Search

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.

Through two studies ( N  = 544 women), the role of types of relational problems (absence vs. presence of intimate partner violence [IPV]) in the use of conflict resolution strategies (exit and loyalty) was analyzed, considering the serial mediating effect of dependency and commitment and the moderating effect of benevolent sexism. The main results showed that higher scores in dependency and commitment predicted less use of exit strategies among women who reported IPV. No significant results were found regarding loyalty strategy and benevolent sexism. Ultimately, implications for women's perceived risk of future violence were discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The prevalence of diabetes has increased in last decades worldwide and is expected to continue to do so in the coming years, reaching alarming figures. Evidence have shown that patients with type 2 diabetes (T2D) have intestinal microbial dysbiosis. Moreover, several mechanisms link the microbiota with the appearance of insulin resistance and diabetes. Diet is a crucial factor related to changes in the composition, diversity, and activity of gut microbiota (GM). In this review, the current and future possibilities of nutrient-GM interactions as a strategy to alleviate T2D are discussed, as well as the mechanisms related to decreased low-grade inflammation and insulin resistance. A bibliographic search of clinical trials in Pubmed, Web of Science, and Scopus was carried out, using the terms "gut microbiota, diet and diabetes." The data analyzed in this review support the idea that dietary interventions targeting changes in the microbiota, including the use of prebiotics and probiotics, can improve glycemic parameters. However, these strategies should be individualized taking into account other internal and external factors. Advances in the understanding of the role of the microbiota in the development of metabolic diseases such as T2D, and its translation into a therapeutic approach for the management of diabetes, are necessary to allow a comprehensive approach.

Introduction: The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is important to individualize risk factors and develop predictive tools for their identification., Materials and Methods: This prospective observational study included 368 patients who were diagnosed with AD between 2016 and 2021 in a tertiary general university hospital during their first episode and who had a good response to antibiotic, percutaneous, or peritoneal lavage treatment. Univariate and multivariate Cox regression analyses of the variables associated with recurrence were performed. Subsequently, a predictive risk score was developed and validated through survival studies., Results: After a median follow-up of 50 months, there were 71 (19.3%) cases of recurrence out of a total of 368 patients. The mean time of recurrence was 15 months, and 73.3% of cases of recurrence occurred before 2 years of follow-up. Recurrence was independently associated with presentation with colonic perforation in the antimesenteric location (HR 3.67 95% CI [1.59-8.4]) and a CRP level greater than 100 mg/dl (HR 1.69 95% CI [1.04-2.77). A score with 5 variables was created that differentiated two risk groups: intermediate risk (0-3 points), with 19% recurrence and high risk (more than 3 points), with 42% recurrence., Conclusions: The risk of recurrence after the first episode of diverticulitis can be estimated using predictive scores. The detection of high-risk patients facilitates the individualization of follow-up and treatment., (© 2023 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Objective : The dystrophinopathies called Duchenne and Becker muscular dystrophies (DMD/BMD) are rare, progressive, incurable, and life-limiting paediatric-onset neuromuscular diseases. These diseases have long been associated with specific neuropsychological deficits. However, the performance of these patients in the social cognition domain has not been properly investigated. Thus, the main objective of this study was to compare the performance on social cognition between DMD/BMD patients and healthy age-matched boys. Method : This cross-sectional study included 20 DMD/BMD children and adolescents and 20 healthy controls. The protocol included the Social Perception Domain of the NEPSY-II, the Reading the Mind in the Eyes Test - Child and Happé's Strange Stories test. General intelligence was controlled to eliminate the possible influence of covariables. All the assessments were performed remotely. Results: Most social cognition tasks were worse in patients with DMD/BMD than in matched healthy controls. These differences remained even after controlling for the general intelligence variable, with the exception of Total Disgust Errors ( F  = 1.462, p = .234, η 2 p = .038) and Verbal task ( F  = 1.820, p = .185, η 2 p = .047) scores from the NEPSY-II. Conclusions : This is the first study to demonstrate that the neuropsychological domain of social cognition is impaired in DMD/BMD patients, independent of the level of general intelligence. Screening assessments in DMD/BMD patients should be promoted to allow social cognition difficulties to be detected at an early stage to enhance patients' quality of life and social development.

Although member checking is a well-established strategy for appraising credibility, there is a lack of research reporting procedures and outcomes when using this strategy. In recent years, scholars have implemented new member checking strategies along with several epistemological stances. In this work, researchers conducted member checking in three neighbourhoods with different socioeconomic status in Madrid, Spain. Attendance at member checking meetings was lower than expected. Member checking meetings were conducted in public halls within each neighbourhood and lasted approximately 2 hours. During the first hour, researchers introduced the aim of the meetings and shared summarized research findings with attendees using a slideshow. During the second hour, attendees had the opportunity to comment on any aspect of the research. Researchers used grounded theory coding strategies and a constructivist approach informed the analysis of the transcribed member checking meetings. One core category emerged, and it was named 'Co-constructing findings and side effects of the interaction between researchers and participants in member checking'. Member checking attendees contributed to co-constructing findings by means of underscore and disagreement. It is possible that these meetings might have caused side effects such as unintended comparisons between neighbourhoods and negative health-related behaviours. Attendees wondered how the findings could improve their neighbourhoods. The meetings allowed interaction between participants and researchers and resulted in appraising and co-constructing qualitative research findings. More research is needed to advance knowledge about member checking., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To translate, adapt and validate the psychometric properties of MoVac-flu scale in order to be used in Spanish., Method: The present research was an analytical observational study of cross-cultural adaptation and validation into Spanish of the MoVac-flu scale. It has been carried out between the months of March and July 2022. The sample size was 142 people who were obtained by consecutive sampling. The processes used for the adaptation have been translation, validation by a committee of experts, back-translation and pilot test. For validation, the psychometric properties of reliability, internal consistency, appearance validity, content validity, utility and ceiling-floor effect have been verified., Results: The internal consistency of the MoVac-flu scale in its version translated into Spanish was high, showing a McDonald's ω of 0.914., Conclusions: The MoVac-flu scale in Spanish allows to measure the degree of motivation towards vaccination against influenza in the adult population., (Copyright © 2023 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The aim of the study was to characterize the different ways in which, based on certain physical manifestations that an individual suddenly experiences, people judge the possibility that these manifestations indicate the onset of a heart attack., Methods: One hundred ninety-four French adults--plus six physicians--were presented with a set of realistic vignettes composed by orthogonally crossing the levels of four factors: the type of pain felt, and the presence or absence of nausea, excess sweating, and of difficulty breathing., Results: Four qualitatively different reactions were found among the lay people. The majority reaction (54%) was close to the physicians' reaction. It consisted of suspecting a heart attack as soon as intense pain occurs in the chest or back. The second reaction (25%) retained from the first one only the idea that a heart attack should be suspected if the pain is localized to the chest. The third reaction (14%) reflected some people's uncertainty in the face of disturbing manifestations that they find difficult to interpret. The fourth reaction (7%) was that no set of symptoms could mean, for them, the onset of a heart attack., Conclusion: Only about half of the participants appeared to be able to consider unpleasant physical manifestations as a whole and integrate that information into an overall warning judgment that can lead into prompt life-saving actions. We recommend that judgment training on warning symptoms and signs be performed, especially for high-risk patients, in the offices of primary care providers and specialists., Competing Interests: 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., (© 2023 The Author(s).)

