Effects of a comprehensive structured patient education intervention on disease-related knowledge and behaviour change among people living with type 2 diabetes in the Philippines.

Introduction: Addressing the ongoing needs of individuals with diabetes, particularly in low- and middle-income countries like the Philippines, requires a focus on regular follow-ups with healthcare teams, adherence to healthy behaviors, and effective patient education to prevent long-term complications. The aim of this study was to ascertain the impact of a comprehensive educational program for those living with diabetes in the Philippines. Methods: In a prospective study, a convenience sample of patients living with diabetes attending a cardiac rehabilitation or an outpatient diabetes clinic in the Philippines received a 12-week education intervention. Participants completed surveys at pre- and post-intervention assessing disease-related knowledge, health literacy, dietary habits, and tobacco use. Physical activity was measured by steps taken per day using wearable devices and by self-report of minutes of moderate or vigorous-intensity exercise per week. Satisfaction with the educational materials was also evaluated by a survey composed of Likert-type scale and open-ended questions. Descriptive statistics, paired t-tests or chi-square were used for data analysis. Results: Overall, 184 individuals living with diabetes type 2 (mean age = 54.4 ± 12.4, 32% female) completed both assessments. There was significant improvement in disease-related knowledge (p < 0.001), daily steps measured by a wearable device and self-reported minutes of moderate/vigorous-intensity exercise (p < 0.001), and the number of fruit and vegetable servings consumed per day (p = 0.001). No significant changes were observed in health literacy levels. One participant stopped using tobacco at post-education. Educational materials were highly satisfactory to participants. Lack of time, family responsibilities, and poor internet access were the main barriers to learning reported by participants. Suggestions to improve the education provided included assessment of information needs at the start of the education, having short summaries about the topics, follow-ups post-intervention, and inviting family members to sessions. Discussion: Results of this study demonstrated the positive effects a comprehensive structured patient education intervention on disease-related knowledge and behaviour changes among people living with type 2 diabetes in the Philippines.

An Episode of "Third Person" Phenomenon Involving Somesthetic and Visual Hallucinations in a World-Class Extreme Altitude Climber.

Psychotic symptoms can occur at high altitude. However, most reports are in the mountaineering literature and lack a clear medical assessment and interpretation. Here we report an episode of isolated high-altitude psychosis. It consisted of a "third person" phenomenon involving 2 sensory modalities: somesthetic (felt presence) and visual (the light of 2 flashlights) hallucinations. This episode occurred in a highly experienced climber when he was at an altitude of approximately 7500 m while descending at dusk from the summit of Gasherbrum I (8068 m). The symptoms lasted approximately 3 h and had fully resolved on reaching high camp (7150 m). No other physical or mental symptoms were reported. In addition to hypoxia, a number of other risk factors could have contributed to the occurrence of psychosis in this climber. These included sleep deprivation, exhaustion, dehydration, electrolyte disturbance, reduced visibility, feeling of isolation, and perceived danger. The climber has participated in many extreme altitude expeditions, and neither before nor since this episode has the climber experienced psychotic symptoms.

α4-α5 Helices on Surface of KRAS Can Accommodate Small Compounds That Increase KRAS Signaling While Inducing CRC Cell Death.

KRAS is the most frequently mutated oncogene associated with the genesis and progress of pancreatic, lung and colorectal (CRC) tumors. KRAS has always been considered as a therapeutic target in cancer but until now only two compounds that inhibit one specific KRAS mutation have been approved for clinical use. In this work, by molecular dynamics and a docking process, we describe a new compound (P14B) that stably binds to a druggable pocket near the α4-α5 helices of the allosteric domain of KRAS. This region had previously been identified as the binding site for calmodulin (CaM). Using surface plasmon resonance and pulldown analyses, we prove that P14B binds directly to oncogenic KRAS thus competing with CaM. Interestingly, P14B favors oncogenic KRAS interaction with BRAF and phosphorylated C-RAF, and increases downstream Ras signaling in CRC cells expressing oncogenic KRAS. The viability of these cells, but not that of the normal cells, is impaired by P14B treatment. These data support the significance of the α4-α5 helices region of KRAS in the regulation of oncogenic KRAS signaling, and demonstrate that drugs interacting with this site may destine CRC cells to death by increasing oncogenic KRAS downstream signaling.

Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells.

