Folding Kinetics and Volume Variation of the ß-Hairpin Peptide Chignolin upon Ultrafast pH-Jumps.

In-depth characterization of fundamental folding steps of small model peptides is crucial for a better understanding of the folding mechanisms of more complex biomacromolecules. We have previously reported on the folding/unfolding kinetics of a model α-helix. Here, we study folding transitions in chignolin (GYDPETGTWG), a short ß-hairpin peptide previously used as a model to study conformational changes in ß-sheet proteins. Although previously suggested, until now, the role of the Tyr2-Trp9 interaction in the folding mechanism of chignolin was not clear. In the present work, pH-dependent conformational changes of chignolin were characterized by circular dichroism (CD), nuclear magnetic resonance (NMR), ultrafast pH-jump coupled with time-resolved photoacoustic calorimetry (TR-PAC), and molecular dynamics (MD) simulations. Taken together, our results present a comprehensive view of chignolin's folding kinetics upon local pH changes and the role of the Tyr2-Trp9 interaction in the folding process. CD data show that chignolin's ß-hairpin formation displays a pH-dependent skew bell-shaped curve, with a maximum close to pH 6, and a large decrease in ß-sheet content at alkaline pH. The ß-hairpin structure is mainly stabilized by aromatic interactions between Tyr2 and Trp9 and CH-π interactions between Tyr2 and Pro4. Unfolding of chignolin at high pH demonstrates that protonation of Tyr2 is essential for the stability of the ß-hairpin. Refolding studies were triggered by laser-induced pH-jumps and detected by TR-PAC. The refolding of chignolin from high pH, mainly due to the protonation of Tyr2, is characterized by a volume expansion (10.4 mL mol-1), independent of peptide concentration, in the microsecond time range (lifetime of 1.15 µs). At high pH, the presence of the deprotonated hydroxyl (tyrosinate) hinders the formation of the aromatic interaction between Tyr2 and Trp9 resulting in a more disorganized and dynamic tridimensional structure of the peptide. This was also confirmed by comparing MD simulations of chignolin under conditions mimicking neutral and high pH.

COVID-19-Associated Cognitive Biases on Pneumonia Differential Diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial information and establishing a diagnosis too early, with resistance to future adjustments. The latter happens when diagnoses more frequently considered are regarded as more common in reality. This case, in which the correct diagnosis was delayed due to these biases, highlights the need to remain aware of them as a means toward timely diagnosis and therapeutic success of pneumonia cases. An 84-year-old woman presented with a mild non-productive cough for two months and fever. She had a history of breast carcinoma treated with radiotherapy in the previous year. Computerized tomography (CT) showed extensive bilateral consolidation foci with ground-glass-opacification areas and bilateral pleural effusion, CO-RADS 3. COVID-19 with bacterial superinfection was suspected and levofloxacin was initiated. Nasopharyngeal swab polymerase chain reaction (PCR) was carried out three times, always negative for SARS-CoV-2. As the patient remained with fever and cough, the antibiotic was escalated to piperacillin/tazobactam and then to meropenem/vancomycin. She underwent bronchofibroscopy and alveolar lavage, with negative SARS-CoV-2 PCR. The re-evaluation CT scan maintained bilateral consolidations, with an aerial bronchogram. The biopsy of pulmonary consolidation allowed the diagnosis of radiation-induced organizing pneumonia. Prednisolone was initiated and achieved clinical remission and radiological improvement. This case highlights the need to remain aware of cognitive biases both when COVID-19 is suspected or ruled out and to consider other diagnoses when there is a lack of therapeutic response.

Fusion of Multimodal Imaging and 3D Digitization Using Photogrammetry.

Multimodal sensors capture and integrate diverse characteristics of a scene to maximize information gain. In optics, this may involve capturing intensity in specific spectra or polarization states to determine factors such as material properties or an individual's health conditions. Combining multimodal camera data with shape data from 3D sensors is a challenging issue. Multimodal cameras, e.g., hyperspectral cameras, or cameras outside the visible light spectrum, e.g., thermal cameras, lack strongly in terms of resolution and image quality compared with state-of-the-art photo cameras. In this article, a new method is demonstrated to superimpose multimodal image data onto a 3D model created by multi-view photogrammetry. While a high-resolution photo camera captures a set of images from varying view angles to reconstruct a detailed 3D model of the scene, low-resolution multimodal camera(s) simultaneously record the scene. All cameras are pre-calibrated and rigidly mounted on a rig, i.e., their imaging properties and relative positions are known. The method was realized in a laboratory setup consisting of a professional photo camera, a thermal camera, and a 12-channel multispectral camera. In our experiments, an accuracy better than one pixel was achieved for the data fusion using multimodal superimposition. Finally, application examples of multimodal 3D digitization are demonstrated, and further steps to system realization are discussed.

