A new genus of Herpyllobiidae (Copepoda: Cyclopoida) from a deep-living annelid (Polychaeta: Sigalionidae).

A taxonomic study of deep-sea polychaetes collected at a depth of 2,805 m off the northern coast of California revealed a scaleworm of the family Sigalionidae with an attached parasitic copepod. The copepod represents an undescribed genus of the family Herpyllobiidae, comprising mesoparasitic copepods chiefly recorded from polychaetes of the family Polynoidae. Blakerius gen. nov. diverges from the other herpyllobiid genera by its possession of 1) a chalice-shaped ectosoma with several protuberances along the posterior margin and a long cylindrical shaft with a hyaline coating and integumental sculpturing, a short stalk with a small, anteriorly placed sclerotized ring, 2) a relatively large, discoid-shaped endosoma with digitiform process, and 3) attached male copepodids with 3-segmented antennules, containing limbless sac-like males. The new genus is compared with other herpyllobiids. This discovery increases the number of known herpyllobiid genera to six and is the first record of a herpyllobiid parasitizing a sigalionid polychaete.urn: lsid: zoobank.org:pub:5E31FEED-D3EB-460E-AEA4-02A9D3A778D6.

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: Discover study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Clay-polymer hybrid hydrogels in the vanguard of technological innovations for bioremediation, metal biorecovery, and diverse applications.

Polymeric hydrogels are among the most studied materials due to their exceptional properties for many applications. In addition to organic and inorganic-based hydrogels, "hybrid hydrogels" have been gaining significant relevance in recent years due to their enhanced mechanical properties and a broader range of functionalities while maintaining good biocompatibility. In this sense, the addition of micro- and nanoscale clay particles seems promising for improving the physical, chemical, and biological properties of hydrogels. Nanoclays can contribute to the physical cross-linking of polymers, enhancing their mechanical strength and their swelling and biocompatibility properties. Nowadays, they are being investigated for their potential use in a wide range of applications, including medicine, industry, and environmental decontamination. The use of microorganisms for the decontamination of environments impacted by toxic compounds, known as bioremediation, represents one of the most promising approaches to address global pollution. The immobilization of microorganisms in polymeric hydrogel matrices is an attractive procedure that can offer several advantages, such as improving the preservation of cellular integrity, and facilitating cell separation, recovery, and transport. Cell immobilization also facilitates the biorecovery of critical materials from wastes within the framework of the circular economy. The present work aims to present an up-to-date overview on the different "hybrid hydrogels" used to date for bioremediation of toxic metals and recovery of critical materials, among other applications, highlighting possible drawbacks and gaps in research. This will provide the latest trends and advancements in the field and contribute to search for effective bioremediation strategies and critical materials recovery technologies.

Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study.

BACKGROUND: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. METHODS: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. FINDINGS: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. CONCLUSIONS: Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients-A Comprehensive Review.

Multiple sclerosis (MS) is characterized by a variety of symptoms that have a major impact on quality of life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem and sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations of MS have a detrimental effect on overall functioning and quality of life, such as cognitive impairment, depression, anxiety, fatigue, and pain. However, when talking about QoL, categorical definitions cannot be used because although the concept is generally understood, it is highly nuanced. Suffering from MS can significantly reduce QoL. Numerous research studies have focused on trying to identify and assess which are the elements that most affect the loss of QoL in MS people. However, in addition to the fact that the measurement of QoL can be subjective, it is very difficult to consider these elements in isolation, as they are interrelated. One such limiting factor of QoL that has been investigated is cognitive impairment (CI). This has been shown to have an impact on the lives of MS people, although the different approaches that have been taken to assess CI have evident limitations.

Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.

