacia clínica de este nuevo hipoglucemiante oral en el control glucémico y riesgo de hipoglicemias, así como su impacto en el peso corporal, la presión arterial, el perfil lipídico y la función renal

Patients with type 2 diabetes mellitus (T2DM) have a high or very high cardiovascular risk. The clinical practice guidelines focus on the need to achieve optimal glycemic control, and strategies for a multifactorial therapeutic approach have shown significant cardiovascular benefits in these patients. Inhibitors of sodium-glucose co-transporter 2 (SGLT-2) are a new class of orally administered drugs in the treatment of T2DM, which act by inhibiting reabsorption of glucose in the renal proximal tubule with consequent glycosuric effect and lowering of blood glucose. Dapagliflozin, SGLT-2 inhibitor marketed in Europe and Australia, has been shown to achieve glycosylated hemoglobin reductions similar to other oral agents, as well as beneficial effects on major comorbidities associated with T2DM. Therefore, it is considered of interest to review the clinical efficacy of this new oral hypoglycemic on glycemic control, risk of hypoglycemia, and its impact on body weight, blood pressure, lipid profile and renal function

Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.

O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões sólidas de ibuprofeno com cada um dos seguintes excipientes: álcool cetílico, ácido esteárico e óleo de rícino hidrogenado. Estas formulações tinham por finalidade melhorar as características físicas e mecânicas e prolongar a liberação deste fármaco. Foram, também, preparadas misturas físicas do ibuprofeno com os mesmos excipientes e nas mesmas proporções. As dispersões sólidas de ibuprofeno/ácido esteárico e as dispersões sólidas de ibuprofeno/óleo de rícino hidrogenado foram aquelas que apresentaram melhores características de escoamento comparativamente com o ibuprofeno puro. Por outro lado, foram preparadas cápsulas de gelatina com as diferentes micropartículas lipídicas e dispersões sólidas e submetidas a ensaios de dissolução com o objetivo de estudar a influência dos sistemas preparados nos perfis de liberação do ibuprofeno. A liberação prolongada do ibuprofeno foi conseguida nas diferentes micropartículas lipídicas e dispersões sólidas preparadas com os diferentes excipientes.