Global Assessment of Palliative Care Need: Serious Health-Related Suffering Measurement Methodology.

CONTEXT: Inequities and gaps in palliative care access are a serious impediment to health systems especially in low- and middle-income countries and the accurate measurement of need across health conditions is a critical step to understanding and addressing the issue. Serious Health-related Suffering (SHS) is a novel methodology to measure the palliative care need and was originally developed by The Lancet Commission on Global Access to Palliative Care and Pain Relief. In 2015, the first iteration - SHS 1.0 - was estimated at over 61 million people worldwide experiencing at least 6 billion days of SHS annually as a result of life-limiting and life-threatening conditions. OBJECTIVES: In this paper, an updated methodology - SHS 2.0 - is presented building on the work of the Lancet Commission and detailing calculations, data requirements, limitations, and assumptions. METHODS AND RESULTS: The updates to the original methodology focus on measuring the number of people who die with (decedents) or live with (non-decedents) SHS in a given year to assess the number of people in need of palliative care across health conditions and populations. Detail on the methodology for measuring the number of days of SHS that was pioneered by the Lancet Commission, is also shared, as this second measure is essential for determining the health system responses that are necessary to address palliative care need and must be a priority for future methodological work on SHS. CONCLUSIONS: The methodology encompasses opportunities for applying SHS to future policy making assessment of future research priorities particularly in light of the dearth of data from low- and middle-income countries, and sharing of directions for future work to develop SHS 3.0.

Screening of Microalgae for Bioactivity with Antiviral, Antibacterial, Anti-Inflammatory and Anti-Cancer Assays.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from thirty-three strains (including twenty dinoflagellates, four diatoms and nine strains from seven other algal classes), cultivated under identical conditions, were examined for their antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while the antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Significant differences were observed between species within the same class, in particular dinoflagellates, which were better represented in this study. These preliminary findings pave the way for an in-depth characterization of the extracts with highest signals in each test, the identification of the compounds responsible for the biological activities found and a further screening of the CCVIEO culture collection.

Nutrient-efficient catfish-based aquaponics for producing lamb's lettuce at two light intensities.

BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 µmol m-2 s-1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Diastereoselective (3 + 3)-Annulations of Trisubstituted Michael Acceptors for Access to Polyfunctional Cyclohexanones.

Michael-aldol domino reactions are powerful tools for rapidly assembling carbocyclic scaffolds. We herein disclose a base-catalyzed Michael-aldol domino reaction of trisubstituted Michael acceptors with ß-keto ester nucleophiles. The cyclohexanone products are obtained in excellent diastereoselectivity (up to >20:1 dr) and good yields (up to 84%). An attractive practical consideration is that pure products are isolated directly via filtration of the unpurified reaction mixtures. Further functionalization of the cyclohexanones is achieved without perturbation of stereocenters installed through the preceding annulation.

Nutritive Value and Bioactivities of a Halophyte Edible Plant: Crithmum maritimum L. (Sea Fennel).

Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel's salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.

Increasing the polarity of ß-lapachone does not affect its binding capacity with bovine plasma protein.

Despite ortho-quinones showing several biological and pharmacological activities, there is still a lack of biophysical characterization of their interaction with albumin - the main carrier of different endogenous and exogenous compounds in the bloodstream. Thus, the interactive profile between bovine serum albumin (BSA) with ß-lapachone (1) and its corresponding synthetic 3-sulfonic acid (2, under physiological pH in the sulphonate form) was performed. There is one main binding site of albumin for both ß-lapachones (n ≈ 1) and a static fluorescence quenching mechanism was proposed. The Stern-Volmer constant (KSV) values are 104 M-1, indicating a moderate binding affinity. The enthalpy (-3.41 ± 0.45 and - 8.47 ± 0.37 kJ mol-1, for BSA:1 and BSA:2, respectively) and the corresponding entropy (0.0707 ± 0.0015 and 0.0542 ± 0.0012 kJ mol-1 K-1) values indicate an enthalpically and entropically binding driven. Hydrophobic interactions and hydrogen bonding are the main binding forces. The differences in the polarity of 1 and 2 did not change significantly the affinity to albumin. In addition, the 1,2-naphthoquinones showed a similar binding trend compared with 1,4-naphthoquinones.