Mutant p53 proteins result from missense mutations in the TP53 gene, the most mutated in human cancer, and have been described to contribute to cancer initiation and progression. Therapeutic strategies for targeting mutant p53 proteins in cancer cells are limited and have proved unsuitable for clinical application due to problems related to drug delivery and toxicity to healthy tissues. Therefore, the discovery of efficient and safe therapeutic strategies that specifically target mutant p53 remains challenging. In this study, we generated gold nanoparticles (AuNPs) chemically modified with low molecular branched polyethylenimine (bPEI) for the efficient delivery of gapmers targeting p53 mutant protein. The AuNPs formulation consists of a combination of polymeric mixed layer of polyethylene glycol (PEG) and PEI, and layer-by-layer assembly of bPEI through a sensitive linker. These nanoparticles can bind oligonucleotides through electrostatic interactions and release them in the presence of a reducing agent as glutathione. The nanostructures generated here provide a non-toxic and powerful system for the delivery of gapmers in cancer cells, which significantly downregulated mutant p53 proteins and altered molecular markers related to cell growth and apoptosis, thus overcoming chemoresistance to gemcitabine.

Albumin-Based Nanoparticles for the Delivery of Doxorubicin in Breast Cancer.

Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. However, limitations of GLU like toxicity and interaction with drugs force the need for alternative cross-linkers. In the present study, several cross-linking systems were evaluated for the preparation of Bovine Serum Albumin (BSA) nanoparticles (ABNs) encapsulating Doxorubicin (Dox). Based on the results obtained from morphological characterization, in vitro release, and therapeutic efficacy in cells, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)-modified ABNs (ABN-SPDP) was chosen. Since ABN-SPDP are formed with disulfide linkage, the drug release is facilitated under a highly reducing environment present in the tumor sites. The cytotoxicity studies of those ABN-SPDP were performed in three different breast cell lines, highlighting the mechanism of cell death. The Dox-encapsulated ABN-SPDP showed toxicity in both the breast cancer cells (MCF-7 and MDA-MB-231), but, remarkably, a negligible effect was observed in non-tumoral MCF-10A cells. In addition to the hydrophilic Dox, this system could be used as a carrier for hydrophobic drugs like SN38. The system could be employed for the preparation of nanoparticles based on human serum albumin (HSA), which further enhances the feasibility of this system for clinical use. Hence, the albumin nanoparticles developed herein present an excellent potential for delivering various drugs in cancer therapy.

A city of cities: Measuring how 15-minutes urban accessibility shapes human mobility in Barcelona.

As cities expand, human mobility has become a central focus of urban planning and policy making to make cities more inclusive and sustainable. Initiatives such as the "15-minutes city" have been put in place to shift the attention from monocentric city configurations to polycentric structures, increasing the availability and diversity of local urban amenities. Ultimately they expect to increase local walkability and increase mobility within residential areas. While we know how urban amenities influence human mobility at the city level, little is known about spatial variations in this relationship. Here, we use mobile phone, census, and volunteered geographical data to measure geographic variations in the relationship between origin-destination flows and local urban accessibility in Barcelona. Using a Negative Binomial Geographically Weighted Regression model, we show that, globally, people tend to visit neighborhoods with better access to education and retail. Locally, these and other features change in sign and magnitude through the different neighborhoods of the city in ways that are not explained by administrative boundaries, and that provide deeper insights regarding urban characteristics such as rental prices. In conclusion, our work suggests that the qualities of a 15-minutes city can be measured at scale, delivering actionable insights on the polycentric structure of cities, and how people use and access this structure.

Actinomicosis musculoesquelética por Actinomyces europaeus / Musculoskeletal actinomycosis caused by Actinomyces europaeus

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Toward understanding calmodulin plasticity by molecular dynamics.

Aim: Calmodulin interacts in many different ways with its ligands. We aim to shed light on its plasticity analyzing the changes followed by the linker region and the relative position of the lobes using conventional molecular dynamics, accelerated MD and scaled MD (sMD). Materials & methods: Three different structures of calmodulin are compared, obtaining a total of 2.5 µs of molecular dynamics, which have been analyzed using the principal component analysis and clustering methodologies. Results: sMD simulations reach conformations that conventional molecular dynamics is not able to, without compromising the stability of the protein. On the other hand, accelerated MD requires optimization of the setup parameters to be useful. Conclusion: sMD is useful to study flexible proteins, highlighting those factors that justify its promiscuity.

Modeling and subtleties of K-Ras and Calmodulin interaction.

