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Objective: Oral cancer examinations seek to clinically identify early oral cancers and discover premalignancies prior to their progression to invasive cancer., Method and Materials: A cross-sectional study was conducted between April and August 2017 to explore and quantify the diagnostic approach used by United States (US) general dental practitioners following discovery of an oral lesion suspicious for malignancy/premalignancy. US licensed general dental practitioners who were clinically active members of the US National Dental Practice-Based Research Network were eligible to participate. Data for analysis were obtained via two questionnaires., Results: The majority of participants were males, practiced full-time, had a suburban primary practice, were born during the 1950s, and graduated dental school in the 1980s or 2000s. After identifying an oral lesion suspicious for premalignancy/malignancy, the next action of most general dental practitioner respondents (65.4%) was to refer the patient for consultation/biopsy. Most general dental practitioners (87.2%) referred to an oral and maxillofacial surgeon; 22% of general dental practitioners reported personally biopsying suspicious lesions. There was a relatively weak association between completing an Advanced Education in General Dentistry or General Practice Residency and subsequently personally performing biopsies on patients with oral lesions suspicious for malignancy/premalignancy (OR 1.33, P = .06). Most written referrals took place electronically and often included information, including lesion location (87.0%), lesion sign/symptoms (85.3%), lesion history (83.9%), radiographs (59.3%), medical history (50.6%), dental history (48.8%), and photographs (42.4%). When a referral biopsy was performed, referring clinicians were most frequently informed of the findings via a written report (96.7%, when positive for malignancy/premalignancy, and 95.4% when negative)., Conclusion: A snapshot is presented of current actions taken by US general dental practitioners following the discovery of oral abnormalities suspicious for premalignancy/malignancy.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

The objective of this study was to evaluate the possible use of spectrophotometric assays for the measurement of trace elements, including Zinc (Zn), Copper (Cu), Magnesium (Mg), and iron (Fe) in the saliva of horses and study their possible changes in equine gastric ulcer syndrome (EGUS). EGUS is a highly prevalent disease, with a current high incidence due to the increase in intensive management conditions. There are two EGUS diseases: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), which can appear individually or together. For this purpose, automated spectrophotometric assays for measuring these analytes in horse saliva were analytically validated. Then, these analytes were measured in the saliva of horses with only ESGD, only EGGD, both ESGD and EGGD and a group of healthy horses. The methods used to measure the analytes were precise and accurate. Horses diagnosed with EGGD presented significantly lower levels of Zn and Mg. Fe concentrations were significantly lower in the saliva of horses with ESGD and EGGD. Overall, these results indicate that there are changes in trace elements in saliva in EGUS that could reflect the physiopathological mechanisms involved in this process and open the possibility of using trace elements as biomarkers of this syndrome.

Introduction: Stress, described as an adaptation of the body to an event, is a considerable problem among health workers, especially for those who work in emergency situations, as they very often have to face complex situations. It has been proven that stress affects the performance of health professionals, which is why it is interesting to measure it in these situations, to be able to know what methods to implement to reduce it in future events. Despite having previous measurements in healthcare personnel during clinical simulations, this study is relevant because stress has never before been measured in EMS professionals when performing their work., Objective: To determine the acute stress experienced by professionals in an Emergency Medical Service (EMS) when handling five types of clinical emergencies. As secondary objectives, to determine if there were differences in the increases in stress in relation to sex, age, profession, team, and above all, type of emergency handled., Method: The following were measured for the analysis: physiological (mean heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure), and biochemical (salivary alpha amylase (sAA) activity) markers, before (Basal) and after (Post-Stress) the interventions of 27 professionals from an EMS., Results: In general, the results obtained showed significant differences between the baseline measurement of physiological and biochemical markers versus the post-exposure measurement. Some of the differences in stress levels in relation to sex and professional role are striking., Conclusion: The determination of acute stress experienced by professionals from an EMS in a real emergency showed significant increases in the sAA enzymatic marker of acute stress. These results are the first data published in this regard, and could be used as a reference to follow in clinical simulation in the training of students and the training of nursing professionals., Implications for Clinical Practice: Evidence based studies are needed to improve the education and training of emergency and intensive care professionals. The results from are a great step in the analysis of the real stress that professionals are subjected to when they handle different emergencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Paired sets and alternative set configurations (e.g., cluster sets) are frequently employed by strength and conditioning practitioners; however, their synergistic impact remains underexplored in research. This study aimed to elucidate whether the set configuration used in a lower-body exercise affects mechanical performance during paired sets of upper-body exercises., Methods: Twenty-one resistance-trained individuals (14 men and 7 women) randomly completed three experimental sessions that involved four sets of five repetitions at 75%1RM during both the bench press and bench pull exercises. The three experimental sessions varied solely in the activity conducted during the inter-set rest periods of each upper-body exercise: (i) Traditional squat - six squat repetitions without intra-set rest at 65%1RM; (ii) Rest redistribution squat - two clusters of three repetitions of the squat exercise at 65%1RM with 30 s of intra-set rest; and (iii) Passive rest - no exercise., Results: The rest redistribution set configuration allowed the sets of the squat exercise to be performed at a faster velocity than the traditional set configuration (p = 0.037). However, none of the mechanical variables differed between the exercise protocols neither in the bench press (p ranged from 0.279 to 0.875) nor in the bench pull (p ranged from 0.166 to 0.478)., Conclusions: Although rest redistribution is an effective strategy to alleviate fatigue during the sets in which it is implemented, it does not allow subjects to perform better in subsequent sets of the training session., (© 2024. The Author(s).)

