The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.

Mitochondrial biology has always been a relevant field in chronic diseases such as fibrosis or cancer in different organs of the human body, not to mention the strong association between mitochondrial dysfunction and aging. With the development of new technologies and the emergence of new methodologies in the last few years, the role of mitochondria in pulmonary chronic diseases such as idiopathic pulmonary fibrosis (IPF) has taken an important position in the field. With this review, we will highlight the latest advances in mitochondrial research on pulmonary fibrosis, focusing on the role of the mitochondria in the aging lung, new proposals for mechanisms that support mitochondrial dysfunction as an important cause for IPF, mitochondrial dysfunction in different cell populations of the lung, and new proposals for treatment of the disease.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

BACKGROUND/AIM: The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. MATERIALS AND METHODS: After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. RESULTS: The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). CONCLUSION: In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

Dragon's Blood Sap Microencapsulation within Whey Protein Concentrate and Zein Using Electrospraying Assisted by Pressurized Gas Technology.

Dragon's blood sap (DBS) obtained from the bark of Croton lechleri (Müll, Arg.) is a complex herbal remedy of pharmacological interest due to its high content in polyphenols, specifically proanthocyanidins. In this paper, electrospraying assisted by pressurized gas (EAPG) was first compared with freeze-drying to dry natural DBS. Secondly, EAPG was used for the first time to entrap natural DBS at room temperature into two different encapsulation matrices, i.e., whey protein concentrate (WPC) and zein (ZN), using different ratios of encapsulant material: bioactive compound, for instance 2:1 w/w and 1:1 w/w. The obtained particles were characterized in terms of morphology, total soluble polyphenolic content (TSP), antioxidant activity, and photo-oxidation stability during the 40 days of the experiment. Regarding the drying process, EAPG produced spherical particles with sizes of 11.38 ± 4.34 µm, whereas freeze-drying produced irregular particles with a broad particle size distribution. However, no significant differences were detected between DBS dried by EAPG or freeze-drying in TSP, antioxidant activity, and photo-oxidation stability, confirming that EAPG is a mild drying process suitable to dry sensitive bioactive compounds. Regarding the encapsulation process, the DBS encapsulated within the WPC produced smooth spherical microparticles, with average sizes of 11.28 ± 4.28 µm and 12.77 ± 4.54 µm for ratios 1:1 w/w and 2:1 w/w, respectively. The DBS was also encapsulated into ZN producing rough spherical microparticles, with average sizes of 6.37 ± 1.67 µm and 7.58 ± 2.54 µm for ratios 1:1 w/w and 2:1 w/w, respectively. The TSP was not affected during the encapsulation process. However, a slight reduction in antioxidant activity measured by DPPH was observed during encapsulation. An accelerated photo-oxidation test under ultraviolet light confirmed that the encapsulated DBS showed an increased oxidative stability in comparison with the non-encapsulated DBS, with the stability being enhanced for the ratio of 2:1 w/w. Among the encapsulating materials and according to the ATR-FTIR results, ZN showed increased protection against UV light. The obtained results demonstrate the potential of EAPG technology in the drying or encapsulation of sensitive natural bioactive compounds in a continuous process available at an industrial scale, which could be an alternative to freeze-drying.

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients.

COVID-19 and public transport: an overview and recommendations applicable to Latin America / COVID-19 y transporte público: una revisión y recomendaciones aplicables a América Latina

Abstract The article presents a general overview on COVID-19 transmission in the context of public transport, particularly applicable to decision making in Latin America. Based on recent findings on COVID-19 transmission and the relative importance of each factor (droplets, fomites, and aerosol routes) in such transmission, we seek to update the discussion on the topic that has generally been based on social distance as the only parameter for reducing the risk of transmission and broadens the vision to integrate ventilation, users' behavior (mask and eye protection use, silence while in the transport system) and travel distance. Recommendations to improve mobility conditions reducing the risk of COVID-19 contagion are provided.

Resumen El artículo presenta una revisión de transmisión de COVID-19 en el contexto de transporte público, con aplicación particular para toma de decisiones en América Latina. Con base en los hallazgos recientes sobre transmisión de Covid-19 y la importancia relativa de cada factor (gotículas, fómites y rutas de aerosoles) en dicha transmisión, buscamos actualizar la discusión sobre el tema que generalmente se ha basado en la "distancia social" como parámetro único de reducción de riesgo de transmisión y amplía esta visión para integrar la ventilación, el comportamiento de usuarios (uso de mascarilla, protección ocular, silencio), y la distancia de viaje. Se indican al final recomendaciones para mejorar las condiciones de movilidad en general sin aumentar el riesgo de contagio de Covid-19.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development.