K-Ras, one of the most common small GTPases of the cell, still presents many riddles, despite the intense efforts to unveil its mysteries. Such is the case of its interaction with Calmodulin, a small acidic protein known for its role as a calcium ion sensor. Although the interaction between these two proteins and its biological implications have been widely studied, a model of their interaction has not been performed. In the present work we analyse this intriguing interaction by computational means. To do so, both conventional molecular dynamics and scaled molecular dynamics have been used. Our simulations suggest a model in which Calmodulin would interact with both the hypervariable region and the globular domain of K-Ras, using a lobe to interact with each of them. According to the presented model, the interface of helixes α4 and α5 of the globular domain of K-Ras would be relevant for the interaction with a lobe of Calmodulin. These results were also obtained when bringing the proteins together in a step wise manner with the umbrella sampling methodology. The computational results have been validated using SPR to determine the relevance of certain residues. Our results demonstrate that, when mutating residues of the α4-α5 interface described to be relevant for the interaction with Calmodulin, the interaction of the globular domain of K-Ras with Calmodulin diminishes. However, it is to be considered that our simulations indicate that the bulk of the interaction would fall on the hypervariable region of K-Ras, as many more interactions are identified in said region. All in all our simulations present a suitable model in which K-Ras could interact with Calmodulin at membrane level using both its globular domain and its hypervariable region to stablish an interaction that leads to an altered signalling.

Uracil grafted imine-based covalent organic framework for nucleobase recognition.

An imine-based covalent organic framework (COF) decorated in its cavities with uracil groups has shown selective recognition towards adenine in water. These results show how the confinement of the base-pair inside the COF's pores allows a remarkable selective recognition in aqueous media.

Decreased waterborne pathogenic bacteria in an urban aquifer related to intense shallow geothermal exploitation.

The implications of intensive use of shallow geothermal energy resources in shallow urban aquifers are still not known for waterborne pathogens relevant to human health. Firstly, we hypothesized that waterborne enteric pathogens would be relatively increased in heated groundwater plumes. To prove this, microbiological sampling of 31 piezometers covering the domain of an urban groundwater body affected by microbiological contamination and energetically exploited by 70 groundwater heat pump systems was performed. Mean differences of pathogenic bacteria contents between impacted and non-impacted monitoring points were assessed with a two-tailed independent Student's t-test or Mann-Whitney U and correlation coefficients were also calculated. Surprisingly, the results obtained revealed a significant and generalized decrease in waterborne pathogen contents in thermally impacted piezometers compared to that of non-impacted piezometers. This decrease is hypothesized to be caused by a heat shock to bacteria within the heat exchangers. The statistically significant negative correlations obtained between waterborne pathogen counts and temperature could be explained by the spatial distribution of the bacteria, finding that bacteria start to recover with increasing distance from the injection point. Also, different behavior groups fitting exponential regression models were found for the bacteria species studied, justified by the different presence and influence of several aquifer parameters and major, minor and trace elements studied, as well as the coexistence with other bacteria species. The results obtained from this work reinforce the concept of shallow geothermal resources as a clean energy source, as they could also provide the basis to control the pathogenic bacteria contents in groundwater bodies.

Respirar en altitudes extremas - Proyectos científicos "EVEREST" (Segunda parte) / Breathing at extreme altitudes - Scientific projects "EVEREST" (Second part)

Escalar el punto más alto de la Tierra, el Mt. Everest (8.848 m), sin equipos de oxígeno conlleva una demanda fisiológica que está próxima a la máxima capacidad de tolerancia humana. Exponerse a altitudes extremas condiciona drásticamente la función pulmonar, el nivel de oxígeno y el rendimiento físico. Esta revisión reúne interesantes aspectos respiratorios, de gases sanguíneos y ejercicio aeróbico aportados por aquellos proyectos científicos que han llevado a cabo mediciones fisiológicas entre 8.000 m y 8.848 m, en altitud real o simulada, como las Operaciones "Everest I" (1946), "Everest II" (1985) y "Everest III-COMEX" (1997), y las Expediciones "AMREE" (1981), "British 40th Anniversary Everest" (1993) y "Caudwell Xtrem Everest" (2007). Estos fascinantes eventos de investigación, junto a otros destacados proyectos biomédicos realizados a más de 5.500 m, muy especialmente las Expediciones "Silver Hut" (1960-61), "Italiana all’Everest" (1973) y "British Everest Medical" (1994), incluyendo aquellas pioneras observaciones científicas llevadas a cabo en el s.XIX hasta los más recientes proyectos de investigación realizados, han sentado las bases del conocimiento sobre la tolerancia humana ante niveles de hipoxia hipobárica extrema, donde el pulmón y la cadena respiratoria adquieren un trascendente protagonismo requiriéndose de finos ajustes fisiológicos que garanticen la oxigenación celular. Asimismo, se exponen ciertos aspectos geofísicos, factores climáticos y otros condicionantes ambientales que limitan la viabilidad biológica y pueden afectar la salud respiratoria de los alpinistas situados en las cotas superiores de la troposfera a la latitud subtropical donde se encuentra ubicada dicha montaña. Actualmente cientos de alpinistas intentan alcanzar la cumbre del Mt. Everest todos los años, pero solo algunos consiguen su objetivo sin inhalar oxígeno suplementario, entre ellos algunos excepcionalmente dotados nativos Sherpa, protagonistas de insospechadas hazañas en la montaña más elevada de la superficie terrestre, cuya cima roza el límite fisiológico de supervivencia para el ser humano