Exposure to stress induced by intermittent repeated social defeat (IRSD) increases vulnerability to the development of cocaine-induced conditioned place preference (CPP) among male mice; however, some defeated mice are resilient to these effects of stress. In the present study we evaluated the effects of vicarious IRSD (VIRSD) in female mice and explored behavioural traits that are potentially predictive of resilience. C57BL/6 female mice (n = 28) were exposed to VIRSD, which consisted of the animals witnessing a short experience of social defeat by a male mouse on postnatal day (PND) 47, 50, 53 and 56. The control group (n = 10) was not exposed to stress. Blood samples were collected on PND 47 and 56 for corticosterone and interleukin-6 determinations. On PND 57-58, female mice performed several behavioural tests (elevated plus maze, hole-board, object recognition, social interaction, TST and splash tests). Three weeks later, the effects of cocaine (1.5 mg/kg) on the CPP paradigm were assessed. VIRSD decreased corticosterone levels (on PND 56), increased interleukin-6 levels, enhanced novelty-seeking, improved recognition memory and induced anxiety- and depression-like symptoms. Control and VIRSD female mice did not acquire CPP, although some stressed individuals with certain behavioural traits - including a high novelty-seeking profile or the development of depression-like behaviour in the splash test shortly after VIRSD - acquired cocaine CPP. Our results confirm that some behavioural traits of female mice are associated with vulnerability or resilience to the long-term effects of social stress on cocaine reward, as previously observed in males., Competing Interests: Declaration of Competing Interest All the authors declare no financial/personal interest that could affect the objectivity of their work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Information on the performance of oxygenation indices (OIs) and risk scores in patients requiring invasive mechanical ventilation (IMV) is limited. We determine the performance of the OIs and risk scores in hospitalized patients with COVID-19 to predict the requirement of IMV and death at 28 days after admission., Methods: A retrospective study of diagnostic tests in patients admitted to the emergency department, hospitalization, and intensive care unit diagnosed with COVID-19. The receiver operating characteristic curve (ROC-curve) were built with the OIs and risk scores to predict IMV and mortality., Results: A total of 1402 subjects entered the final analysis, of whom 19.5% (274/1402) received IMV and 23.0% (323/1402) died at 28 days. The ROC-curve of the delta PaO2/FiO2 ratio for the requirement of IMV and mortality at 28-day was 0.589 (95% CI: 0.546-0.632) and 0.567 (95% CI: 0.526-0.608), respectively. PaO2/FiO2 ≤ 300 shows a ROC curve of 0.669 (95% CI: 0.628-0.711) to predict IMV. PaO2/FiO2 ≤ 300 and 4 C mortality score in mortality at 28 days showed an ROC-curve of 0.624 (95% CI: 0.582-0.667) and 0.706 (95% CI: 0.669-0.742), respectively., Conclusion: PaO2/FiO2 ≤ 300, 4 C mortality score ≥ 8, SOFA score ≥ 4 y SaO2/FiO2 ≤ 300 were weak predictors of the IMV requirement from admission, and 4 C mortality score ≥ 8 was weak predictors of the mortality from admission in patients with pulmonary involvement by COVID-19., (© 2024. The Author(s).)

This study aimed to explore whether the relationship between perceptual (rating of perceived exertion; RPE) and mechanical (maximal number of repetitions completed [MNR], fastest set velocity, and mean velocity decline) variables is affected by the length of inter-set rest periods during resistance training sets not leading to failure. Twenty-three physically active individuals (15 men and eight women) randomly completed 12 testing sessions resulting from the combination of two exercises (bench press and bench pull), three inter-set rest protocols (1, 3, and 5 min), and two minimal velocity thresholds (farther from muscular failure [MVT 0.45 for bench press and MVT 0.65 for bench pull] and closer to muscular failure [MVT 0.35 for bench press and MVT 0.55 for bench pull]). The duration of inter-set rest periods did not have a significant impact on RPE values ( p ranged from 0.061 to 0.951). Higher proximities to failure, indicated by lower MVTs, were associated with increased RPE values ( p < 0.05 in 19 out of 24 comparisons). Moreover, as the number of sets increased, an upward trend in RPE values was observed ( p < 0.05 in seven out of 12 comparisons). Finally, while acknowledging some inconsistencies, it was generally observed that higher magnitudes of the mechanical variables, especially MNR ( r s < -0.55 in three out of four comparisons), were associated with lower RPE values. These results, which were comparable for the bench press and bench pull exercises, suggest that post-set RPE values are affected by the fatigue experienced at both the beginning and end of the set., Competing Interests: Amador García-Ramos is an Academic Editor for PeerJ., (© 2024 Janicijevic et al.)

This study examined the influence of inter-set rest periods of 1 (R1), 3 (R3) and 5 (R5) minutes on the number of repetitions completed before exceeding the minimum velocity thresholds of 0.45 m⋅s -1 (MVT 0.45 ) and 0.35 m⋅s -1 (MVT 0.35 ) during the bench press exercise. Twenty-three physically active individuals, 15 men and eight women, randomly completed six testing sessions consisting of four sets of the bench press exercise performed with maximal intent against 75% of the one-repetition maximum. Testing sessions differed in the length of inter-set rest periods (R1, R3, and R5) and MVT applied (MVT 0.45 and MVT 0.35 ). The number of repetitions was lower using shorter inter-set rest periods (R1 < R3 < R5), but R3 was more similar to R1 and R5 using MVT 0.45 and MVT 0.35 , respectively. The fastest velocity of the set was reduced with the increment in the number of sets for the three protocols using MVT 0.35 (greater reduction for shorter rest periods), but it was only reduced for R1 when using MVT 0.45 . The results suggest that, to maintain bench press mechanical performance, 5-min inter-set rest periods are necessary when sets are terminated close to failure (MVT 0.35 ), while 3 min may suffice when sets are terminated farther from failure (MVT 0.45 ).

Context: Current devices to assess strength performance in handball may not be sufficiently sports-specific and reliable methods. Functional electromechanical dynamometry is a new technology that allows the development of accurate strength tests in athletes., Purpose: To determine the absolute and relative reliability and to compare the reliability of the right and left side, and mean and peak force of 3 specific strength tests in handball players with a functional electromechanical dynamometer: unilateral pullover, standing lift, and step forward., Methods: Fourteen male handball players of the first Spanish division (28.79 [4.81] y; 10.38 [4.63] y of professional experience) performed a repeated-measurement design. Three testing sessions were performed (one per week). The first measurement consisted of 4 isometric tests (right and left unilateral pullover, and right and left standing lift) to obtain isometric peak force, and in the second and third sessions, 6 incremental tests until failure (right and left unilateral pullover, and right and left standing lift, right and left step forward) were performed., Results: The tests provided high reliability or acceptable reliability for mean and peak strength of unilateral pullover, standing lift and step forward (intraclass correlation coefficient = .83-.97; coefficient of variation = 3.90-11.57). Effect side was negligible in any of the parameters, except for a small effect side in the left peak force for unilateral pullover and a small effect side on the left side for a step forward. Significant differences in reliability (coefficient of variation ratio > 1.15) were found between the right and left sides and peak and mean force in all exercises except peak force in unilateral pullover and step forward., Conclusion: These results confirm that the tests could be applied to assess physical performance in handball at the same time as regular gym training. Moreover, this is an excellent opportunity to individualize the player's weekly load.