Intimate partner violence against women (IPVAW) is a public health problem that affects women worldwide. Consequently, victims frequently go to healthcare centers, usually with a cover reason. To address this problem, national and autonomic protocols to respond to IPVAW in health systems have been developed in Spain. In this regard, the role of primary care physicians (PCPs) will be essential for addressing IPVAW, but they could encounter obstacles in doing so. The purpose of this study was to explore how IPVAW is addressed in healthcare centers in Spain. This study synthesized the information available in the protocols to address IPVAW among health care workers in Spain and analyzed it according to World Health Organization (WHO) guidelines. Additionally, PCPs' perspectives on these protocols and the nature of IPVAW attention from healthcare centers were explored through a focus group. The findings displayed that, although the protocols mostly conform to WHO guidelines, they are insufficient to address IPVAW. Generally, PCPs were unaware of the existence of the protocols and referred to the lack of training in IPVAW and protocol use as one of the main obstacles to intervening, along with a lack of time and feelings as well as cultural, educational, and political factors. The adoption of measures to ensure that PCPs apply these protocols correctly and to approach PCPs' obstacles for addressing IPVAW in consultations will be crucial for the care of victims.

We analysed the transmission of the human mpox virus in Spain by estimating the effective reproduction number of the disease from official surveillance data. Our computations show that this decreased steadily after an initial burst phase, dropping below 1 on July 12, and thus the outbreak was expected to reduce in the following weeks. Differences in trends were found across geographical regions of the country and across MSM and heterosexual populations.

Hearing loss is an important risk factor for the development of dementia, particularly Alzheimer's disease (AD). Mid-life hearing loss increases the risk of developing dementia by double any other single factor. However, given this strong connection between hearing loss and AD, the mechanisms responsible for this link are still unknown. Data from observational studies relating hearing loss and cognitive impairment, measured with standardized questionnaires, has shown a strong relationship between them. Similar findings have emerged from animal studies, showing that the induction of hearing loss via prolonged loud sound exposure or ear canal blocking, can impair cognitive abilities. Interestingly, patients with age-related hearing impairment exhibit increased phosphorylated tau in the cerebrospinal fluid, but no such relationship has been identified for amyloid-β. In addition, hearing loss predisposes to social isolation precipitating the development of dementia through a supposed reduction in cognitive load and processing requirements. Given this link between hearing loss and dementia, the question arises whether the restoration of hearing might mitigate against the onset or progress of AD. Indeed, there is a growing body of research that suggests that those who wear hearing aids for age-related hearing problems maintain better cognitive function over time than those who do not. These are compelling findings, as they suggest the use of hearing aids has the potential to be a cost-effective treatment for those with hearing loss both prior (for those at high risk for AD) and after the development of symptoms. This review aims to summarize the current theories that relate hearing loss and cognitive decline, present the key findings of animal studies, observational studies and summarize the gaps and limitations that need to be addressed in this topic. Through this, we suggest directions for future studies to tackle the lack of adequately randomized control trials in the field. This omission is responsible for the inability to provide a conclusive verdict on whether to use hearing interventions to target hearing-loss related cognitive decline., Competing Interests: MB-H and MS declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. 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 © 2023 Azeem, Julleekeea, Knight, Sohail, Bruyns-Haylett and Sastre.)

Background: The World Health Organization (WHO) developed an instrument to detect violence against women that has been widely used in several countries. Despite this instrument's importance in identifying intimate partner violence against women (IPVAW), it has not been adapted for the Spanish population. The aim of this study was to adapt and validate the WHO violence against women instrument in a sample in Spain, facilitating the detection of IPVAW in this context and comparisons between countries., Method: After the instrument was translated and adapted into Spanish, 532 women from the general population in Spain completed it. The initial instrument consisted of 28 items. We deleted three items due to low internal consistency, resulting in 25 items in the final version., Results: Suitable internal consistency was obtained through Confirmatory Factorial Analysis for physical (α = .92), psychological (α = .91), sexual (α = .86), and control behaviors subscales (α = .91) as well as for the total scale (α = .95). The instrument revealed highly prevalent IPVAW in our sample (79.7%)., Conclusions: The use of the Spanish version of the WHO violence against women instrument in Spain seems justified.