Climbing to the highest height on Earth, the Mt. Everest (8.848 m), without supplementary oxygen equipment involves a physiological demand that is close to the maximum human tolerance. Exposures at extreme altitudes drastically conditions lung function, stores of oxygen and physical performance. This review brings interesting aspects about respiration, blood gases and aerobic exercise reported by those scientific projects that have carried out physiological measurements between 8,000 m and 8,848 m above sea level, under real or simulated altitude: the Operations "Everest I" (1946), "Everest II" (1985), "Everest III-COMEX" (1997), and the Expeditions "AMREE" (1981), "British 40th Anniversary Everest" (1993), and "Caudwell Xtrem Everest" (2007). These fascinating scientific research events, along with other outstanding biomedical expeditions performed above 5,500 m, like especially the "Silver Hut" (1960-61), "Italiana all’Everest" (1973), and "British Everest Medical" (1994), including those pioneer scientific reports made on the XIX century until the most recent research projects performed, have laid the foundations and knowledge on the human tolerance to such extreme levels of hypobaric hypoxia, where the lung, breathing and respiratory chain takes on a major role requiring fine physiological adjustments to ensure cellular oxygenation. Geophysical aspects, climatic factors and other environmental conditions that limit the biological viability and can affect the respiratory health of climbers on the upper troposphere zone at the subtropical latitude where that mountain is located are likewise reviewed and analyzed. Every year, hundreds of climbers try to reach the top of Mt. Everest, but only a few of them achieved their goal without inhaling supplemental oxygen, including some exceptionally gifted Sherpa natives, protagonist on unsuspected exploits in the highest mountain on terrestrial surface, whose summit touch the physiological limit of survival for the human being

Respirar en altitudes extremas. Proyectos científicos "EVEREST" (Primera parte) / Breathing at extreme altitudes. Scientific projects "EVEREST" (First part)

Escalar el punto más alto de la Tierra, el Mt. Everest (8.848 m), sin equipos de oxígeno conlleva una demanda fisiológica que está próxima a la máxima capacidad de tolerancia humana. Exponerse a altitudes extremas condiciona drásticamente la función pulmonar, el nivel de oxígeno y el rendimiento físico. Esta revisión reúne interesantes aspectos respiratorios, de gases sanguíneos y ejercicio aeróbico aportados por aquellos proyectos científicos que han llevado a cabo mediciones fisiológicas entre 8.000 m y 8.848 m, en altitud real o simulada, como las Operaciones "Everest I" (1946), "Everest II" (1985) y "Everest III-COMEX" (1997), y las Expediciones "AMREE" (1981), "British 40th Anniversary Everest" (1993) y "Caudwell Xtrem Everest" (2007). Estos fascinantes eventos de investigación, junto a otros destacados proyectos biomédicos realizados a más de 5.500 m, muy especialmente las Expediciones "Silver Hut" (1960-61), "Italiana all'Everest" (1973) y "British Everest Medical" (1994), incluyendo aquellas pioneras observaciones científicas llevadas a cabo en el s.XIX hasta los más recientes proyectos de investigación realizados, han sentado las bases del conocimiento sobre la tolerancia humana ante niveles de hipoxia hipobárica extrema, donde el pulmón y la cadena respiratoria adquieren un trascendente protagonismo requiriéndose de finos ajustes fisiológicos que garanticen la oxigenación celular. Asimismo, se exponen ciertos aspectos geofísicos, factores climáticos y otros condicionantes ambientales que limitan la viabilidad biológica y pueden afectar la salud respiratoria de los alpinistas situados en las cotas superiores de la troposfera a la latitud subtropical donde se encuentra ubicada dicha montaña. Actualmente cientos de alpinistas intentan alcanzar la cumbre del Mt. Everest todos los años, pero solo algunos consiguen su objetivo sin inhalar oxígeno suplementario, entre ellos algunos excepcionalmente dotados nativos Sherpa, protagonistas de insospechadas hazañas en la montaña más elevada de la superficie terrestre, cuya cima roza el límite fisiológico de supervivencia para el ser humano