High hydrostatic pressure (HHP) is a non-thermal process widely used in the food industry to reduce microbial populations. However, rarely its effect has been assessed in products with high oil content. This study evaluated the efficacy of HHP (200, 250, and 300 MPa) at different temperatures (25, 35, and 45 °C) by cycles (1, 2, or 3) of 10 min in the inactivation of Aspergillus niger spores in a lipid emulsion. After treatments at 300 MPa for 1 cycle at 35 or 45 °C, no surviving spores were recovered. All treatments were modeled by the linear and Weibull models. The presence of shoulders and tails in the treatments at 300 MPa at 35 or 45 °C resulted in sigmoidal curves which cannot be described by the linear model, hence the Weibull + Tail, Shoulder + Log-lin + Tail, and double Weibull models were evaluated to elucidate the inactivation kinetics. The tailing formation could be related to the presence of resistance subpopulations. The double Weibull model showed better goodness of fit (RMSE <0.2) to describe the inactivation kinetics of the treatments with the higher spore reductions. HHP at 200-300 MPa and 25 °C did not reduce the Aspergillus niger spores. The combined HHP and mild temperatures (35-45 °C) favored fungal spore inactivation. Spore inactivation in lipid emulsions by HHP did not follow a linear inactivation. HHP at mild temperatures is an alternative to the thermal process in lipid emulsions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: Janicijevic, D, Pérez-Castilla, A, Miras-Moreno, S, Ortega-Becerra, M, Morenas-Aguilar, MD, Smajla, D, Sarabon, N, and García-Ramos, A. Effect of a high-intensity handball-specific fatigue protocol focused on the leg contralateral to the throwing arm on interlimb asymmetries. J Strength Cond Res 37(7): 1382-1389, 2023-This study aimed to elucidate which countermovement jump (CMJ) variant (unilateral or bilateral) is more sensitive to detect the decrement in kinetic CMJ-derived variables of the leg more actively involved in a handball-specific fatigue protocol. Seventeen female handball players (age: 20.6 ± 2.5 years) performed a fatigue protocol consisting of 8 repetitions of the following circuit separated by 10 seconds: 10 m sprint, 180° change of direction with the leg contralateral to the throwing arm, 10 m sprint with ball reception at 7 m, and handball throw preceded by a jump over a 40 cm hurdle with the leg contralateral to the throwing arm. Before and after the fatigue protocol, 6 unilateral CMJs (3 with each leg) and 3 bilateral CMJs were performed on a dual Kistler force platform (model 9260AA6). Bilateral CMJ height was reduced by 5.4% after the fatigue protocol (p < 0.001). However, the fatigue protocol did not promote any significant change in peak force, mean force, and propulsive impulse or in their asymmetry values (17 of 18 comparisons). The decrement of 6.1% during the unilateral CMJ in the propulsive impulse developed by the leg ipsilateral to the throwing arm (less involved in the fatigue protocol) was the only variable that reached statistical significance (p = 0.038). The pre-post fatigue changes in asymmetry values presented negligible correlations between both CMJ variants (rs = 0.01 to -0.19). These results suggest that neither unilateral nor bilateral CMJs are able to detect changes in interlimb asymmetries after a high-intensity handball-specific fatigue protocol., (Copyright © 2022 National Strength and Conditioning Association.)

One of the biggest challenges in developing effective therapies against glioblastoma is overcoming the strong immune suppression within the tumor microenvironment. Immunotherapy has emerged as an effective strategy to turn the immune system response against tumor cells. Glioma-associated macrophages and microglia (GAMs) are major drivers of such anti-inflammatory scenarios. Therefore, enhancing the anti-cancerous response in GAMs may represent a potential co-adjuvant therapy to treat glioblastoma patients. In that vein, fungal β-glucan molecules have long been known as potent immune modulators. Their ability to stimulate the innate immune activity and improve treatment response has been described. Those modulating features are partly attributed to their ability to bind to pattern recognition receptors, which, interestingly, are greatly expressed in GAMs. Thus, this work is focused on the isolation, purification, and subsequent use of fungal β-glucans to enhance the tumoricidal response of microglia against glioblastoma cells. The mouse glioblastoma (GL261) and microglia (BV-2) cell lines are used to test the immunomodulatory properties of four different fungal β-glucans extracted from mushrooms heavily used in the current biopharmaceutical industry: Pleurotus ostreatus, Pleurotus djamor, Hericium erinaceus, and Ganoderma lucidum. To test these compounds, co-stimulation assays were performed to measure the effect of a pre-activated microglia-conditioned medium on the proliferation and apoptosis activation in glioblastoma cells.

Background: Exposure to intermittent repeated social defeat (IRSD) increases the sensitivity of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. Some animals are resilient to this effect of IRSD, though research exploring this inconsistency in adolescent mice is scarce. Thus, our aim was to characterize the behavioral profile of mice exposed to IRSD during early adolescence and to explore a potential association with resilience to the short- and long-term effects of IRSD., Methods: Thirty-six male C57BL/6 mice were exposed to IRSD during early adolescence (PND 27, 30, 33 and 36), while another 10 male mice did not undergo stress (controls). Defeated mice and controls then carried out the following battery of behavioral tests; the Elevated Plus Maze, Hole-Board and Social Interaction Test on PND 37, and the Tail Suspension and Splash tests on PND 38. Three weeks later, all the mice were submitted to the CPP paradigm with a low dose of cocaine (1.5 mg/kg)., Results: IRSD during early adolescence induced depressive-like behavior in the Social Interaction and Splash tests and increased the rewarding effects of cocaine. Mice with low levels of submissive behavior during episodes of defeat were resilient to the short- and long-term effects of IRSD. In addition, resilience to the short-term effects of IRSD on social interaction and grooming behavior predicted resilience to the long-term effects of IRSD on cocaine reward., Conclusion: Our findings help to characterize the nature of resilience to the effects of social stress during adolescence., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Premise: Habitat fragmentation negatively affects population size and mating patterns that directly affect progeny fitness and genetic diversity; however, little is known about the effects of habitat fragmentation on dioecious, wind pollinated trees. We assessed the effects of habitat fragmentation on population sex ratios, genetic diversity, gene flow, mating patterns, and early progeny vigor in the tropical dioecious tree, Brosimum alicastrum., Methods: We conducted our study in three continuous and three fragmented forest sites in a Mexican tropical dry forest. We used eight microsatellite loci to characterize the genetic diversity, gene flow via pollen distances, and mean relatedness of progeny. We compared early progeny vigor parameters of seedlings growing under greenhouse conditions., Results: Sex ratios did not deviate from 1:1 between habitat conditions except for one population in a fragmented habitat, which was female biased. The genetic diversity of adult trees and their offspring was similar in both habitat conditions. Pollen gene flow distances were similar across habitat types; however, paternity correlations were greater in fragmented than in continuous habitats. Germination rates did not differ between habitat conditions; however, progeny from fragmented habitats produced fewer leaves and had a lower foliar area, total height, and total dry biomass than progeny from continuous habitats., Conclusions: Changes in mating patterns because of habitat fragmentation have negative effects on early progeny vigor. We conclude that negative habitat fragmentation effects on mating patterns and early progeny vigor may be a serious threat to the long-term persistence of tropical dioecious trees., (© 2023 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Current limitations of wound dressings for treating chronic wounds require the development of novel approaches. One of these is the immune-centered approach, which aims to restore the pro-regenerative and anti-inflammatory properties of macrophages. Under inflammatory conditions, ketoprofen nanoparticles (KT NPs) can reduce pro-inflammatory markers of macrophages and increase anti-inflammatory cytokines. To assess their suitability as part of wound dressings, these NPs were combined with hyaluronan (HA)/collagen-based hydro- (HGs) and cryogels (CGs). Different HA and NP concentrations and loading techniques for NP incorporation were used. The NP release, gel morphology, and mechanical properties were studied. Generally, colonialization of the gels with macrophages resulted in high cell viability and proliferation. Furthermore, direct contact of the NPs to the cells reduced the level of nitric oxide (NO). The formation of multinucleated cells on the gels was low and further decreased by the NPs. For the HGs that produced the highest reduction in NO, extended ELISA studies showed reduced levels of the pro-inflammatory markers PGE2, IL-12 p40, TNF-α, and IL-6. Thus, HA/collagen-based gels containing KT NPs may represent a novel therapeutic approach for treating chronic wounds. Whether effects observed in vitro translate into a favorable profile on skin regeneration in vivo will require rigorous testing.