Ahead of Print article withdrawn by publisher. An 80-year-old woman presented necrotizing fasciitis on the right flank, requiring debridement. Tomography reported ascending colon neoplasm fistulized to the skin. Colonoscopy confirms adenocarcinoma. Intervention postponed due to rejection of surgery during the pandemic and SARS-COV-2 infection, producing progression with exteriorization of the neoplasm. A bloc laparotomic right hemicolectomy was performed (pT4bN0).

Background and Objective: The prevalence of hypersensitivity reactions to radiological contrast media (RCM) is increasing owing to the improved performance of diagnostic and therapeutic tests that require RCMs. Objective: We carried out a year-long real-life observational study to prospectively evaluate patients referred to the allergy department from primary care, the emergency department, and other specialties with suspected moderate-to-severe RCM hypersensitivity reactions., Methods: To study the costs of evaluating RCM hypersensitivity reactions, we systematically recorded direct and indirect costs., Results: Sixty-nine patients with previous reactions to RCM were evaluated in the allergy department from June 1, 2017, to May 31, 2018.Total direct health care costs were €10 715.84, with a mean (SD) cost per patient of €155.30 (77.08). Specifically, direct non-health care costs reached €1605.42 (mean, €23.27 [41.14]), and indirect costs were €6490.85 (mean, €94.07 [110.61]). In summary, the total cost was €18 812.11, that is, a mean cost of €272.64 (164.77)., Conclusion: Our study shows that the costs of an elective evaluation of hypersensitivity reactions to RCM are low, thus confirming that correct and safe management of affected patients are cost-effective. Therefore, our efforts should be directed toward ensuring the necessary logistics.

Background: Indocyanine green (ICG) near-infrared fluorescence cholangiography (NIRF-C) is widely used to visualize the biliary tract during laparoscopic cholecystectomy (LC). However, the ICG dose and its dosing time vary in the literature so there is not a standard ICG protocol. The objectives of this descriptive prospective study were to demonstrate that NIRF-C at a very low dose of ICG provides good visualization of the extrahepatic biliary tree while avoiding hepatic hyperluminescence and to assess the surgeon-perceived benefit. Furthermore, another additional aim was quantifying the amount of ICG dye in the liver tissue and biliary tract through a green colour intensity (GCI) analysis according to red green blue (RGB) color model and correlating it to surgeon-perceived benefit., Method: Forty-four patients were scheduled for LC. We recorded demographics, surgical indication, intraoperative details, adverse reactions to ICG, hepatic hyperluminescence, visualization of the cystic duct (CD), the common bile duct (CBD) and the cystic duct-bile duct junction (CDBDJ) before and after dissection of Calot's triangle, operation time, surgical complications and subjective surgeon data. For all procedures, a unique dose of 0.25 mg of ICG was administered intravenously during the anaesthetic induction. ICG NIRF-C was performed using the overlay mode of the VISERA ELITE II Surgical Endoscope in all surgeries. Video recordings of all 44 LC were reviewed. Using a color analysis software, the GCI of CBD versus adjacent liver tissue was calculated using RGB color model., Results: ICG NIRF-C was performed in all 44 cases. The mean operation time was 45 ± 15 min. There were no bile duct injuries (BDIs) or allergic reactions to ICG. The postoperative course was uneventful in all of cases. The mean postoperative hospital stay was 28 ± 4 h. ICG NIRF-C identified the CBD in 100% of the patients, the CD in 71% and the CDBDJ in 84%, with a surgeon satisfaction of 4/5 or 5/5 in almost 90% of surgeries based on a visual analogue scale (VAS). No statistically significant differences were found in the visualization of the biliary structures after the dissection of Calot's triangle in obese patients or with gallbladder inflammation. Furthermore, 25% of patients with a BMI ≥ 30, 27% of patients with a Nassar grade ≥ 3 and 21% of patients with gallbladder inflammation had a VAS score 5/5 compared to 6% of patients with a BMI < 30 (p = 0.215), 6% of patients with a Nassar grade < 3 (p = 0.083) and none of the patients without gallbladder inflammation (p = 0.037). Measured pixel GCI of CBD was higher than adjacent hepatic tissue for all cases regardless of the degree of gallbladder inflammation, the Nassar scale grades or the patient's BMI (p < 0.0001). In addition, a significant correlation was observed between surgeon-perceived benefit and the amount of ICG dye into the CBD according the RGB color model (p < 0.0001)., Conclusion: ICG NIRF-C at a very low dose of ICG (0.25 mg of ICG 20 min before surgery) enables the real-time identification of biliary ducts, thereby avoiding the hepatic hyperluminescence even in cases of obese patients or those with gallbladder inflammation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There is compelling evidence that head injury is a significant environmental risk factor for Alzheimer's disease (AD) and that a history of traumatic brain injury (TBI) accelerates the onset of AD. Amyloid-β plaques and tau aggregates have been observed in the post-mortem brains of TBI patients; however, the mechanisms leading to AD neuropathology in TBI are still unknown. In this study, we hypothesized that focal TBI induces changes in miRNA expression in and around affected areas, resulting in the altered expression of genes involved in neurodegeneration and AD pathology. For this purpose, we performed a miRNA array in extracts from rats subjected to experimental TBI, using the controlled cortical impact (CCI) model. In and around the contusion, we observed alterations of miRNAs associated with dementia/AD, compared to the contralateral side. Specifically, the expression of miR-9 was significantly upregulated, while miR-29b, miR-34a, miR-106b, miR-181a and miR-107 were downregulated. Via qPCR, we confirmed these results in an additional group of injured rats when compared to naïve animals. Interestingly, the changes in those miRNAs were concomitant with alterations in the gene expression of mRNAs involved in amyloid generation and tau pathology, such as β-APP cleaving enzyme (BACE1) and Glycogen synthase-3-β (GSK3β). In addition increased levels of neuroinflammatory markers (TNF-α), glial activation, neuronal loss, and tau phosphorylation were observed in pericontusional areas. Therefore, our results suggest that the secondary injury cascade in TBI affects miRNAs regulating the expression of genes involved in AD dementia.