Climbing to the highest height on Earth, the Mt. Everest (8.848 m), without supplementary oxygen equipment involves a physiological demand that is close to the maximum human tolerance. Exposures at extreme altitudes drastically conditions lung function, stores of oxygen and physical performance. This review brings interesting aspects about respiration, blood gases and aerobic exercise reported by those scientific projects that have carried out physiological measurements between 8,000 m and 8,848 m above sea level, under real or simulated altitude: the Operations "Everest I" (1946), "Everest II" (1985), "Everest III-COMEX" (1997), and the Expeditions "AMREE" (1981), "British 40th Anniversary Everest" (1993), and "Caudwell Xtrem Everest" (2007). These fascinating scientific research events, along with other outstanding biomedical expeditions performed above 5,500 m, like especially the "Silver Hut" (1960-61), "Italiana all’Everest" (1973), and "British Everest Medical" (1994), including those pioneer scientific reports made on the XIX century until the most recent research projects performed, have laid the foundations and knowledge on the human tolerance to such extreme levels of hypobaric hypoxia, where the lung, breathing and respiratory chain takes on a major role requiring fine physiological adjustments to ensure cellular oxygenation. Geophysical aspects, climatic factors and other environmental conditions that limit the biological viability and can affect the respiratory health of climbers on the upper troposphere zone at the subtropical latitude where that mountain is located are likewise reviewed and analyzed. Every year, hundreds of climbers try to reach the top of Mt. Everest, but only a few of them achieved their goal without inhaling supplemental oxygen, including some exceptionally gifted Sherpa natives, protagonist on unsuspected exploits in the highest mountain on terrestrial surface, whose summit touch the physiological limit of survival for the human being

A city scale study on the effects of intensive groundwater heat pump systems on heavy metal contents in groundwater.

As a result of the increasing use of shallow geothermal resources, hydraulic, thermal and chemical impacts affecting groundwater quality can be observed with ever increasing frequency (Possemiers et al., 2014). To overcome the uncertainty associated with chemical impacts, a city scale study on the effects of intensive geothermal resource use by groundwater heat pump systems on groundwater quality, with special emphasis on heavy metal contents was performed. Statistical analysis of geochemical data obtained from several field campaigns has allowed studying the spatiotemporal relationship between temperature anomalies in the aquifer and trace element composition of groundwater. The relationship between temperature and the concentrations of trace elements resulted in weak correlations, indicating that temperature changes are not the driving factor in enhancing heavy metal contaminations. Regression models established for these correlations showed a very low reactivity or response of heavy metal contents to temperature changes. The change rates of heavy metal contents with respect to temperature changes obtained indicate a low risk of exceeding quality threshold values by means of the exploitation regimes used, neither producing nor enhancing contamination significantly. However, modification of pH, redox potential, electrical conductivity, dissolved oxygen and alkalinity correlated with the concentrations of heavy metals. In this case, the change rates of heavy metal contents are higher, with a greater risk of exceeding threshold values.

Sensing Urban Patterns with Antenna Mappings: The Case of Santiago, Chile.

Mobile data has allowed us to sense urban dynamics at scales and granularities not known before, helping urban planners to cope with urban growth. A frequently used kind of dataset are Call Detail Records (CDR), used by telecommunication operators for billing purposes. Being an already extracted and processed dataset, it is inexpensive and reliable. A common assumption with respect to geography when working with CDR data is that the position of a device is the same as the Base Transceiver Station (BTS) it is connected to. Because the city is divided into a square grid, or by coverage zones approximated by Voronoi tessellations, CDR network events are assigned to corresponding areas according to BTS position. This geolocation may suffer from non negligible error in almost all cases. In this paper we propose "Antenna Virtual Placement" (AVP), a method to geolocate mobile devices according to their connections to BTS, based on decoupling antennas from its corresponding BTS according to its physical configuration (height, downtilt, and azimuth). We use AVP applied to CDR data as input for two different tasks: first, from an individual perspective, what places are meaningful for them? And second, from a global perspective, how to cluster city areas to understand land use using floating population flows? For both tasks we propose methods that complement or improve prior work in the literature. Our proposed methods are simple, yet not trivial, and work with daily CDR data from the biggest telecommunication operator in Chile. We evaluate them in Santiago, the capital of Chile, with data from working days from June 2015. We find that: (1) AVP improves city coverage of CDR data by geolocating devices to more city areas than using standard methods; (2) we find important places (home and work) for a 10% of the sample using just daily information, and recreate the population distribution as well as commuting trips; (3) the daily rhythms of floating population allow to cluster areas of the city, and explain them from a land use perspective by finding signature points of interest from crowdsourced geographical information. These results have implications for the design of applications based on CDR data like recommendation of places and routes, retail store placement, and estimation of transport effects from pollution alerts.