Highly-selective optical filter for NADH fluorescence detection in multiphoton microscopy.

Colorectal cancer (CRC) is a pressing global health concern, emphasizing the need for early detection tools. In this study an optical filter for precise detection of nicotinamide adenine dinucleotide (NADH) fluorescence via two-photon excitation fluorescence (TPEF) was developed. Fabricated with silicon dioxide and titanium dioxide thin films in a Fabry-Perot structure, the filter achieved a peak transmittance of about 95% at 483 nm, with a 12 nm full-width at half maximum. TPEF measurements using a tailored setup and NADH liquid phantoms underscored the filter's significance in selectively capturing NADH fluorescence while mitigating interference from other fluorophores. This work marks a substantial stride towards integrating multiphoton microscopy into conventional colonoscopy, enabling non-invasive, objective optical biopsy for colorectal tissue analysis. Further refinements of the experimental setup are imperative to advance tissue differentiation and enhance CRC diagnosis.

Multifractal analysis of maize and soybean DNA.

This paper investigates the complexity of DNA sequences in maize and soybean using the multifractal detrended fluctuation analysis (MF-DFA) method, chaos game representation (CGR), and the complexity-entropy plane approach. The study aims to understand the patterns and structures of these DNA sequences, which can provide insights into their genetic makeup and improve crop yield and quality. The results show that maize and soybean DNA sequences exhibit fractal properties, indicating a complex and self-organizing structure. We observe the persistence trend between sequences of base pairs, which indicates long-range correlations between base pairs. We also identified the stochastic nature of the DNA sequences of both species.

Use of oxygen therapy for pneumocephalus: a systematic review.

Pneumocephalus is the pathologic collection of air in the intracranial cavity. In sufficient volumes, it can contribute to symptoms ranging from headaches to death. For conservative treatment, oxygen use is commonplace. Although this is an accepted tenet of clinical practice, it is not necessarily founded on robust trials. An electronic search of databases EMBASE and MEDLINE and the Cochrane Library was undertaken as per the 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Three articles were included. Although the modes of oxygen delivery were heterogenous (non-rebreather versus endotracheal versus hyperbaric chamber), all studies concluded favorably on the use of oxygen therapy for increased reabsorption of pneumocephalus.

Influence of transducer pressure and examiner experience on muscle active shear modulus measured by shear wave elastography.

INTRODUCTION: This study examined the effects of ultrasound transducer pressure and examiner experience on the biceps femoris long head and semitendinosus muscle active shear modulus in healthy individuals (n = 28). METHODS: Active shear modulus was assessed using shear wave elastography at 20% of knee flexor maximal voluntary isometric contraction. Examiners with different experience levels measured the muscles' shear modulus with three pressure levels: mild, moderate, and hard. RESULTS: A main effect of transducer pressure was found for both biceps femoris long head (p < 0.001; η2p = 0.314) and semitendinosus muscles (p < 0.001; η2p = 0.280), whereas differences were found between mild-moderate (biceps femoris long head: p = 0.013, d = 0.23; semitendinosus: p = 0.024, d = 0.25), and mild-hard pressures (biceps femoris long head: p = 0.001, d = 0.47; semitendinosus: p = 0.002, d = 0.47). Examiners performed similar shear modulus measurements in the biceps femoris long head (p = 0.299; η2p = 0.041) and semitendinosus (p = 0.177; η2p = 0.066), although the experienced examiner showed a higher measurement repeatability (biceps femoris long head: ICC = 0.86-0.95, semitendinosus: ICC = 0.89-0.96; vs. biceps femoris long head: ICC = 0.78-0.87, semitendinosus: ICC = 0.66-0.87). CONCLUSION: Transducer pressure influences the active shear modulus measurement between mild and moderate or hard pressures. Additionally, examiner experience seems to have no influence on muscle active shear modulus measurement when assessed at the same site (using casts). IMPLICATIONS FOR PRACTICE: Future studies assessing active muscle shear modulus should use mild transducer pressure and having experienced examiners in order to improve measurement reliability.

Sedimentation velocity FDS studies of antibodies in pooled human serum.