Background: To study the effect of greater occipital nerve (GON) block on migraine-associated photophobia levels. Photophobia is one of the most bothersome symptoms reported by migraine patients. Studies investigating the impact of migraine treatment on this symptom are scarce., Methods: This is an observational prospective case-control study. Patients with migraine and photophobia attending a Headache Clinic were recruited. Cases were defined as patients in whom GON block was performed, following usual clinical practice guidelines. All patients were evaluated with the Hospital Anxiety and Depression Scale, the Migraine Specific Quality of Life Questionnaire, the Utah Photophobia Symptom Impact Scale (UPSIS-12), and the Korean Photophobia Questionnaire (KUMC-8); both in the first visit (V1) and one week after (V2)., Results: Forty-one patients were recruited, 28 (68.3%) cases and 13 (31.7%) controls. At V1, there were no significant differences in the median [p25-p75] score of UPSIS-12 in cases vs controls (32.0 [21.0-34.0] vs 30.5 [22.0-37.0], P = 0.497) or KUMC-8 (6.5 [5.5-7.0] vs 7.0 [6.0-8.0], P = 0.463). At V2, cases experimented a significant improvement in UPSIS-12 of -5.5 [-8.8 to -1.3] and in KUMC-8 of -0.5 [-2.0 to 0], whereas there were no significant changes in the control group. Migraine with aura patients presented higher UPSIS-12 score at V1 (33.5 [24.5-37.0] vs 26.0 [16.0-35.0]) and lesser improvement at V2 after GON block compared with migraine without aura patients (-4.0 [-6.0 to -1.0] vs -8.0 [-17.0 to -2.0]), although statistical significance was not achieved ( P = 0.643 and P = 0.122, respectively). There was no significant variation in the remaining scales., Conclusions: Greater occipital nerve block improves migraine-associated photophobia, measured with UPSIS-12 and KUMC-8. Patients without aura may exhibit a greater improvement. Physicians could consider GON block for management of photophobia in migraine patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer's disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6-month-old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition. Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD.

The new contexts of literary education allow for the creation of digital reading and writing practices related to what specialised literature calls digital literature. Among these practices and with an eminently theoretical content and with an example of this content, in this paper, we want to focus our gaze on cyberpoetry, conceived as an exercise in literary creativity that firstly involves use of technology and specific software for the digital creation of poetic texts and, last but not least, knowledge and mastery of poetic language and the literary conventions linked thereto. From this point of view, in initial teacher training, we work with future teachers to create cyberpoems with a dual purpose: on the one hand, to reflect on what literary reading in digital format entails and to rehearse reading mediation processes that can be carried out with this type of literature, and, on the other, to begin in the digital creation of cyberpoems that, later, may be presented and worked in a real context of the school classroom. In this paper, we present digital practices of literary reading that have been created by student teachers in initial training. The creation of these practices has been carried out with the Genially tool. For data collection, the URL of each creation is accessed in order to analyse them. The analysis of the data follows the parameters of the qualitative methodology, specifically based on three categories of analysis for each digital creation: multimodality, hypertextuality and the interaction of each digital reading proposal. The conclusions of all this allow us to affirm that the creation of cyberpoems is an exercise in literary creativity that has to take into account the digital dimension of the literary text and its reading comprehension in a multimodal environment. Thus, the teacher in initial training carries out a digital literary mediation exercise, of a creative type, which he will later carry out in his pedagogical practice., 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 Selfa Sastre and Falguera Garcia.)

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Introduction: We examined the scope of literature including non-parental caregiver involvement in child obesity prevention interventions., Methods: We conducted a scoping review following the Arksey and O'Malley framework, including only studies reporting the effect of an intervention on growth, weight, or early childhood obesity risk among children ages 0 to three years, published between 2000 and 2021. Interventions that did not include non-parental caregivers (adults regularly involved in childcare other than parents) were excluded., Results: Of the 14 studies that met the inclusion criteria, all were published between 2013 and 2020, and most interventions ( n = 9) were implemented in the United States. Eight of the 14 interventions purposefully included other non-parental caregivers: five included both parents and non-parental caregivers, and the remaining three included only non-parental caregivers. Most interventions ( n = 9) showed no significant impact on anthropometric outcomes. All interventions found improvements in at least one behavioral outcome (e.g., food groups intake ( n = 5), parental feeding practices ( n = 3), and screen time ( n = 2)). This review can inform future interventions that plan to involve non-parental caregivers, which may be beneficial in shaping early health behaviors and preventing obesity early in life.

The importance of cultivating creativity in language education has been widely acknowledged in the academic literature. In this respect, digital technologies can play a key role in achieving this endeavour. The socio-cultural conceptualization of creativity stresses the role of communication, collaboration and dialogical interaction of creative expression in language education. The objective of this paper is to study the literature focusing on cases of collaborative creativity and technology embedded in language education. To this end, we carry out a systematic revision of state-of-the-art literature consisting of 26 blind peer-reviewed empirical studies selected from several databases that address our main research question, namely, which specific roles and forms of digital technology can be identified in the existing literature that support collaborative creativity in language education. Results show that the features of digital technology unfold a range of learning opportunities in language education and can play three different roles in promoting collaborative creativity: (1) as a tutoring device that guides the implementation of key co-creation skills; (2) as a tool that enables and shapes the development of co-creative thinking skills; and (3) as a medium that creates rich and resourceful environments to stimulate the emergence of collective creative processes. The paper also reveals that these three roles can be performed using a wide range of interactive technologies that encourage students to participate in a rich, co-creative language learning experience and equip learners with key competences to approach complex problems in a globalised and hyper-connected world. Finally, this paper may contribute to developing future language technology-enhanced learning projects capable of promoting key collaborative and creative processes., 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 Selfa-Sastre, Pifarré, Cujba, Cutillas and Falguera.)

Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer's Disease (AD), with the prominent presence of reactive astrocytes surrounding amyloid-β plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demonstrated that astrocytes from AD brains are different from "normal" healthy astrocytes, showing dysregulations in areas such as neurotransmitter recycling, including glutamate and GABA, and impaired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology, worsening of the inflammatory profile, and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal models has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Copper is an essential trace element in living organisms with its levels and localisation being carefully managed by the cellular machinery. However, if misregulated, deficiency or excess of copper ions can lead to several diseases. Therefore, it is important to have reliable methods to detect, monitor and visualise this metal in cells. Herein we report a new optical probe based on BODIPY, which shows a switch-on in its fluorescence intensity upon binding to copper(I), but not in the presence of high concentration of other physiologically relevant metal ions. More interestingly, binding to copper(I) leads to significant changes in the fluorescence lifetime of the new probe, which can be used to visualize copper(I) pools in lysosomes of live cells via fluorescence lifetime imaging microscopy (FLIM)., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

11 C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18 F-florbetaben and 11 C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher 11 C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11 C-BU99008 and 18 F-florbetaben. Autoradiography using 3 H-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased 3 H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11 C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity., (© 2021. The Author(s).)

Alzheimer's disease, characterized by brain deposits of amyloid-β plaques and neurofibrillary tangles, is also linked to neurovascular dysfunction and blood-brain barrier breakdown, affecting the passage of substances into and out of the brain. We hypothesized that treatment of neurovascular alterations could be beneficial in Alzheimer's disease. Annexin A1 (ANXA1) is a mediator of glucocorticoid anti-inflammatory action that can suppress microglial activation and reduce blood-brain barrier leakage. We have reported recently that treatment with recombinant human ANXA1 (hrANXA1) reduced amyloid-β levels by increased degradation in neuroblastoma cells and phagocytosis by microglia. Here, we show the beneficial effects of hrANXA1 in vivo by restoring efficient blood-brain barrier function and decreasing amyloid-β and tau pathology in 5xFAD mice and Tau-P301L mice. We demonstrate that young 5xFAD mice already suffer cerebrovascular damage, while acute pre-administration of hrANXA1 rescued the vascular defects. Interestingly, the ameliorated blood-brain barrier permeability in young 5xFAD mice by hrANXA1 correlated with reduced brain amyloid-β load, due to increased clearance and degradation of amyloid-β by insulin degrading enzyme (IDE). The systemic anti-inflammatory properties of hrANXA1 were also observed in 5xFAD mice, increasing IL-10 and reducing TNF-α expression. Additionally, the prolonged treatment with hrANXA1 reduced the memory deficits and increased synaptic density in young 5xFAD mice. Similarly, in Tau-P301L mice, acute hrANXA1 administration restored vascular architecture integrity, affecting the distribution of tight junctions, and reduced tau phosphorylation. The combined data support the hypothesis that blood-brain barrier breakdown early in Alzheimer's disease can be restored by hrANXA1 as a potential therapeutic approach., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Neurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage. We developed a high-fidelity multiscale finite element model of the rat brain featuring a detailed definition of the angioarchitecture. Controlled cortical impacts were performed experimentally and in-silico. The model was able to predict the pattern of blood-brain barrier damage. We found strong correlation between the area of fibrinogen extravasation and the brain area where axial strain in vessels exceeds 0.14. Our results showed that adjacent vessels can sustain profoundly different axial stresses depending on their alignment with the principal direction of stress in parenchyma, with a better alignment leading to larger stresses in vessels. We also found a strong correlation between axial stress in vessels and the shearing component of the stress wave in parenchyma. Our multiscale computational approach explains the unrecognised role of the vascular anatomy and shear stresses in producing distinct distribution of large forces in vasculature. This new understanding can contribute to improving TBI diagnosis and prevention.

The peroxisome proliferator-activated receptor co-activator-1α (PGC1α) belongs to a family of transcriptional regulators, which act as co-activators for a number of transcription factors, including PPARs, NRFs, oestrogen receptors, etc. PGC1α has been implicated in the control of mitochondrial biogenesis, the regulation of the synthesis of ROS and inflammatory cytokines, as well as genes controlling metabolic processes. The levels of PGC1α have been shown to be altered in neurodegenerative disorders. In the brains of Alzheimer's disease (AD) patients and animal models of amyloidosis, PGC1α expression was reduced compared with healthy individuals. Recently, it was shown that overexpression of PGC1α resulted in reduced amyloid-β (Aβ) generation, particularly by regulating the expression of BACE1, the rate-limiting enzyme involved in the production of Aβ. These results provide evidence pointing toward PGC1α activation as a new therapeutic avenue for AD, which has been supported by the promising observations of treatments with drugs that enhance the expression of PGC1α and gene therapy studies in animal models of AD. This review summarizes the different ways and mechanisms whereby PGC1α can be neuroprotective in AD and the pre-clinical treatments that have been explored so far.