Background: The septate uterus is the most common congenital uterine anomaly, and hysteroscopy is the gold standard for diagnosing it. The goal of this meta-analysis is to perform a pooled analysis of the diagnostic performance of two-dimensional transvaginal ultrasonography, two-dimensional transvaginal sonohysterography, three-dimensional transvaginal ultrasound, and three-dimensional transvaginal sonohysterography for the diagnosis of the septate uterus., Methods: Studies published between 1990 and 2022 were searched in PubMed, Scopus, and Web of Science. From 897 citations, we selected eighteen studies to include in this meta-analysis., Results: The mean prevalence of uterine septum in this meta-analysis was 27.8%. Pooled sensitivity and specificity were 83% and 99% for two-dimensional transvaginal ultrasonography (ten studies), 94% and 100% for two-dimensional transvaginal sonohysterography (eight studies), and 98% and 100% for three-dimensional transvaginal ultrasound (seven articles), respectively. The diagnostic accuracy of three-dimensional transvaginal sonohysterography was only described in two studies, and we did not calculate the pooled sensitivity and specificity for this method., Conclusion: Three-dimensional transvaginal ultrasound has the best performance capacity for the diagnosis of the septate uterus.

This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups onto the Cs backbone (Cs-DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution [DS (%)] was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs-DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC 50 ). An EC 50 of 1.20 μg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan-catechol (Cs-Ca) and Cs-DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 μg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs-DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 μg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter ( D h ) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.

Skin is the most extensive organ within our body. It is continually subjected to stress factors, among which ultraviolet irradiation, a key factor responsible in skin aging since it leads to reactive oxygen species production. In order to fight against these oxidative species, the human body has an innate robust antioxidant mechanism composed of several different substances, one of which is coenzyme Q 10 . Its capacity to increase cellular energy production and excellent antioxidant properties have been proved, as well as its antiaging properties being able to attenuate cellular damage induced by ultraviolet irradiation in human dermal fibroblasts. However, its high hydrophobicity and photolability hampers its therapeutic potential. In this context, the objective of this work consists of the preparation of chitosan-rosmarinic acid conjugate-based nanoparticles to encapsulate coenzyme Q10 with high encapsulation efficiencies in order to improve its bioavailability and broaden its therapeutic use in skin applications. Hyaluronic acid coating was performed giving stable nanoparticles at physiological pH with 382 ± 3 nm of hydrodynamic diameter (0.04 ± 0.02 polydispersity) and - 18 ± 3 mV of surface charge. Release kinetics studies showed a maximum of 82 % mass release of coenzyme Q 10 after 40 min, and radical scavenger activity assay confirmed the antioxidant character of chitosan-rosmarinic acid nanoparticles. Hyaluronic acid-coated chitosan-rosmarinic acid nanoparticles loaded with coenzyme Q 10 were biocompatible in human dermal fibroblasts and exhibited interesting photoprotective properties in ultraviolet irradiated cells. In addition, nanoparticles hindered the production of reactive oxygen species, interleukin-6 and metalloproteinase-1, as well as caspase-9 activation maintaining high viability values upon irradiation of dermal fibroblasts. Overall results envision a great potential of these nanovehicles for application in skin disorders or antiaging treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Articular cartilage is an avascular tissue that lines the ends of bones in diarthrodial joints, serves as support, acts as a shock absorber, and facilitates joint's motion. It is formed by chondrocytes immersed in a dense extracellular matrix (principally composed of aggrecan linked to hyaluronic acid long chains). Damage to this tissue is usually associated with traumatic injuries or age-associated processes that often lead to discomfort, pain and disability in our aging society. Currently, there are few surgical alternatives to treat cartilage damage: the most commonly used is the microfracture procedure, but others include limited grafting or alternative chondrocyte implantation techniques, however, none of them completely restore a fully functional cartilage. Here we present the development of hydrogels based on hyaluronic acid and chitosan loaded with chondroitin sulfate by a new strategy of synthesis using biodegradable di-isocyanates to obtain an interpenetrated network of chitosan and hyaluronic acid for cartilage repair. These scaffolds act as delivery systems for the chondroitin sulfate and present mucoadhesive properties, which stabilizes the clot of microfracture procedures and promotes superficial chondrocyte differentiation favoring a true articular cellular colonization of the cartilage. This double feature potentially improves the microfracture technique and it will allow the development of next-generation therapies against articular cartilage damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Escalante, Rico, Becerra, San Román, Vázquez-Lasa, Aguilar, Durán and García-Fernández.)