The biotech industry has great interest in investigating therapeutic proteins in high concentration environments like human serum. The fluorescence detection system (Aviv-FDS) allows the performance of analytical ultracentrifuge (AUC) sedimentation velocity (SV) experiments in tracer or BOLTS protocols. Here, we compare six pooled human serum samples by AUC SV techniques and demonstrate the potential of this technology for characterizing therapeutic antibodies in serum. Control FDS SV experiments on serum alone reveal a bilirubin-HSA complex whose sedimentation is slowed by solution nonideality and exhibits a Johnston-Ogston (JO) effect due to the presence of high concentrations of IgG. Absorbance SV experiments on diluted serum samples verify the HSA-IgG composition as well as a significant IgM pentamer boundary at 19 s. Alexa-488 labeled Simponi (Golimumab) is used as a tracer to investigate the behavior of a therapeutic monoclonal antibody (mAb) in serum, and the sedimentation behavior of total IgG in serum. Serum dilution experiments allow extrapolation to zero concentration to extract so, while global direct boundary fitting with SEDANAL verifies the utility of a matrix of self- and cross-term phenomenological nonideality coefficients (ks and BM1) and the source of the JO effect. The best fits include weak reversible association (~ 4 × 103 M-1) between Simponi and total human IgG. Secondary mAbs to human IgG and IgM verify the formation of a 10.2 s 1:1 complex with human IgG and a 19 s complex with human IgM pentamers. These results demonstrate that FDS AUC allows a range of approaches for investigating therapeutic antibodies in human serum.

Simulation of Gilbert theory for self-association in sedimentation velocity experiments: a guide to evaluate best fitting models.

There is a long tradition in the Biophysics community of using simulations as a means to understand macromolecular behavior in various physicochemical methods. This allows a rigorous means to interpret observations in terms of fundamental principles, including chemical equilibrium, reaction kinetics, transport processes and thermodynamics. Here we simulate data for the Gilbert Theory for self-association, a fundamental analytical ultracentrifuge (AUC) technique to understand the shape of sedimentation velocity reaction boundaries that involve reversible monomer-Nmer interactions. Simulating monomer-dimer through monomer-hexamer systems as a function of concentration about the equilibrium constant allows a visual means to differentiate reaction stoichiometry by determining end points and inflection positions. Including intermediates (eg A1-A2-A3-A4-A5-A6) in the simulations reveals the smoothing of the reaction boundary and the removal of sharp inflections between monomers and polymers. The addition of cooperativity restores sharp boundaries or peaks to the observation and allows more discrimination in the selection of possible fitting models. Thermodynamic nonideality adds additional features when applied across wide ranges of concentration that might be appropriate for high-concentration therapeutic monoclonal antibody (mAb) solutions. This presentation serves as a tutorial for using modern AUC analysis software like SEDANAL for selecting potential fitting models.

Error perception classification in Brain-Computer Interfaces using CNN.

Capturing the error perception of a human interacting with a Brain-Computer Interface (BCI) is a key piece in improving the accuracy of these systems and making the interaction more seamless. Convolutional Neural Networks (CNN) have recently been applied for this task rendering the model free of feature-selection. We propose a new model with shorter temporal input trying to approximate its usability to that of a real-time BCI application. We evaluate and compare our model with some other recent CNN models using the Monitoring Error-Related Potential dataset, obtaining an accuracy of 80% with a sensitivity and specificity of 76% and 85%, respectively. These results outperform previous models. All models are made available online for reproduction and peer review.

Design, simulation, and fabrication of an ingestible capsule with gastric balloon for obesity treatment.

The treatment of obesity based only on lifestyle changes has been shown ineffectiveness in a long-term period. The development of more definitive and non-invasive therapies has been the subject of study. In this paper, a magnetically driven ingestible capsule with the capacity to inflate a gastric balloon is devised, simulated, and fabricated. The balloon is inflated to a volume of 150 ml using an acid-base reaction between citric acid and potassium bicarbonate. Finite element method simulations were performed to study the interaction between the permanent external magnet and the ingestible capsule and confirm the magnetic activation mechanism. A fabrication process was proposed to manufacture a polydimethylsiloxane (PDMS) balloon in a simple, functional, and reproducible way. The two layers and 1:8 ratio balloons are the most cost-effective without compromising their mechanical properties. The capsule body parts manufactured by a three-dimensional (3D) printing process - Digital Light Processing (DLP) showed high accuracy and excellent resolution. This study demonstrated that the proposed ingestible capsule would successfully inflate the gastric balloon to treat obesity.

Use of the socio-ecological model to explore factors that influence the implementation of a diabetes structured education programme (EXTEND project) inLilongwe, Malawi and Maputo, Mozambique: a qualitative study.