BACKGROUND: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course. METHODS: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis. RESULTS: In total, 11 245 participants were included of which 93.7% (n=10 533) were persons with relapsing-remitting MS (RRMS). In RRMS, the presence of CSF oligoclonal bands (OCBs) was associated with shorter time to disability milestones EDSS 4 (adjusted HR=1.272 (95% CI, 1.089 to 1.485), p=0.002), EDSS 6 (HR=1.314 (95% CI, 1.062 to 1.626), p=0.012) and EDSS 7 (HR=1.686 (95% CI, 1.111 to 2.558), p=0.014). On the other hand, the presence of CSF pleocytosis (≥5 cells/µL) increased time to moderate disability (EDSS 4) in RRMS (HR=0.774 (95% CI, 0.632 to 0.948), p=0.013). None of the CSF variables were associated with time to disability milestones in persons with primary progressive MS (PPMS). The presence of CSF pleocytosis increased ARR2 in RRMS (adjusted R2=0.036, p=0.015). CONCLUSIONS: In RRMS, the presence of CSF OCBs predicts shorter time to disability milestones, whereas CSF pleocytosis could be protective. This could however not be found in PPMS. CSF pleocytosis is associated with short-term inflammatory disease activity in RRMS. CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making.

Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes.

Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1ß mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.

Comparative Study between the Diagnostic Effectiveness of Brain SPECT with [123I]Ioflupane and [123I]MIBG Scintigraphy in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease. It has a fast progression, so early diagnosis is decisive. Two functional imaging tests can be involved in its diagnosis: [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. Our aim is to comparatively analyze the diagnostic performance of both techniques. METHODS: 46 patients (24 males and 22 females) with MSA underwent [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. In each of these techniques, qualitative assessment was compared with quantitative assessment. RESULTS: SPECT visual assessment was positive in 93.5% of subjects (S = 95.24%; PPV = 93.02%). A cut-off of 1.363 was established for overall S/O index (S = 85.7%, E = 100%). Visual assessment of scintigraphy was positive in 73.1% (S = 78.57%, PPV = 94.29%). For the delayed heart/medistinum ratio (HMR) a cut-off of 1.43 (S = 85.3, E = 100%) was obtained. For each unit increase in delayed HMR, the suspicion of MSA increased by 1.58 (OR = 1.58, p < 0.05). The quantitative assessment showed an association with the visual assessment for each technique (p < 0.05). CONCLUSIONS: Both tests are useful in MSA diagnosis. Comparatively, we did not observe a clear superiority of either. Striatal and myocardial deterioration do not evolve in parallel. Qualitative assessment is crucial in both techniques, together with the support of quantitative analysis. Delayed HMR shows a direct relationship with the risk of MSA.

Exploring Maternal and Infant Health App Development and Effectiveness Research: Scoping Review.

BACKGROUND: Globally, high rates of maternal and infant mortality call for interventions during the perinatal period to engage pregnant people as well as their loved ones in care. Mobile health technologies have become ubiquitous in our lives and in health care settings. However, there is a need to further explore their safety and effectiveness to support and improve health outcomes locally and globally. OBJECTIVE: The aim of this study was to review and synthesize published literature that described the development process or effectiveness evaluations of maternal and infant apps. METHODS: We applied a methodological framework for scoping reviews as well as the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines; in addition, the systematic review platform Covidence (Veritas Health Innovation Ltd) was used to facilitate the review of included studies. Search terms were developed collaboratively, and health sciences-associated databases were searched for studies conducted between January 1, 2000, and February 4, 2022. We excluded studies about apps that only gathered or tracked data or targeted care providers. RESULTS: A total of 1027 articles were included for title and abstract screening, of which 87 (8.47%) were chosen for full-text screening. Of these 87 articles, 74 (85%) were excluded with reasons, and 19 (22%) were included. Four articles were added at data extraction from hand searching and 2 others were excluded. Thus, we reviewed and synthesized data from 11 unique studies reported in 21 articles published between 2017 and 2021. The included studies represented 8 different countries. Most of the apps (8/11, 73%) were in English, although apps were also developed in Arabic, Bahasa Indonesia, and Nepali. The articles reviewed revealed the early stage of development of the field of maternal and infant health apps, with modest evidence of app use and achievement of study outcomes. Only 1 (9%) of the 11 apps was endorsed by an independent health care provider society. App development and evaluation processes emerged, and specific app features were identified as vital for well-functioning apps. End-user engagement occurred in some, but not all, parts of app research and development. CONCLUSIONS: Apps to improve maternal and infant health are being developed and launched in enormous numbers, with many of them not developed with mothers' needs in mind. There are concerns about privacy, safety, and the standardization of current apps as well as a need for professional or institution-specific guidelines or best practices. Despite challenges inherent in currently available apps and their design processes, maternal and infant app technology holds promise for achieving health equity goals and improving maternal and child health outcomes. Finally, we propose recommendations for advancing the knowledge base for maternal and infant apps.