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.

Room Temperature Nanoencapsulation of Bioactive Eicosapentaenoic Acid Rich Oil within Whey Protein Microparticles.

In this study, emulsion electrospraying assisted by pressurized gas (EAPG) has been performed for the first time to entrap ca. 760 nm droplets of the bioactive eicosapentaenoic acid (EPA)-rich oil into whey protein concentrate (WPC) at room temperature. The submicron droplets of EPA oil were encapsulated within WPC spherical microparticles, with sizes around 5 µm. The EPA oil did not oxidize in the course of the encapsulation performed at 25 °C and in the presence of air, as corroborated by the peroxide value measurements. Attenuated Total Reflection-Fourier Transform Infrared spectroscopy and oxygen consumption tests confirmed that the encapsulated EPA-rich oil showed increased oxidative stability in comparison with the free oil during an accelerated oxidation test under ultraviolet light. Moreover, the encapsulated EPA-rich oil showed increased thermal stability in comparison with the free oil, as measured by oxidative thermogravimetric analysis. The encapsulated EPA-rich oil showed a somewhat reduced organoleptic impact in contrast with the neat EPA oil using rehydrated powdered milk as a reference. Finally, the oxidative stability by thermogravimetric analysis and organoleptic impact of mixtures of EPA and docosahexaenoic acid (DHA)-loaded microparticles was also studied, suggesting an overall reduced organoleptic impact compared to pure EPA. The results here suggest that it is possible to encapsulate 80% polyunsaturated fatty acids (PUFAs)-enriched oils by emulsion EAPG technology at room temperature, which could be used to produce personalized nutraceuticals or pharmaceuticals alone or in combination with other microparticles encapsulating different PUFAs to obtain different targeted health and organoleptic benefits.

Refractory hypophosphatemia following ferric carboxymaltose administration.

Hypophosphatemia is a rare side effect of intravenous iron replacement. Urinary phosphate wasting due to increased FGF23 is the most likely mechanism. Here, we present a case of intractable hypophosphatemia in a 32-year-old female patient with history of ulcerative colitis (UC), who was primarily hospitalized due to UC flare-up. Her urinary fractional excretion of phosphate was inappropriately elevated at 70%. A careful history revealed that she had been treated with ferric carboxymaltose 2 weeks prior to hospitalization, leading to a diagnosis of iron-induced hypophosphatemia. She was treated with 5 weeks of intravenous sodium phosphate since she did not tolerate oral supplementation. In conclusion, clinicians should be aware of iron-induced hypophosphatemia and be cautious when prescribing intravenous iron.

Recovery of COVID-19 acute respiratory distress syndrome with tocilizumab: successful outcome in two critically ill patients.

Background: Severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 is a challenge for nowadays medical practice. Although there is no clarity in the principal mechanism of lung damage and ARDS development, it has been suggested that one of the main reasons of this pathology is the hyperactivation of the immune system, better known as cytokine storm syndrome. Tocilizumab has been proposed to treat COVID-19 severe cases associated to ARDS. Results & methodology: Here we present two successful cases of tocilizumab administration in two COVID-19 patients with prior administration of antiviral therapy (hydroxychloroquine, azithromycin, lopinavir and ritonavir) with adequate response and resolution of ARDS, septic shock and severe pneumonia within the first 72 h. Discussion & conclusion: This case supports the usage of tocilizumab as an effective therapy in COVID-19 associated cytokine storm syndrome. Further studies should be done in order to assess its effectiveness and security.

Dosimetric and Contrast Noise Ratio Comparison of Three Different Digital Imaging Technologies in Mammography.