BACKGROUND: Diabetes Self-Management Education and Support (DSMES) programmes are vital for type 2 diabetes mellitus (T2DM) management. However, they are limited in Sub-Saharan Africa (SSA). To address this gap, a DSMES, namedEXTEND was developed in Lilongwe (Malawi) and Maputo (Mozambique). This qualitative study aimed to explore factors that influence the implementation of DSMES in these settings. METHODS: The Socio-ecological model was applied to explore factors influencing the implementation of DSMES in SSA. Data was analysed using the Framework method and constant comparative techniques. Sixty-six people participated in the study: people with T2DM who participated in the EXTEND programme; healthcare professionals (HCPs), EXTEND educators, EXTEND trainers, and stakeholders. RESULTS: Our findings indicate that there is a need to develop an integrated and dedicated diabetes services in SSA healthcare systems, incorporating culturally adapted DSMES and tailored diabetes training to all professions involved in diabetes management. Traditional media and the involvement of community leaders were proposed as important elements to help engage and promote DSMES programmes in local communities. During the design and implementation of DSMES, it is important to consider individual and societal barriers to self-care. CONCLUSION: Findings from this study suggest that multi-faceted factors play a significant role to the implementation of DSMES programmes in LICs. In the future, EXTEND could be incorporated in the development of diabetes training and dedicated diabetes services in SSA healthcare systems, acting as an educational tool for both people with T2DM and HCPs. This project was supported by the Medical Research Council GCRF NCDs Foundation Awards 2016 Development Pathway Funding.

Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.

Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.

Analysis of nonideality: insights from high concentration simulations of sedimentation velocity data.

The Aviv fluorescence detection system (Aviv-FDS) has allowed the performance of sedimentation velocity experiments on therapeutic antibodies in highly concentrated environments like formulation buffers and serum. Methods were implemented in the software package SEDANAL for the analysis of nonideal, weakly associating AUC data acquired on therapeutic antibodies and proteins (Wright et al. Eur Biophys J 47:709-722, 2018, Anal Biochem 550:72-83, 2018). This involved fitting both hydrodynamic, ks, and thermodynamic, BM1, nonideality where concentration dependence is expressed as s = so/(1 + ksc) and D = Do(1 + 2BM1c)/(1 + ksc) and so and Do are values extrapolated to c = 0 (mg/ml). To gain insight into the consequences of these phenomenological parameters, we performed simulations with SEDANAL of a monoclonal antibody as a function of ks (0-100 ml/g) and BM1 (0-100 ml/g). This provides a visual understanding of the separate and joint impact of ks and BM1 on the shape of high-concentration sedimentation velocity boundaries and the challenge of their unique determination by finite element methods. In addition, mAbs undergo weak self- and hetero-association (Yang et al. Prot Sci 27:1334-1348, 2018) and thus we have simulated examples of nonideal weak association over a wide range of concentrations (1-120 mg/ml). Here we demonstrate these data are best analyzed by direct boundary global fitting to models that account for ks, BM1 and weak association. Because a typical clinical dose of mAb is 50-200 mg/ml, these results have relevance for biophysical understanding of concentrated therapeutic proteins.

Direct Structural Identification and Quantification of the Split-Vacancy Configuration for Implanted Sn in Diamond.

We demonstrate formation of the ideal split-vacancy configuration of the Sn-vacancy center upon implantation into natural diamond. Using ß^{-} emission channeling following low fluence ^{121}Sn implantation (2×10^{12} atoms/cm^{2}, 60 keV) at the ISOLDE facility at CERN, we directly identified and quantified the atomic configurations of the Sn-related centers. Our data show that the split-vacancy configuration is formed immediately upon implantation with a surprisingly high efficiency of ≈40%. Upon thermal annealing at 920 °C ≈30% of Sn is found in the ideal bond-center position. Photoluminescence revealed the characteristic SnV^{-} line at 621 nm, with an extraordinarily narrow ensemble linewidth (2.3 nm) of near-perfect Lorentzian shape. These findings further establish the SnV^{-} center as a promising candidate for single photon emission applications, since, in addition to exceptional optical properties, it also shows a remarkably simple structural formation mechanism.

Local inhomogeneous state in multiferroic SmCrO3.