Development and construction of an open-platform, open-source low-cost portable uroflowmeter: The OpenFlow device.

BACKGROUND: Uroflowmetry is useful to screen for and manage many voiding disorders. Home-based uroflowmetry might better represent the patient's true voiding pattern and be more widely adopted if an accurate low-cost portable device was available. OBJECTIVE: Development and initial evaluation of an open-platform, open-source low-cost portable uroflowmeter. MATERIALS AND METHODS: We designed and built an uroflowmeter comprising of a load cell and digital memory card unit connected to a programmable microcontroller board mounted upon a 3D printed frame. It generated date-stamped tables which were processed and plotted. Twenty urologists were recruited to assess the device. Each participant received the equipment that was returned, along with a bladder diary, after at least 24 consecutive hours of homemade uroflowmetry recording. Additionally, were assessed with the International Prostatic Symptom Score (I-PSS) and Peeling diagram, whereas the device's ease of use, robustness, and portability were evaluated with a Likert-type questionnaire. Two experienced urodynamicists independently evaluated the tracings' quality rated with a 3° ordinal scale: (1) Interpretable without artifacts; (2) Interpretable with artifacts; (3) Uninterpretable. RESULTS: Participants' median age was 36.6 years old, none having an I-PSS > 5 or Peeling > 2. Overall 138 voidings were recorded (77 daytime, 61 nightly episodes). The device's ease of use, robustness, and portability obtained maximum score in 80% of evaluations. Most (98%) of the tracings were considered interpretable. Limitations included its small study population and short monitoring times. CONCLUSION: The construction of a cheap (<50 USD), accurate user-friendly portable uroflowmeter proved feasible, which could facilitate access to portable uroflowmetry.

Mental health help-seeking in Mexico.

Most people in need of mental health services in Mexico do not seek formal support or professional services to address their mental health needs. Understanding help-seeking behaviors is crucial to addressing underutilized mental health services and to leverage health promotion efforts. Data were collected as part of a larger research project on stigma and help-seeking for mental-health-related concerns in Mexico. A convenience sample of 469 adults residing in Mexico City participated in the study using an experimental vignette methodology assessing stigma toward individuals with mental health conditions, along with characteristics and demographic correlates of help-seeking. All survey measures were administered in Spanish. A structural regression was conducted for the outcome 'openness to professional help seeking for mental health problems' as a latent variable. Compared with males, females were more open to professional help seeking (b = 0.09, p = 0.038), as were people who endorsed higher spirituality (b = 0.01, p = 0.006); while people who experienced self-stigma were less open to professional help-seeking for mental health concerns (b = -0.15, p = 0.005). Self-stigma was a major driver of low service utilization. Contrary to previous studies, spirituality was a significant positive predictor of professional help-seeking. A more nuanced understanding of mental health help-seeking in Mexico can be useful for outreach efforts to increase service utilization both in Mexico and among Latinos in the United States (US). Given historical, geographic, and cultural ties with the US, it is important to understand mental health help-seeking in Mexico, which may relate directly to help-seeking behaviors in many US Latinos who have immigrated to the US. Directions for future research and practice implications are discussed, including a roadmap for health promotion activities.

Patterns of Avoidance Behavior in Response to Fear of Victimization in the Mexican Context: A Latent Class Analysis.