PURPOSE: The purpose of the study was to compare the three most common technologies available in digital mammography based in the evaluation of average glandular dose and contrast noise ratio (CNR). METHOD: The average glandular dose was estimated with a direct digital detector (aSe) with a pixel size of 0.85 µm, a photon counter with a pixel size of 50 µm and a computerized radiography (CR) system. A semiconductor detector was used to measure the input kerma to the detector, and the average glandular dose was calculated from the conversion factors dependent on the anode filter combination, half value layer and breast glandularity. RESULTS: The average glandular dose obtained with polymethyl methacrylate and CNR of mean thickness 4.5 cm using direct digital equipment was 1.02 mGy and CNR = 7.4; using the photon counter it was 0.43 mGy and CNR = 4.7 in C100 mode, and 0.64 mGy and CNR = 5.7 in C120 mode; and using the photostimulable CR, the estimated value was 1.65 mGy and CNR = 5.1. CONCLUSIONS: The photon counter offers a lower average glandular dose than the other two devices with adequate image quality (CNR). The CR equipment offers a similar CNR value but delivers a higher dose than the new generations of available mammograms.

Automated vertebrae localization and identification by decision forests and image-based refinement on real-world CT data.

PURPOSE: Development of a fully automatic algorithm for the automatic localization and identification of vertebral bodies in computed tomography (CT). MATERIALS AND METHODS: This algorithm was developed using a dataset based on real-world data of 232 thoraco-abdominopelvic CT scans retrospectively collected. In order to achieve an accurate solution, a two-stage automated method was developed: decision forests for a rough prediction of vertebral bodies position, and morphological image processing techniques to refine the previous detection by locating the position of the spinal canal. RESULTS: The mean distance error between the predicted vertebrae centroid position and truth was 13.7 mm. The identification rate was 79.6% on the thoracic region and of 74.8% on the lumbar segment. CONCLUSION: The algorithm provides a new method to detect and identify vertebral bodies from arbitrary field-of-view body CT scans.

Sistemas de alerta temprana con enfoque participativo: un desafío para la gestión del riesgo en colombia / Early warning systems with a participative approach: a challenge for risk management in colombia

La mayor parte de la población colombiana está en condiciones de riesgo debido a factores hidroclimatológicos, fuertemente influenciados por la variabilidad (VC) y el cambio climático (CC). A esto se suma el aumento de la vulnerabilidad por la inadecuada planificación y ocupación del territorio, propia de países en desarrollo. En este sentido, los sistemas de alerta temprana (SAT) facilitan los procesos de adaptación y mitigación de impactos, por lo que se constituyen en uno de los ejes transversales de la gestión del riesgo. En este trabajo se presenta una reflexión de diversos enfoques y experiencias nacionales e internacionales en SAT. A partir de lo anterior, se identificó que muchos SAT no llegan a ser implementados; y una vez en funcionamiento, existe desequilibrio entre sus componentes. Por otro lado, no se ajustan a las necesidades de los territorios como consecuencia de la escasa participación comunitaria, tanto en la etapa de diseño como en la de operación. Por ello, se considera que para obtener resultados eficaces, que promuevan la construcción de resiliencia, son necesarios SAT con enfoque participativo, que fortalezcan las capacidades de las comunidades para enfrentar las condiciones de riesgo de su entorno.

Most of the Colombian population is facing risks due to hydroclimatological factors, strongly influenced by the climate variability (CV) and climate change (CC). Likewise, vulnerability is continuously increasing because of inadequate land planning and occupation, common in developing countries. Therefore, early warning systems (EWS) facilitate the processes of adaptation and mitigation of impacts, which is why they constitute one of the transverse axes in risk management. This study aimed to review approaches to and field experiences with EWS throughout the world, including Colombia. We identified that many EWS are unimplemented; and once in operation, there exists an imbalance among components. On the other hand, some EWS fail to meet the territory needs as a result of poor community participation, both at design and operation stages. Hence, a participative approach in EWS to tackling risks and building up the capacities of the communities should be promoted for obtaining effective results.

Development of imaging biomarkers and generation of big data.

Several image processing algorithms have emerged to cover unmet clinical needs but their application to radiological routine with a clear clinical impact is still not straightforward. Moving from local to big infrastructures, such as Medical Imaging Biobanks (millions of studies), or even more, Federations of Medical Imaging Biobanks (in some cases totaling to hundreds of millions of studies) require the integration of automated pipelines for fast analysis of pooled data to extract clinically relevant conclusions, not uniquely linked to medical imaging, but in combination to other information such as genetic profiling. A general strategy for the development of imaging biomarkers and their integration in the cloud for the quantitative management and exploitation in large databases is herein presented. The proposed platform has been successfully launched and is being validated nowadays among the early adopters' community of radiologists, clinicians, and medical imaging researchers.