During the pandemic, the elderly population was the most exposed to disease and changes in their daily lives. The objective was to determine the association between demographic factors, access to health services, sources of information, and physical symptoms in the mental health of the elderly during the COVID-19 pandemic-a study with 3828 older adults residing in nine cities in Peru. The data was collected using a web-based survey, and the instruments of demographic data; exposure to information (radio, television, and internet); and presence of physical symptoms, anxiety, and perceived stress were used. Descriptive and analytical analysis was performed. Female sex, those aged between 60 and 79 years old, those with secondary education, those in their own home, those residing in an urban area, and those using public services of health predominated in this study. Likewise, 62.9% presented depressive symptoms; on the stress scale, an average of 27.81 (SD = 8.71), and on the anxiety scale, an average of 27.24 (SD = 6.04). Moreover, 65.1% reported fatigue, 62.2% had a headache, and 61.2% lack of energy. There is an association between demographic variables and the physical and psychological symptoms of stress, anxiety, and depressive symptoms in the elderly during the pandemic.

Changes in the salivary proteome in 12 horses with the two diseases included in equine gastric ulcer syndrome (EGUS), equine glandular gastric disease (EGGD) ( n = 6) and equine squamous gastric disease (ESGD) ( n = 6), were evaluated using a high-resolution LC-MS/MS analysis of TMT-labelled peptides and compared to 10 healthy control horses. Serum was also analysed for comparative purposes. The comparison between the horses with EGGD and controls showed significant changes in 10 salivary proteins, whereas 36 salivary proteins were differently abundant between ESGD and control groups. The most upregulated proteins in the case of EGGD were related to immune activation whereas, in horses with ESGD, the most significantly changed proteins were associated with squamous cell regulation and growth. Compared to serum, saliva showed a higher number of proteins with significant changes and a different pattern of changes. The proteins identified in our study, in addition to providing new information about the pathophysiological mechanisms in these diseases, could have the potential to be novel biomarkers for the diagnosis or monitoring of EGGD and ESGD.

Background: The pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group., Methods: A double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group., Results: There were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention., Conclusion: Spanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03620097]., Competing Interests: MO was a worker of Biosearch Life, a company that marketed the placebo and the nutritional supplement, EUPOLY-3 DHA® Infant, following the regulations of the European Union. These supplements were provided free of charge by Biosearch SA (Granada, Spain). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de la Torre-Aguilar, Gomez-Fernandez, Flores-Rojas, Martin-Borreguero, Mesa, Perez-Navero, Olivares, Gil and Gil-Campos.)

Background: Efficacy of telemedicine for stroke was first established by the Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trials in California and Arizona. Following these randomized controlled trials, the Stroke Telemedicine for Arizona Rural Residents (STARR) network was the first telestroke network to be established in Arizona. It consisted of a 7 spoke 1 hub telestroke system, and it was designed to serve rural, remote, or neurologically underserved communities., Objective: The objective of STARR was to establish a multicenter state-wide telestroke research network to determine the feasibility of prospective collection, recording, and regularly analysis of telestroke patient consultations and care data for the purposes of establishing quality measures, improvement, and benchmarking against other national and international telestroke programs., Methods: The STARR trial was open to enrollment for 29 months from 2008 to 2011. Mayo Clinic Hospital, Phoenix, Arizona served as the hub primary stroke center and its vascular neurologists provided emergency telestroke consultations to seven participating rural, remote, or underserved spoke community hospitals in Arizona. Eligibility criteria for activation of a telestroke alert and study enrollment were established. Consecutive patients exhibiting symptoms and signs of acute stroke within a 12 h window were enrolled, assessed, and treated by telemedicine. The state government sponsor, Arizona Department of Health Services' research grant covered the cost of acquisition, maintenance, and service of the selected telemedicine equipment as well as the professional telestroke services provided. The study deployed multiple telemedicine video cart systems, picture archive and communications systems software, and call management solutions. The STARR protocol was reviewed and approved by Mayo Clinic IRB, which served as the central IRB of record for all the participating hospitals, and the trial was registered at ClinicalTrials.gov., Results: The telestroke hotline was activated 537 times, and ultimately 443 subjects met criteria and consented to participate. The STARR successfully established a multicenter state-wide telestroke research network. The STARR developed a feasible and pragmatic approach to the prospective collection, storage, and analysis of telestroke patient consultations and care data for the purposes of establishing quality measures and tracking improvement. STARR benchmarked well against other national and international telestroke programs. STARR helped set the foundation for multiple regional and state telestroke networks and ultimately evolved into a national telestroke network., Conclusions: Multiple small and rurally located community hospitals and health systems can successfully collaborate with a more centrally located larger hospital center through telemedicine technologies to develop a coordinated approach to the assessment, diagnosis, and emergency treatment of patients manifesting symptoms and signs of an acute stroke syndrome. This model may serve well the needs of patients presenting with other time-sensitive medical emergencies.Clinical Trial Registration number: NCT00829361., Competing Interests: No competing financial interests exist., (© Bart M. Demaerschalk et al., 2022; Published by Mary Ann Liebert, Inc.)

A career in journalism can be very stressful, as journalists frequently have to deal with uncontrolled situations such as conducting live interviews. Therefore, training is essential during their career, both for the development of communication skills and for the improvement of the real and effective capacity to perform the tasks of their professional activity. The aim of this study was to assess the levels of stress in students before and after a practical training in a professional television set using subjective (State-Trait Anxiety Inventory (STAI) and Likert scale) and objective (salivary cortisol and alpha-amylase) methods. The results indicate that a live interview produces stress in the students as revealed by increased concentrations of cortisol and alpha amylase in saliva. Furthermore, students with lower initial concentrations of these biomarkers obtained better grades in evaluation, suggesting that greater control of anticipatory stress could be associated with a better activity performance.