Purpose: The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abundance. Here, we report 11 C-labeling, in vivo stability, biodistribution, and longitudinal study on BChE abundance in the brains of control and 5xFAD (AD model) animals, using a potent BChE selective inhibitor, [ 11 C] 4 , and positron emission tomography (PET) in combination with computerised tomography (CT). We correlate the results with in vivo amyloid beta (Aβ) deposition, longitudinally assessed by [ 18 F]florbetaben-PET imaging. Methods : [ 11 C] 4 was radiolabelled through 11 C-methylation. Metabolism studies were performed on blood and brain samples of female wild type (WT) mice. Biodistribution studies were performed in female WT mice using dynamic PET-CT imaging. Specific binding was demonstrated by ex vivo and in vivo PET imaging blocking studies in female WT and 5xFAD mice at the age of 7 months. Longitudinal PET imaging of BChE was conducted in female 5xFAD mice at 4, 6, 8, 10 and 12 months of age and compared to age-matched control animals. Additionally, Aβ plaque distribution was assessed in the same mice using [ 18 F]florbetaben at the ages of 2, 5, 7 and 11 months. The results were validated by ex vivo staining of BChE at 4, 8, and 12 months and Aβ at 12 months on brain samples. Results : [ 11 C] 4 was produced in sufficient radiochemical yield and molar activity for the use in PET imaging. Metabolism and biodistribution studies confirmed sufficient stability in vivo , the ability of [ 11 C] 4 to cross the blood brain barrier (BBB) and rapid washout from the brain. Blocking studies confirmed specificity of the binding. Longitudinal PET studies showed increased levels of BChE in the cerebral cortex, hippocampus, striatum, thalamus, cerebellum and brain stem in aged AD mice compared to WT littermates. [ 18 F]Florbetaben-PET imaging showed similar trend of Aβ plaques accumulation in the cerebral cortex and the hippocampus of AD animals as the one observed for BChE at ages 4 to 8 months. Contrarily to the results obtained by ex vivo staining, lower abundance of BChE was observed in vivo at 10 and 12 months than at 8 months of age. Conclusions: The BChE inhibitor [ 11 C] 4 crosses the BBB and is quickly washed out of the brain of WT mice. Comparison between AD and WT mice shows accumulation of the radiotracer in the AD-affected areas of the brain over time during the early disease progression. The results correspond well with Aβ accumulation, suggesting that BChE is a promising early biomarker for incipient AD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Astrocytes provide a vital support to neurons in normal and pathological conditions. In Alzheimer's disease (AD) brains, reactive astrocytes have been found surrounding amyloid plaques, forming an astrocytic scar. However, their role and potential mechanisms whereby they affect neuroinflammation, amyloid pathology, and synaptic density in AD remain unclear., Methods: To explore the role of astrocytes on Aβ pathology and neuroinflammatory markers, we pharmacologically ablated them in organotypic brain culture slices (OBCSs) from 5XFAD mouse model of AD and wild-type (WT) littermates with the selective astrocytic toxin L-alpha-aminoadipate (L-AAA). To examine the effects on synaptic circuitry, we measured dendritic spine number and size in OBCSs from Thy-1-GFP transgenic mice incubated with synthetic Aβ42 or double transgenics Thy-1-GFP/5XFAD mice treated with LAAA or vehicle for 24 h., Results: Treatment of OBCSs with L-AAA resulted in an increased expression of pro-inflammatory cytokine IL-6 in conditioned media of WTs and 5XFAD slices, associated with changes in microglia morphology but not in density. The profile of inflammatory markers following astrocytic loss was different in WT and transgenic cultures, showing reductions in inflammatory mediators produced in astrocytes only in WT sections. In addition, pharmacological ablation of astrocytes led to an increase in Aβ levels in homogenates of OBCS from 5XFAD mice compared with vehicle controls, with reduced enzymatic degradation of Aβ due to lower neprilysin and insulin-degrading enzyme (IDE) expression. Furthermore, OBSCs from wild-type mice treated with L-AAA and synthetic amyloid presented 56% higher levels of Aβ in culture media compared to sections treated with Aβ alone, concomitant with reduced expression of IDE in culture medium, suggesting that astrocytes contribute to Aβ clearance and degradation. Quantification of hippocampal dendritic spines revealed a reduction in their density following L-AAA treatment in all groups analyzed. In addition, pharmacological ablation of astrocytes resulted in a decrease in spine size in 5XFAD OBCSs but not in OBCSs from WT treated with synthetic Aβ compared to vehicle control., Conclusions: Astrocytes play a protective role in AD by aiding Aβ clearance and supporting synaptic plasticity.

Background and Objective: Being labeled as allergic to penicillin (unverified ß-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. Objective: We aimed to evaluate the real costs of evaluating ß-lactam allergy., Methods: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected ß-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism., Results: A total of 296 patients with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were €28 176.70, with a mean (SD) cost of €95.19 (37.20). Direct nonhealth costs reached €6551.73, that is, €22.13 (40.44) per patient. Indirect health costs reached €20 769.20, with a mean of €70.17 (127.40). In summary, the total cost was €55 497.63, that is, a cost per patient of €187.49 (148.14)., Conclusions: When all possible costs are taken into account, the evaluation of ß-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics.