Soft-metal(loid)s induce protein aggregation in Escherichia coli.

Metal(loid) salts were used to treat infectious diseases in the past due to their exceptional biocidal properties at low concentrations. However, the mechanism of their toxicity has yet to be fully elucidated. The production of reactive oxygen species (ROS) has been linked to the toxicity of soft metal(loid)s such as Ag(I), Au(III), As(III), Cd(II), Hg(II), and Te(IV). Nevertheless, few reports have described the direct, or ROS-independent, effects of some of these soft-metal(loid)s on bacteria, including the dismantling of iron-sulfur clusters [4Fe-4S] and the accumulation of porphyrin IX. Here, we used genome-wide genetic, proteomic, and biochemical approaches under anaerobic conditions to evaluate the direct mechanisms of toxicity of these metal(loid)s in Escherichia coli. We found that certain soft-metal(loid)s promote protein aggregation in a ROS-independent manner. This aggregation occurs during translation in the presence of Ag(I), Au(III), Hg(II), or Te(IV) and post-translationally in cells exposed to Cd(II) or As(III). We determined that aggregated proteins were involved in several essential biological processes that could lead to cell death. For instance, several enzymes involved in amino acid biosynthesis were aggregated after soft-metal(loid) exposure, disrupting intracellular amino acid concentration. We also propose a possible mechanism to explain how soft-metal(loid)s act as proteotoxic agents.

Natural and Engineered Isoforms of the Inflammasome Adaptor ASC Form Noncovalent, pH-Responsive Hydrogels.

The protein ASC polymerizes into intricate filament networks to assemble the inflammasome, a filamentous multiprotein complex that triggers the inflammatory response. ASC carries two Death Domains integrally involved in protein self-association for filament assembly. We have leveraged this behavior to create noncovalent, pH-responsive hydrogels of full-length, folded ASC by carefully controlling the pH as a critical factor in the polymerization process. We show that natural variants of ASC (ASC isoforms) involved in inflammasome regulation also undergo hydrogelation. To further demonstrate this general capability, we engineered proteins inspired by the ASC structure that also form hydrogels. We analyzed the structural network of the natural and engineered protein hydrogels using transmission and scanning electron microscopy and studied their viscoelastic behavior using shear rheology. Our results reveal one of the very few examples of hydrogels created by the self-assembly of globular proteins and domains in their native conformation and show that Death Domains can be used alone or as building blocks to engineer bioinspired hydrogels.

Mastigodiaptomus galapagoensis n. sp. (Crustacea: Copepoda: Diaptomidae), a possibly extinct copepod from a crater lake of the Galápagos archipelago.