Fear of victimization (FOV) is a powerful determinant of behavior and prompts behavioral responses such as avoidance, associated with a decline in health-promoting activities and quality of life. Avoidance behaviors, which include constraining activities to perceived safe areas and avoiding areas regarded as unsafe, are of particular interest due to their high prevalence as a coping response to FOV and their link to adverse physical and mental health. Most research on FOV-related avoidance treats it as a single construct and have yet to elucidate the potential heterogeneity within this set of behaviors. We argue that such approach could mask potential heterogeneity among people who respond to FOV through avoidance and how they adapt to manage perceived risk. Our analysis extends the foundational knowledge regarding FOV-related avoidance using a person-centered approach. We attempted to capture distinct profiles across avoidance behaviors and how they are shaped by physical and social vulnerabilities. Data from the 2021 Mexico's National Survey of Victimization and Perception of Security Survey (n = 83,696) was analyzed using Latent Class Analysis focusing on 15 avoidance behaviors (e.g., stopped using public transportation). We conducted multinomial logistic regression to test whether age, gender, education, and neighborhood deprivation significantly predicted class membership. Findings revealed three classes: avoidant (most behavioral adjustments across the board), cautious (only adapted some behaviors), and protective (least behavioral adjustments, but more concerned about minors in their households). The results supported the hypothesized associations between age, gender, education, and neighborhood deprivation with group membership, but the significance differed by group. This research underscores the role of environmental context in shaping individual perceptions of safety and avoidance behavior. Finally, contrary to the approach of treating avoidance behavior as a single category, these findings present a more complex picture as distinct and meaningful patterns emerged across the three groups.

Acute Acetabular Protrusion: the Hardinge Approach for Implant Removal and One-stage Hip Reconstruction.

Acute penetration of a total hip arthroplasty into the pelvic cavity is a grave and potentially catastrophic scenario. Fortunately, this complication is uncommon and rarely encountered during a surgical career. Currently, a two-stage procedure is favoured by most surgeons, but the evidence for this is unconvincing and may expose the patient to unnecessary risks. Furthermore, a two-stage approach may be more suitable for the more common chronic migration of a loose acetabular shell, which fundamentally differs from acute pelvic penetration. We present the case of a 76-year-old man referred to our institution for reconstructive surgery following acute pelvic penetration of the acetabular shell during total hip arthroplasty. We used a single-stage Hardinge approach to retrieve the shell and successfully reconstruct the acetabulum. Specific indications for using this method are proposed. In carefully selected cases of intrapelvic implants, a single-stage method can improve patient outcomes while minimising unnecessary risks associated with the conventional two-stage approach.

The development of an advanced diploma program for palliative care leaders in Chile.

Context: The majority of people with serious health-related suffering in low- and middle-income countries lack access to palliative care (PC). Increased access to PC education is greatly needed. Objectives: This paper describes the process to adapt an advanced PC training course for a Chilean context. Methods: A joint team of intercultural PC educators from the US and Chile conducted a series of key informant interviews and a target audience survey to iteratively design a PC training course in Chile. Results: Eight key informant interviews identified a strong need for formal PC education pathways, confirmed the five central learning domains, and helped to identify potential course sub-topics. A target audience survey of 59 PC providers from across Chile confirmed a strong desire to participate in such a course. Conclusion: Our team of intercultural PC educators adapted an advanced PC course to the unique context of Chilean providers.

Improving Adherence to Physical Therapy in the Development of Serious Games: Conceptual Framework Design Study.

BACKGROUND: Insufficient levels of treatment adherence can have adverse effects on the outcomes of physical rehabilitation. To address this issue, alternative approaches to traditional therapies, such as serious games, have been designed to enhance adherence. Nevertheless, there remain gaps in the development of serious games concerning the effective implementation of motivation, engagement, and the enhancement of treatment adherence. OBJECTIVE: This study aims to design a conceptual framework for the development of serious games that incorporate essential adherence factors to enhance patient compliance with physical rehabilitation programs. METHODS: We formulated a conceptual framework using iterative techniques inspired by a conceptual framework analysis. Initially, we conducted a comprehensive literature review, concentrating on the critical adherence factors in physical rehabilitation. Subsequently, we identified, categorized, integrated, and synthesized the concepts derived from the literature review to construct the conceptual framework. RESULTS: The framework resembles a road map, comprising 3 distinct phases. In the initial phase, the patient's characteristics are identified through an initial exploration. The second phase involves the development of a serious game, with a focus on enhancing treatment adherence by integrating the key adherence factors identified. The third phase revolves around the evaluation of the serious game. These phases are underpinned by 2 overarching themes, namely, a user-centered design and the GameFlow model. CONCLUSIONS: The conceptual framework offers a detailed, step-by-step guide for creating serious games that incorporate essential adherence factors, thereby contributing to improved adherence in the physical rehabilitation process. To establish its validity, further evaluations of this framework across various physical rehabilitation programs and user groups are necessary.