The relationship between biomechanical forces and neuropathology is key to understanding traumatic brain injury. White matter tracts are damaged by high shear forces during impact, resulting in axonal injury, a key determinant of long-term clinical outcomes. However, the relationship between biomechanical forces and patterns of white matter injuries, associated with persistent diffusion MRI abnormalities, is poorly understood. This limits the ability to predict the severity of head injuries and the design of appropriate protection. Our previously developed human finite element model of head injury predicted the location of post-traumatic neurodegeneration. A similar rat model now allows us to experimentally test whether strain patterns calculated by the model predicts in vivo MRI and histology changes. Using a controlled cortical impact, mild and moderate injuries (1 and 2 mm) were performed. Focal and axonal injuries were quantified with volumetric and diffusion 9.4 T MRI at 2 weeks post injury. Detailed analysis of the corpus callosum was conducted using multi-shell diffusion MRI and histopathology. Microglia and astrocyte density, including process parameters, along with white matter structural integrity and neurofilament expression were determined by quantitative immunohistochemistry. Linear mixed effects regression analyses for strain and strain rate with the employed outcome measures were used to ascertain how well immediate biomechanics could explain MRI and histology changes. The spatial pattern of mechanical strain and strain rate in the injured cortex shows good agreement with the probability maps of focal lesions derived from volumetric MRI. Diffusion metrics showed abnormalities in the corpus callosum, indicating white matter changes in the segments subjected to high strain, as predicted by the model. The same segments also exhibited a severity-dependent increase in glia cell density, white matter thinning and reduced neurofilament expression. Linear mixed effects regression analyses showed that mechanical strain and strain rate were significant predictors of in vivo MRI and histology changes. Specifically, strain and strain rate respectively explained 33% and 28% of the reduction in fractional anisotropy, 51% and 29% of the change in neurofilament expression and 51% and 30% of microglia density changes. The work provides evidence that strain and strain rate in the first milliseconds after injury are important factors in determining patterns of glial and axonal injury and serve as experimental validators of our computational model of traumatic brain injury. Our results provide support for the use of this model in understanding the relationship of biomechanics and neuropathology and can guide the development of head protection systems, such as airbags and helmets., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Activation of type 2 imidazoline receptors has been shown to exhibit neuroprotective properties including anti-apoptotic and anti-inflammatory effects, suggesting a potential therapeutic value in Alzheimer's disease (AD). Here, we explored the effects of the imidazoline-2 ligand BU224 in a model of amyloidosis., Experimental Approach: Six-month-old female transgenic 5XFAD and wild-type (WT) mice were treated intraperitoneally with 5-mg·kg -1 BU224 or vehicle twice a day for 10 days. Behavioural tests were performed for cognitive functions and neuropathological changes were investigated by immunohistochemistry, Western blot, elisa and qPCR. Effects of BU224 on amyloid precursor protein (APP) processing, spine density and calcium imaging were analysed in brain organotypic cultures and N2a cells., Key Results: BU224 treatment attenuated spatial and perirhinal cortex-dependent recognition memory deficits in 5XFAD mice. Fear-conditioning testing revealed that BU224 also improved both associative learning and hippocampal- and amygdala-dependent memory in transgenic but not in WT mice. In the brain, BU224 reduced levels of the microglial marker Iba1 and pro-inflammatory cytokines IL-1β and TNF-α and increased the expression of astrocytic marker GFAP in 5XFAD mice. These beneficial effects were not associated with changes in amyloid pathology, neuronal apoptosis, mitochondrial density, oxidative stress or autophagy markers. Interestingly, ex vivo and in vitro studies suggested that BU224 treatment increased the size of dendritic spines and induced a threefold reduction in amyloid-β (Aβ)-induced functional changes in NMDA receptors., Conclusion and Implications: Sub-chronic treatment with BU224 restores memory and reduces inflammation in transgenic AD mice, at stages when animals display severe pathology., (© 2020 The British Pharmacological Society.)

Scholars have determined that low socioeconomic status (SES) is associated with unhealthy dietary behaviours and that local food environments shape food inequality. Less is known about how residents' perceptions of their food environment affect their dietary behaviours. We conducted 37 semistructured interviews and 29 focus groups in three socioeconomically distinct neighbourhoods in Madrid. We identified the following main categories related to social and physical food environments: (a) perceptions of healthy and unhealthy dietary behaviours, (b) children's relationships with food, (c) precariousness and (d) residential food retailer types. Older adults were perceived as healthier consumers, whereas younger people were identified as fast-food consumers. In the low- and middle-SES neighbourhoods, residents saw home-cooked legume-based stews as healthy food. In the high-SES neighbourhood, television cooking programs were highlighted as a positive influence. In the low- and middle-SES neighbourhoods, grandparents played an essential role in the transmission of healthy eating habits to their grandchildren. In the high-SES neighbourhood, children's diets at home were determined by school menus. In the low- and middle-SES neighbourhoods, participants talked about a black market where food could be purchased. Food retailers with low-quality foods were also highlighted. In all neighbourhoods, residents missed traditional food stores, and in the low- and middle-SES neighbourhoods, immigrant-run food stores were not well accepted. Our study presents the concepts shaping how neighbourhood SES differences affect dietary behaviours according to residents of a large Mediterranean city., Competing Interests: Declaration of competing interest The authors of this article do not report any conflicts of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Multimerization is a key process in prion-like disorders such as Alzheimer's disease (AD), since it is a requirement for self-templating tau and beta-amyloid amyloidogenesis. AT8-immunohistochemistry for hyperphosphorylated tau is currently used for the diagnosis and staging of tau pathology. Given that tau-tau interactions can occur in the absence of hyperphosphorylation or other post-translational modifications (PTMs), the direct visualization of tau multimerization could uncover early pathological tau multimers., Methods: Here, we used bimolecular fluorescent complementation, rapamycin-dependent FKBP/FRB-tau interaction and transmission electron microscopy to prove the in vitro specificity of tau-proximity ligation assay (tau-PLA). We then analyzed MAPT KO and P301S transgenic mice, and human hippocampus and temporal isocortex of all Braak stages with tau-PLA and compared it with immunohistochemistry for the diagnostic antibody AT8, the early phosphorylation-dependent AT180, and the conformational-dependent antibody MC1. Finally, we performed proteinase-K treatment to infer the content of amyloidogenic beta-sheet fold., Results: Our novel tau-proximity ligation assay (tau-PLA) directly visualized tau-tau interactions in situ, and exclusively recognized tau multimers but not monomers. It elicited no signal in MAPT KO mouse brains, but extensively labelled P301S transgenic mice and AD brain. Two groups of structures were detected, a previously unreported widespread small-sized diffuse pathology and large, neurofibrillary-like lesions. Tau-PLA-labelled diffuse pathology appeared from the earliest Braak stages, mostly unaccompanied by tangle-like tau-immunohistochemistry, being significantly more sensitive than any small-sized dot-/thread-like pathology labelled by AT180-, AT8- and MC1-immunohistochemistry in most regions quantified at stages 0-II. Tau-PLA-labelled diffuse pathology was extremely sensitive to Proteinase-K, in contrast to large lesions., Conclusions: Tau-PLA is the first method to directly visualize tau multimers both in vitro and in situ with high specificity. We find that tau multimerization appears extensively from the earliest presymptomatic Braak stages as a previously unreported type of diffuse pathology. Importantly, in our study multimerization is the earliest detectable molecular event of AD tau pathology. Our findings open a new window to the study of early tau pathology, with potential implications in early diagnosis and the design of therapeutic strategies.