We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of abuse. We define the concept of resilience and how it is applied to the field of drug addiction research. We also describe the internal and external protective factors associated with resilience, such as individual behavioral traits and social support. We then explain the physiological response to stress and how it is modulated by resilience factors. In the subsequent section, we describe the animal models commonly used in the study of resilience to social stress, and we focus on the effects of chronic social defeat (SD), a kind of stress induced by repeated experience of defeat in an agonistic encounter, on different animal behaviors (depression- and anxiety-like behavior, cognitive impairment and addiction-like symptoms). We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depression- and anxiety-related behaviors in rodents. Finally, we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse, describing the current state of knowledge and suggesting future research directions., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cocaine use disorder is a serious problem worldwide, and there are no approved medications for its treatment. A novel approach to the treatment of drug addiction is the use of natural products, and, in this context, preclinical evidence suggests that Hypericum perforatum L. (Hypericum) is effective against alcohol and other substance use disorders. We hypothesised that Hypericum could also be useful as a treatment for cocaine use disorder, and so we set out to test its effectiveness in a mice model of cocaine addiction. In the first experiment we evaluated its effects on the acquisition of cocaine-induced conditioned place preference (CPP). Adult male mice were conditioned with cocaine (25 mg/kg), cocaine with Hypericum (75, 150 or 300 mg/kg) or the plant extract alone (300 mg/kg). In the second experiment, we tested the effects of Hypericum on stress-induced reinstatement of cocaine CPP. All the mice were conditioned with cocaine (25 mg/kg) and, after extinction of CPP, the reinstating effects of social defeat (alone or with 75, 150 or 300 mg/kg of Hypericum) were evaluated. All the doses of Hypericum prevented the acquisition of cocaine-induced CPP. Furthermore, the plant extract dose-dependently reduced the reinstating effects of social defeat. Therefore, Hypericum is effective in reducing the rewarding effects of cocaine and prevents the stress-induced reinstatement of cocaine CPP in mice. The mechanisms underlying these positive effects of Hypericum perforatum L. need to be determined by future research. Our results endorse Hypericum as a natural treatment for cocaine dependence., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO 3 - in extracellular solutions used to record slow waves indicates a role for HCO 3 - transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na + /HCO 3 - cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO 3 - concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects., Methods: Immunohistochemistry and sharp electrode electrical recordings were used., Key Results: The NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO 3 - from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow-wave amplitude and frequency. In 100 mM HCO 3 - , the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na + with Li + , an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO 3 - . There were no additional changes to electrical activity when HCO 3 - was removed from Li + containing solutions. The Na + /HCO 3 - cotransport inhibitor, S-0859 (30µM) significantly reduced the effect of removing HCO 3 - on electrical activity., Conclusions & Inferences: These studies demonstrate a major role for Na + /HCO 3 - cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract., (© 2021 John Wiley & Sons Ltd.)

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as female. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

Background: The effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well known. This work was aimed to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus (T2DM) hospitalized for COVID-19., Method: We conducted a nationwide, multicenter, observational study in patients ≥80 years with T2DM hospitalized for COVID-19 between March 1 and May 29, 2020. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis was performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality., Results: Of the 2 763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (adjusted odds ratio [AOR] 0.502, 95% confidence interval [CI]: 0.309-0.815, p = .005) and angiotensin receptor blockers (AOR 0.454, 95% CI: 0.274-0.759, p = .003) were independent protectors against in-hospital mortality, whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95% CI: 1.092-2.842, p = .020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins showed neutral association with in-hospital mortality., Conclusions: We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with T2DM hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders., Aims: This work aims to evaluate the ability of CBD to reduce priming- and stress-induced reinstatement of the conditioned place preference (CPP) induced by cocaine., Methods: Young adult CD-1 male mice were allocated to 10 groups ( n = 12/group), conditioned with cocaine (10 mg/kg) and exposed to extinction of CPP (two sessions per week). When extinction was achieved, each group received the corresponding treatment before the reinstatement test. In experiment 1, six groups were used: vehicle+saline (Veh+Sal), 5 mg/kg cocaine alone (Veh+Coc) or with CBD 30 or 60 mg/kg (CBD30+Coc, CBD60+Coc) and CBD alone (CBD30+Sal, CBD60+Sal). In experiment 2, four groups were used: exploration (Veh+Expl), social defeat (Veh+SD) and social defeat with CBD (CBD30+SD and CBD60+SD). Furthermore, the relative gene expression of the dopamine transporter (DAT) in the ventral tegmental area was measured., Results: All mice acquired cocaine CPP and extinguished it after three or four weeks. Only the groups treated with cocaine priming (Veh+Coc) or exposed to social defeat (Veh+SD) showed reinstatement of CPP. Interestingly, CBD itself did not induce reinstatement and blocked the reinstating effects of cocaine priming and social defeat. Furthermore, cocaine priming increased DAT gene expression in the ventral tegmental area and CBD completely reversed this effect., Conclusion: These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.