Non-pharmaceutical interventions to combat COVID-19 in the Americas described through daily sub-national data.

This dataset covers national and subnational non-pharmaceutical interventions (NPI) to combat the COVID-19 pandemic in the Americas. Prior to the development of a vaccine, NPI were governments' primary tools to mitigate the spread of COVID-19. Variation in subnational responses to COVID-19 is high and is salient for health outcomes. This dataset captures governments' dynamic, varied NPI to combat COVID-19 for 80% of Latin America's population from each country's first case through December 2021. These daily data encompass all national and subnational units in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru. The dataset includes individual and aggregate indices of nine NPI: school closures, work suspensions, public event cancellations, public transport suspensions, information campaigns, local travel restrictions, international travel controls, stay-at-home orders, and restrictions on the size of gatherings. We also collected data on mask mandates as a separate indicator. Local country-teams drew from multiple data sources, resulting in high-quality, reliable data. The dataset thus allows for consistent, meaningful comparisons of NPI within and across countries during the pandemic.

Corrigendum: Consistent long-term therapeutic efficacy of human umbilical cord matrix-derived mesenchymal stromal cells after myocardial infarction despite individual differences and transient engraftment.

[This corrects the article DOI: 10.3389/fcell.2021.624601.].

Exploiting Potential Probiotic Lactic Acid Bacteria Isolated from Chlorella vulgaris Photobioreactors as Promising Vitamin B12 Producers.

Lactic acid bacteria (LAB) have been documented as potential vitamin B12 producers and may constitute an exogenous source of cobalamin for the microalga Chlorella vulgaris, which has been described as being able to perform vitamin uptake. Hence, there is an interest in discovering novel B12-producing probiotic LAB. Therefore, the purpose of the current work was to perform a phenotype-genotype analysis of the vitamin B12 biosynthesis capacity of LAB isolated from C. vulgaris bioreactors, and investigate their probiotic potential. Among the selected strains, Lactococcus lactis E32, Levilactobacillus brevis G31, and Pediococcus pentosaceus L51 demonstrated vitamin B12 biosynthesis capacity, with the latter producing the highest (28.19 ± 2.27 pg mL-1). The genomic analysis confirmed the presence of pivotal genes involved in different steps of the biosynthetic pathway (hemL, cbiT, cobC, and cobD). Notably, P. pentosaceus L51 was the only strain harboring cobA, pduU, and pduV genes, which may provide evidence for the presence of the cobalamin operon. All strains demonstrated the capability to withstand harsh gastrointestinal conditions, although P. pentosaceus L51 was more resilient. The potential for de novo cobalamin biosynthesis and remarkable probiotic features highlighted that P. pentosaceus L51 may be considered the most promising candidate strain for developing high-content vitamin B12 formulations.

Upper and Lower Limbs Acute Fatigue Did Not Mitigate Male Trained Air Force Soldiers' Marksmanship.

In this study, we aimed to investigate the impact of acute fatigue on pistol shooting performance among Air Force marksmen. We compared the accuracy, precision, speed-accuracy trade-off, shooting cycle time, and hits on a silhouette target among 12 Brazilian Air Force servicemen (M age = 21.5, SD - 1.6 years) under both fatigue and non-fatigue conditions in a crossover design. In the fatigued condition, the participants performed a fatigue protocol composed of side runs, vertical jumps, push-ups, running, and burpees exercises before shooting. Participants performed the countermovement jump and the plyometric push-ups tests on a contact mat before and immediately after the fatigue protocol to compare the heights achieved pre- and post-fatigue. Paired t-tests showed a significant performance reduction of 34.36% and 40.02% for the countermovement jump and plyometric push-ups, respectively, indicating that participants were fatigued in their lower and upper limbs. In the non-fatigued condition, no exercise was performed before shooting. Results indicated no significant differences between conditions on shooting precision (p = .125; ES: .54), speed-accuracy trade-off (p = .261; ES = .33), hits within the silhouette (p = .167; ES = .41), or shooting cycle times (p = .868; ES = .05); but accuracy was greater (p = .025; ES: .54) when fatigued. We concluded that overall shooting performance was not impaired by physical fatigue, and shooting accuracy appeared to be improved. Perhaps physical fatigue was not enough to impair shooting accuracy in this young adult group, as accuracy decline is expected instead when shooters are in an exhausted state. Further research is needed to confirm these findings and test this presumption.