Background: A new species of a Neotropical diaptomid copepod is described based on individuals recovered from a small, almost forgotten collection of unique plankton samples from El Junco, a crater lake in San Cristóbal island, Galápagos archipelago. This copepod was regularly reported (1966-2004) as an abundant zooplankter in the lake, but it was not found in subsequent plankton surveys (2007-2018), and its specific identity remained unknown. In 2020, it was declared extinct because of introduced fish predation, rotenone treatment, and other major disturbances. The taxonomic examination of these invaluable specimens allowed us to recognize them as representing an undescribed species of the freshwater diaptomid genus Mastigodiaptomus Light, 1939. Methods: Here, we describe the new species from El Junco crater lake, located in the San Cristóbal island a part of the Galápagos archipelago, collected with plankton nets. The description is based on detailed morphology, based on SEM and light microscopy. Results: The taxonomic examination of these invaluable specimens allowed us to recognize them as representing an undescribed species of the freshwater diaptomid genus Mastigodiaptomus Light, 1939. The new species was readily assigned to this genus and is distinguished from its known congeners by details of (1) the male right fifth leg terminal claw and aculeus, (2) spiniform processes pattern of the right geniculate antennule segments 10-16, (3) length and structure of the spiniform process of the antepenultimate segment of the male right antennule, and (4) details of the dorsal process on the female fourth pediger. This finding represents the first report of this Neotropical copepod genus outside its original biogeographic region, the third species of a diaptomid copepod reported from insular freshwater systems, the southernmost record of Mastigodiaptomus, and the only freshwater calanoid in the Galápagos. The intriguing presence of this chiefly Neotropical copepod genus here could be related either to (1) human agency linked to pirate activities, commercial travelling by Spaniard ships, whaling activities, and intense tortoise hunting in San Cristóbal island. In the past, El Junco was the only freshwater source 600 nautical miles around, or (2) zoochory of resistant dormant stages passively transported by more than 65 migrating bird species known to settle in San Cristóbal. These two hypotheses cannot be properly tested at this time, so the explanation of the presence of this copepod will remain as a new open question in the fascinating natural history of the Galápagos.

Effectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial.

BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.

Hopelessness in Patients with Early-Stage Relapsing-Remitting Multiple Sclerosis.

Background: Hopelessness is a risk factor for depression and suicide. There is little information on this phenomenon among patients with relapsing-remitting multiple sclerosis (RRMS), one of the most common causes of disability and loss of autonomy in young adults. The aim of this study was to assess state hopelessness and its associated factors in early-stage RRMS. Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The State-Trait Hopelessness Scale (STHS) was used to measure patients´ hopelessness. A battery of patient-reported and clinician-rated measurements was used to assess clinical status. A multivariate logistic regression analysis was conducted to determine the association between patients' characteristics and state hopelessness. Results: A total of 189 patients were included. Mean age (standard deviation-SD) was 36.1 (9.4) years and 71.4% were female. Median disease duration (interquartile range-IQR) was 1.4 (0.7, 2.1) years. Symptom severity and disability were low with a median EDSS (IQR) score of 1.0 (0, 2.0). A proportion of 65.6% (n=124) of patients reported moderate-to-severe hopelessness. Hopelessness was associated with older age (p=0.035), depressive symptoms (p=<0.001), a threatening illness perception (p=0.001), and psychological and cognitive barriers to workplace performance (p=0.029) in the multivariate analysis after adjustment for confounders. Conclusion: Hopelessness was a common phenomenon in early-stage RRMS, even in a population with low physical disability. Identifying factors associated with hopelessness may be critical for implementing preventive strategies helping patients to adapt to the new situation and cope with the disease in the long term.

Natural and engineered isoforms of the inflammasome adaptor ASC form non-covalent, pH-responsive hydrogels.

The protein ASC polymerizes into intricate filament networks to assemble the inflammasome, a filamentous multiprotein complex that triggers the inflammatory response. ASC carries two Death Domains integrally involved in protein self-association for filament assembly. We have leveraged this behavior to create non-covalent, pH-responsive hydrogels of full-length, folded ASC by carefully controlling the pH as a critical factor in the polymerization process. We show that natural variants of ASC (ASC isoforms) involved in inflammasome regulation also undergo hydrogelation. To further demonstrate this general capability, we engineered proteins inspired in the ASC structure that successfully form hydrogels. We analyzed the structural network of the natural and engineered protein hydrogels using transmission and scanning electron microscopy, and studied their viscoelastic behavior by shear rheology. Our results reveal one of the very few examples of hydrogels created by the self-assembly of globular proteins and domains in their native conformation and show that Death Domains can be used alone or as building blocks to engineer bioinspired hydrogels.

Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis.

Forces controlling tissue morphogenesis are attributed to cellular-driven activities, and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can develop autonomous stresses during their assembly. Here, we examine the morphogenetic function of an ECM before reaching homeostatic equilibrium by analyzing de novo ECM assembly during Drosophila ventral nerve cord (VNC) condensation. Asymmetric VNC shortening and a rapid decrease in surface area correlate with the exponential assembly of collagen IV (Col4) surrounding the tissue. Concomitantly, a transient developmentally induced Col4 gradient leads to coherent long-range flow of ECM, which equilibrates the Col4 network. Finite element analysis and perturbation of Col4 network formation through the generation of dominant Col4 mutations that affect assembly reveal that VNC morphodynamics is partially driven by a sudden increase in ECM-driven surface tension. These data suggest that ECM assembly stress and associated network instabilities can actively participate in tissue morphogenesis.

Assessment of Dentinal Tubules Penetration by Hyben X Delivered into the Root Canal System as an Irrigant; An in Vitro Study.

Introduction: Disinfection of the root canal system is crucial for a successful endodontic treatment. Several factors influence the performance of effective irrigation. Diverse irrigating substances have been used but none has proved to completely penetrate the root canal system. HybenX dries biofilm due to its hygroscopic properties; therefore, it is effective in the treatment of biofilm-related diseases. This investigation aimed to estimate HybenX's degree of penetration into the dentinal tubules of upper first premolars. Materials and Methods: Experimental in vitro intervention where 30 extracted maxillary premolars were evaluated to determine HybenX's degree of penetration and 5% sodium hypochlorite in the dentinal tubules using three different irrigation techniques (passive ultrasonic irrigation, dynamic manual irrigation and conventional single jet irrigation technique). After preparation, the root canals were irrigated with fluorescent rhodamine 6G; then 500-micrometer sections were made to be analyzed under a fluorescence microscope. Measurements were made in micrometer in ZEN software to determine the penetration degree of each substance in the different root thirds. Results: In the apical third, significant differences between the 3 irrigation techniques were found (P<0.05), similarly, for the middle and cervical thirds. Significant statistical differences between the HybenX and sodium hypochlorite were found at the cervical and middle levels when using the conventional Monoject irrigation and passive ultrasonic irrigation techniques. As for the apical level, differences were found between the passive ultrasonic irrigation techniques and the dynamic manual irrigation technique. Conclusions: Based on this in vitro study, HybenX proved to highly penetrate into the dentinal tubules, especially when using the passive ultrasonic irrigation technique. HybenX may be a useful option for root canal irrigation in endodontics.

Structuring of oils with high PUFA content: Evaluation of the formulation conditions on the oxidative stability and structural properties of ethylcellulose oleogels.

This study evaluated the formulation of ethylcellulose oleogels as a fat substitute, based on oils with a high content of polyunsaturated fatty acids. Optimal processing conditions for canola, linseed, and chia oil oleogels were determined. The results showed that the oxidative stability was affected to a greater extent in chia oil oleogel, however, the addition of BHT improved the oxidative stability, mainly the peroxide value. Linseed and chia oil oleogels with a high content of polyunsaturated fatty acids (64.28 and 73.02 g/100 g, respectively) were obtained despite the reduction of these with respect to their oils, and no trans fatty acids were produced. Chia oil oleogels were shown to exhibit similar physical properties to linseed oil oleogels in terms of firmness (463.51 ± 7.42 g and 443.03 ± 7.14 g respectively) and rheological behavior. Such a structure led to a dominant elastic character of the oleogels to mimic the mechanical properties of animal fat.

Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics.

Introduction: Mild cognitive impairment (MCI) can progress to Alzheimer's disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI. Methods: In this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies. Results: Fifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points). Conclusion: The results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05029765].