Introduction: Over the past decades, incidence of SLE (Systemic Lupus Erythematosus) has increased due to early case detection and improved survival of patients. SLE presents at an earlier age and has a more severe presentation in African-American, Native American, Asian, and Hispanic populations. Worldwide, lupus nephritis (LN) is observed in 29-60% of SLE patients, it has a negative impact in renal survival and patient mortality. Several cohorts have established potential risk factors associated with lupus nephritis, such as male sex, serological markers, and some extra-renal manifestations., Objectives: To describe sociodemographic, clinical, immunological, and environmental risk factors in Colombian SLE patients and to compare the population with and without nephritis, in order to establish risk factors and possible associations., Materials and Methods: A total of 1175 SLE patients participated in this study. During medical care, an interview and structured survey was conducted and later registered in a database. Sociodemographic, clinical, immunological, and environmental exposure variables were analyzed. Bivariate and multivariate analyses were performed using presence of LN as an outcome., Results: Prevalence of LN was 38.7%. Variables significantly associated with LN included being male (OR 1.98), a duration of SLE>10 years (OR 1.48), positive anti-DNA (OR 1.34), positive anti-Sm (OR 1.45), and smoking (OR 1.66). Being non-smoker was a protective factor (OR 0.52)., Conclusion: This study describes potential factors associated with lupus nephritis in a Latin American population. Smoking status could be a target for intervention as it is a modifiable risk factor. The association between being male and LN is observed in Latin-American populations such as presented here. Further research in other large-scale population studies and more efforts are needed to gain better insights to explicate these relationships., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Cytotoxic chemotherapy continues to be the main therapeutic option for patients with metastatic breast cancer. Several studies have reported a significant association between chronic inflammation, carcinogenesis and the presence of cancer stem cells (CSC). We hypothesized that the use of non-steroidal anti-inflammatory drugs targeted to the CSC population could help reducing tumor progression and dissemination in otherwise hard to treat metastatic breast cancer. Within this study cationic naproxen (NAP)-bearing polymeric nanoparticles (NPs) were obtained by self-assembly and they were coated with hyaluronic acid (HA) via electrostatic interaction. HA-coated and uncoated NAP-bearing NPs with different sizes were produced by changing the ionic strength of the aqueous preparation solutions (i.e. 300 and 350 nm or 100 and 130 nm in diameter, respectively). HA-NPs were fully characterized in terms of physicochemical parameters and biological response in cancer cells, macrophages and endothelial cells. Our results revealed that HA-coating of NPs provided a better control in NAP release and improved their hemocompatibility, while ensuring a strong CSC-targeting in MCF-7 breast cancer cells. Furthermore, the best polymeric NPs formulation significantly (p < 0.001) reduced MCF-7 cells viability when compared to free drug (i.e. 45 ± 6% for S-HA-NPs and 87 ± 10% for free NAP) by p53-dependent induction of apoptosis; and the migration of these cell line was also significantly (p < 0.01) reduced by the nano-formulated NAP (i.e. 76.4% of open wound for S-HA-NPs and 61.6% of open wound for NAP). This increased anti-cancer activity of HA-NAP-NPs might be related to the induction of apoptosis through alterations of the GSK-3β-related COX-independent pathway. Overall, these findings suggest that the HA-NAP-NPs have the potential to improve the treatment of advanced breast cancer by increasing the anti-proliferative effect of NAP within the CSC subpopulation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Stroke outcome data in Uganda is lacking. The objective of this study was to capture 30-day mortality outcomes in patients presenting with acute and subacute stroke to Mbarara Regional Referral Hospital (MRRH) in Uganda., Methods: A prospective study enrolling consecutive adults presenting to MRRH with abrupt onset of focal neurologic deficits suspicious for stroke, from August 2014 to March 2015. All patients had head computed tomography (CT) confirmation of ischemic or hemorrhagic stroke. Data was collected on mortality, morbidity, risk factors, and imaging characteristics., Results: Investigators screened 134 potential subjects and enrolled 108 patients. Sixty-two percent had ischemic and 38% hemorrhagic stroke. The mean age of all patients was 62.5 (SD 17.4), and 52% were female. More patients had hypertension in the hemorrhagic stroke group than in the ischemic stroke group (53% vs. 32%, p = 0.0376). Thirty-day mortality was 38.1% (p = 0.0472), and significant risk factors were National Institutes of Health Stroke Scale (NIHSS) score, female sex, anemia, and HIV infection. A one unit increase of the NIHSS on admission increased the risk of death at 30 days by 6%. Patients with hemorrhagic stroke had statistically higher NIHSS scores (p = 0.0408) on admission compared to patients with ischemic stroke, and also had statistically higher Modified Rankin Scale (mRS) scores at discharge (p = 0.0063), and mRS score change from baseline (p = 0.04)., Conclusions: Our study highlights an overall 30-day stroke mortality of 38.1% in southwestern Uganda, and identifies NIHSS at admission, female sex, anemia, and HIV infection as predictors of mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study examined the presence of neurodevelopmental regression and its effects on the clinical manifestations and the severity of autism spectrum disorder (ASD) in a group of children with autism compared with those without neurodevelopmental regression at the time of initial classification and subsequently. Methods and Subjects: ASD patients were classified into two subgroups, neurodevelopmental regressive (AMR) and non-regressive (ANMR), using a questionnaire based on the Autism Diagnostic Interview-Revised test. The severity of ASD and neurodevelopment were assessed with the Childhood Autism Rating Scale Test-2, Strengths and Difficulties Questionnaire , and Pervasive Developmental Disorders Behavior Inventory Parent Ratings (PDDBI) and with the Battelle Developmental Inventory tests at the beginning of the study and after 24 months of follow-up. Fifty-two patients aged 2-6 years with ASD were included. Nineteen were classified with AMR, and 33 were classified with ANMR. Results: The AMR subgroup presented greater severity of autistic symptoms and higher autism scores. Additionally, they showed lower overall neurodevelopment. The AMR subgroup at 24 months had poorer scores on the Battelle Developmental Inventory test in the following areas: Total personal/social ( p < 0.03), Total Motor ( p < 0.04), Expressive ( p < 0.01), and Battelle Total ( p < 0.04). On the PDDBI test, the AMR subgroup had scores indicating significantly more severe ASD symptoms in the variables: ritual score ( p < 0.038), social approach behaviors ( p < 0.048), expressive language ( p < 0.002), and autism score ( p < 0.003). Conclusions: ASD patients exhibited a set of different neurological phenotypes. The AMR and ANMR subgroups presented different clinical manifestations and prognoses in terms of the severity of autistic symptoms and neurodevelopment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martin-Borreguero, Gómez-Fernández, De La Torre-Aguilar, Gil-Campos, Flores-Rojas and Perez-Navero.)

Background: Maternity care practices such as skin-to-skin care, rooming-in, and direct breastfeeding are recommended, but it is unclear if these practices increase the risk of clinically significant COVID-19 in newborns, and if disruption of these practices adversely affects breastfeeding. Methods: We performed a retrospective cohort study of 357 mothers and their infants <12 months who had confirmed or suspected COVID-19. Subjects came from an anonymous worldwide online survey between May 4 and September 30, 2020, who were recruited through social media, support groups, and health care providers. Using multivariable logistic regression, Fisher's exact test, and summary statistics, we assessed the association of skin-to-skin care, feeding, and rooming-in with SARS-CoV-2 outcomes, breastfeeding outcomes, and maternal distress. Results: Responses came from 31 countries. Among SARS-CoV-2+ mothers whose infection was ≤3 days of birth, 7.4% of their infants tested positive. We found a nonsignificant decrease in risk of hospitalization among neonates who roomed-in, directly breastfed, or experienced uninterrupted skin-to-skin care ( p  > 0.2 for each). Infants who did not directly breastfeed, experience skin-to-skin care, or who did not room-in within arms' reach, were significantly less likely to be exclusively breastfed in the first 3 months, adjusting for maternal symptoms ( p  ≤ 0.02 for each). Nearly 60% of mothers who experienced separation reported feeling "very distressed," and 29% who tried to breastfeed were unable. Presence of maternal symptoms predicted infant transmission or symptoms (adjusted odds ratio = 4.50, 95% confidence interval = 1.52-13.26, p  = 0.006). Conclusion: Disruption of evidence-based quality standards of maternity care is associated with harm and may be unnecessary.

Public spaces could promote health equity by providing a place for people to engage in physical activity. Whereas most studies show a positive association between public spaces and physical activity, there are still mixed results, especially in low- and middle-income countries. The objectives of this mixed-methods study were: (i) to assess the quantitative association between access to public spaces and physical activity; (ii) to assess the modification of the association by public spaces quality, area-level walkability, and social stratifiers; (iii) to explain the quantitative results using qualitative data. Quantitative data were obtained with a household survey in two arid-climate Mexican cities in 2017-2018. physical activity was measured with the Global Physical Activity Questionnaire. Access to public spaces was measured in buffers centered on survey blocks, walkability with area-level indicators, and public spaces quality with the Physical Activity Resources Assessment. Qualitative data were obtained with semi-structured interviews and neighborhood observation. No quantitative association between access to public spaces and physical activity was found, as well as no interactions between access to public spaces and other variables. Walkability was positively associated with physical activity. Qualitative analysis showed that local public spaces were rarely used by adults because they were perceived as small, unequipped, unattractive, and unsafe. The results shed light on the relationship between public spaces and physical activity, highlighting the improvements in design and upkeep of public spaces that are necessary to achieve their potential health benefit.

Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR α ) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu 2+ /Zn 2+ and SOD Mn 2+ ), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Fabiola Cortes-Lopez et al.)

Interstitial cells of Cajal (ICCs) generate electrical slow waves, which are required for normal gastrointestinal motility. The mechanisms for generation of normal pacemaking are not fully understood. Normal gastrointestinal contractility - and electrical slow-wave activity depend on the presence of extracellular HCO 3 - . Previous transcriptional analysis identified enrichment of mRNA encoding the electrogenic Na + /HCO 3 - cotransporter (NBCe1) gene ( Slc4a4 ) in pacemaker myenteric ICCs in mouse small intestine. We aimed to determine the distribution of NBCe1 protein in ICCs of the mouse gastrointestinal tract and to identify the transcripts of the Slc4a4 gene in mouse and human small intestinal tunica muscularis. We determined the distribution of NBCe1 immunoreactivity (NBCe1-IR) by immunofluorescent labeling in mouse and human tissues. In mice, NBCe1-IR was restricted to Kit-positive myenteric ICCs of the stomach and small intestine and submuscular ICCs of the large intestine, that is, the slow wave generating subset of ICCs. Other subtypes of ICCs were NBCe1-negative. Quantitative real-time PCR identified >500-fold enrichment of Slc4a4-207 and Slc4a4-208 transcripts ["IP3-receptor-binding protein released by IP3" (IRBIT)-regulated isoforms] in Kit-expressing cells isolated from Kit creERT2/+ , Rpl22 tm1.1Psam/Sj mice and from single GFP-positive ICCs from Kit tm1Rosay mice. Human jejunal tunica muscularis ICCs were also NBCe1-positive, and SLC4A4-201 and SLC4A4-204 RNAs were >300-fold enriched relative to SLC4A4-202 . In summary, NBCe1 protein expressed in ICCs with electrical pacemaker function is encoded by Slc4a4 gene transcripts that generate IRBIT-regulated isoforms of NBCe1. In conclusion, Na + /HCO 3 - cotransport through NBCe1 contributes to the generation of pacemaker activity in subsets of ICCs. NEW & NOTEWORTHY In this study, we show that the electrogenic Na+/HCO 3 - cotransporter, NBCe1/Slc4a4, is expressed in subtypes of interstitial cells of Cajal (ICCs) responsible for electrical slow wave generation throughout the mouse gastrointestinal tract and is absent in other types of ICCs. The transcripts of Slc4a4 expressed in mouse ICCs and human gastrointestinal smooth muscle are the regulated isoforms. This indicates a key role for HCO 3 - transport in generation of gastrointestinal motility patterns.

An extensive database of sterols and triterpenoids isolated from Ganoderma mushrooms was evaluated by in silico structure-based virtual screening to determine their respective ligand affinities for the glucocorticoid or mineralocorticoid receptor (GCR or MNR). The main ligands for GCR in our database were ergosta-7,22-dien-3-one (compound 1) and ganodermaside B (compound 2), while the best ligands for MNR were 2β,3α,9α-trihydroxyergosta-7,22-diene (compound 8) and 5α-ergosta-7,22-dien-3β-ol (compound 3). The binding free energy (BFE) values calculated for such metabolites were similar to those of the natural ligands for each receptor (i.e., dexamethasone for GCR and aldosterone for MNR). Moreover, the differences between mean BFE values calculated for both receptors suggest that ergosta-7,22-dien-3-one (compound 1), ganodermaside B (compound 2), fungisterol (compound 5), ganoderic acid Ma (compound 9), and cerevisterol (compound 10) might be used as specific ligands for GCR, with a significantly lower affinity for MNR. Finally, it is worth noting that even though this work is exclusively theoretical, the reported bioactivities (either pro- or anti-inflammatory) for those metabolites that were previously studied are consistent with our findings, suggesting that the well-known immunomodulatory effect of Ganoderma triterpenoids and sterols might be attributed, at least partially, to their ability to act as specific GCR ligands.

Supplementary cementitious materials interact chemically and physically with cement, influencing the formation of hydrate compounds. Many authors have analyzed the filler and pozzolanic effect. However, few studies have explored the influence of these effects on hydration, properties in the fresh and hardened states, and durability parameters of cementitious composites separately. This study investigates the influence of the replacement of 20% of Portland cement for silica fume (SF) or a 20-µm medium diameter quartz powder (QP) on the properties of cementitious composites from the first hours of hydration to a few months of curing. The results indicate that SF is pozzolanic and that QP has no pozzolanic activity. The use of SF and QP reduces the released energy at early times to the control paste, indicating that these materials reduce the heat of hydration. The microstructure with fewer pores of SF compounds indicates that the pozzolanic reaction reduced pore size and binding capability, resulting in equivalent mechanical properties, reduced permeability and increased electrical resistance of the composites. SF and QP increase the carbonation depth of the composites. SF and QP composites are efficient in the inhibition of the alkali-aggregate reaction. The results indicate that, unlike the filler effect, the occurrence of pozzolanic reaction strongly influences electrical resistance, reducing the risk of corrosion of the reinforcement inserted in the concrete.

Sub-acute mastitis (SAM) is a prevalent disease among lactating women, being one of the main reasons for early weaning. Although the etiology and diagnosis of acute mastitis (AM) is well established, little is known about the underlying mechanisms causing SAM. We collected human milk samples from healthy and SAM-suffering mothers, during the course of mastitis and after symptoms disappeared. Total (DNA-based) and active (RNA-based) microbiota were analysed by 16S rRNA gene sequencing and qPCR. Furthermore, mammary epithelial cell lines were exposed to milk pellets, and levels of the pro-inflammatory interleukin IL8 were measured. Bacterial load was significantly higher in the mastitis samples and decreased after clinical symptoms disappeared. Bacterial diversity was lower in SAM milk samples, and differences in bacterial composition and activity were also found. Contrary to AM, the same bacterial species were found in samples from healthy and SAM mothers, although at different proportions, indicating a dysbiotic ecological shift. Finally, mammary epithelial cell exposure to SAM milk pellets showed an over-production of IL8. Our work therefore supports that SAM has a bacterial origin, with increased bacterial loads, reduced diversity and altered composition, which partly recovered after treatment, suggesting a polymicrobial and variable etiology.