Rare-earth orthochromites with distorted perovskite structure (e.g. RCrO3, R = Sm, Gd) have been under strong debate with respect to the origin of their ferroelectric order. Of particular interest is the question of whether such orthochromites are, in fact, magnetically driven improper ferroelectrics, as many rare-earth manganites or orthoferrites. Here we show, by studying at the atomic scale the rare-earth SmCrO3 system that a distortion of the Sm local environment emerges within the paramagnetic phase, near room temperature. Our Electric Field Gradient measurements combined with first-principles calculations show that the emergent phase cannot be simply ascribed to the Pna21 structure as reported for GdCrO3 or SmCrO3. Instead a local inhomogeneous state, where regular non-polar and polar distorted environments coexist, develops at low temperatures.

Studying electronic properties in GaN without electrical contacts using γ-γ vs e--γ Perturbed Angular Correlations.

The potential use of combined e--γ vs γ-γ Perturbed Angular Correlations (PAC) experiments as a possible alternative to study electronic properties of materials and/or samples where Hall effect measurements are difficult to perform due to low-quality ohmic contacts is here demonstrated using Si- and Zn-doped GaN samples as a showcase example. To do so, the lattice site of implanted 181Hf/181Ta and the recombination of Ta ionized and excited electronic states were studied as a function of temperature and sample doping in GaN. By combining the γ-γ and e--γ PAC results with Density Functional Theory simulations, it was possible to assign a single stable site with a double-donor character for Ta in GaN. A metastable charge state was also identified at particular temperatures using e--γ PAC. A thermally activated process was observed for the electronic recombination at high temperatures with activation energies of 15(2) meV and 12(1) meV for the Si- and Zn-doped samples, respectively, and attributed to Si shallow donors present in both samples. A reduced number of available electrons was observed in the Zn-doped sample due to donor compensation by the Zn acceptors. At low temperatures, it is suggested that the recombination process occurs via Variable Range Hopping. The doping characteristics of both samples were successfully distinguished.

Position Statement on Atopic Dermatitis in Sub-Saharan Africa: current status and roadmap.

BACKGROUND: The first International Society of Atopic Dermatitis (ISAD) global meeting dedicated to atopic dermatitis (AD) in Sub-Saharan Africa (SSA) was held in Geneva, Switzerland in April 2019. A total of 30 participants were present at the meeting, including those from 17 SSA countries, representatives of the World Health Organization (WHO), the International Foundation for Dermatology (IFD) (a committee of the International League of Dermatological Societies, ILDS www.ilds.org), the Fondation pour la Dermatite Atopique, as well as specialists in telemedicine, artificial intelligence and therapeutic patient education (TPE). RESULTS: AD is one of the most prevalent chronic inflammatory skin diseases in SSA. Besides neglected tropical diseases (NTDs) with a dermatological presentation, AD requires closer attention from the WHO and national Departments of Health. CONCLUSIONS: A roadmap has been defined with top priorities such as access to essential medicines and devices for AD care, in particular emollients, better education of primary healthcare workers for adequate triage (e.g. better educational materials for skin diseases in pigmented skin generally and AD in particular, especially targeted to Africa), involvement of traditional healers and to a certain extent also patient education, bearing in mind the barriers to effective healthcare faced in SSA countries such as travel distances to health facilities, limited resources and the lack of dermatological expertise. In addition, several initiatives concerning AD research in SSA were discussed and should be implemented in close collaboration with the WHO and assessed at follow-up meetings, in particular, at the next ISAD meeting in Seoul, South Korea and African Society of Dermatology and Venereology (ASDV) meeting in Nairobi, Kenya, both in 2020.

Trophoblast function is altered by decidual factors in gestational-dependant manner.

Inadequate implantation and placentation is associated with miscarriage and placental insufficiency. The decidual environment is thought to regulate trophoblast invasion, however this is poorly defined in humans. We aimed to determine the effect of decidualization on trophoblast function. In vitro decidualized primary human endometrial stromal cells (HESC) significantly enhanced first-trimester extravillous trophoblast (EVT) (6-8-weeks gestation) adhesion, outgrowth/invasion. In EVTs from 10 to 12-weeks gestation this effect was absent (adhesion, invasion) or reversed (outgrowth). HESC conditioned media had no effect on trophoblast MMP9 production/activity. Decidualization regulated EVT function in a gestational-dependent manner. This study highlights the importance of trophoblast-decidual synchrony.

La Medicina Interna y su futuro en los sistemas de salud. Posicionamiento de la Sociedad Española de Medicina Interna y de la Sociedad Portuguesa de Medicina Interna / Internal Medicine and its future in health systems. Positioning Statement of the Spanish Society of Internal Medicine and the Portuguese Society of Internal Medicine

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