Purpose: To determinate the variation in thickness of the individual choroidal layers in patients with central serous chorioretinopathy treated with half-fluence photodynamic therapy., Methods: Twenty-two eyes were evaluated with spectral-domain optical coherence tomography. The images were taken before photodynamic therapy, 3 months, and 6 months after the treatment. Two investigators performed these measurements: 1) choroidal thickness (CT), 2) Haller layer thickness, defined as the most external layer containing a 100-μm vessel, and 3) choriocapillaris + Sattler layer (C&S). Nine measurements were taken in the macular region., Results: Choroidal thickness before photodynamic therapy was 471.8 µm ± 145.8. The Haller layer was 358.4 µm ± 122.6, and C&S was 114.3 µm ± 27.8. At 3-month follow-up, CT was 441.1 µm ± 150.7, Haller layer 348.8 µm ± 127.6, and C&S 92.4 µm ± 27.9. At 6-month follow-up, CT was 420.4 µm ± 118.4, Haller layer 331.8 µm ± 97.2, and C&S 89.5 µm ± 28.0. Using a multilevel mixed-effects linear regression, CT was found to be reduced at both 3 months (P < 0.03) and at 6 months (P < 0.001), Haller layer showed no significant reduction at 3 months (P = 0.483) or at 6 months (P = 0.055), and C&S showed reduction at 3 months (P < 0.001) and at 6 months (P < 0.001). Fellow nonaffected eyes showed no statistical variation at 3-month and 6-month follow-up., Conclusion: Reduction in CT in patients affected by central serous chorioretinopathy after half-fluence photodynamic therapy occurs primarily in the choriocapillaris and medium diameter vessel layers of the choroid in a short- and medium-term follow-up.

Objective: To describe the semiology of pain and its associated features in patients with coronavirus disease 2019 (COVID-19) and headache presenting to the emergency department who do not require urgent services., Background: Headache is one of the most frequent neurological symptoms reported in case series, epidemiological studies, and meta-analyses of COVID-19, with a prevalence ranging from 8 to 71.1%. Studies addressing the semiology of these headaches are lacking., Methods: We conducted a cross-sectional study in the emergency department of a tertiary hospital. Patients classified according to the Manchester Triage System as standard and non-urgent and those fulfilling the criteria for probable or confirmed COVID-19 according to World Health Organization guidelines who presented with headache were included. A standardized questionnaire was used for data collection., Results: Of the 145 confirmed and probable COVID-19 patients, 99 (68.3%) reported headache. A total of 54/99 (54.5%) were classified with probable COVID-19 and 45/99 (45.5%) with confirmed COVID-19. The mean age (44.7 ± 11.8 vs 40.4 ± 10.7, P = .061), sex distribution (35/54 [64.8%] vs 28/45 [62.2%] female, P = .768), and headache comorbidity (19/54 [35.2%] vs 17/45 [37.8%], P = .789) were similar between the probable and confirmed COVID-19 groups, along with other medical comorbidities and laboratory data. Patients with confirmed COVID-19 showed a higher incidence of anosmia (21/54 [38.9%] vs 28/45 [62.2%], P = .021) and pneumonia (10/54 [18.5%] vs 18/45 [40%], P = .018), headache at onset (32/54 [59.3%] vs 39/45 [86.7%], P = .002), and hospital admission (0/54 [0%] vs 2/45 [11.1%], P = .017). In most cases, the headache appeared simultaneously with other COVID-19 symptoms (57/99, 57.6%). It was bilateral (86/99, 86.9%), frontal or holocranial (34/99, 34.3% each) in location and intense (60/99, 60.6%, reported a visual analog scale [VAS] score ≥7). A total of 39/99 (39.4%) identified triggers, most commonly fever. The most frequent aggravating factors were physical activity (45/99, 45.5%) and coughing (43/99, 43.4%). Patients showed a propensity toward prostration (41/99, 41.4%), photophobia (29/99, 29.3%), and phonophobia (27/99, 27.3%). Partial (53/99, 53.5%) or total (26/99, 26.3%) responses to first-step analgesics were reported. A total of 25/99 (25.3%) patients had a prior history of migraine, presenting with headache different from the usual in 23/25 (92.0%) patients. Individuals with migraine were more likely to have earlier (headache at onset of the respiratory symptoms in 24/25 [96.0%] vs 57/74 [77.0%], P = .023 [95% CI: 0.067, 0.313]), longer (>24 hours of pain in 20/25 [80%] vs 25/74 [33.8%], P < .001 [95% CI: 0.272, 0.652]), and more intense (VAS score ≥5 in 25/25 [100%] vs 63/74 [85.1%], P = .043 [95% CI: 0.057, 0.213]) headaches than patients without migraine., Conclusions: Headache is a very prevalent COVID-19 symptom among patients presenting to the emergency room, most frequently presenting as holocranial or bifrontal moderate to severe, and pressing quality headache. Individuals with migraine tend to present with earlier, longer, and more intense headaches., (© 2020 American Headache Society.)

Objective: To evaluate the costs associated with evaluation of β-lactam allergy in children labeled as allergic., Study Design: We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected β-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic., Results: A total of 40 children with suspected allergy to β-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient., Conclusions: Elective evaluation of β-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Spanish population presents higher levels of loneliness than citizens of countries in Northern Europe. Numerous studies have linked loneliness to increased morbidity and mortality, but very few studies have associated loneliness with healthy lifestyles. The objectives of this research are to identify the feeling of unwanted loneliness in various age and gender groups in the city of Alcalá de Henares (Madrid, Spain), to determine lifestyle habits in the areas of diet and physical exercise, and to examine the association between lifestyle habits and perceived loneliness., Methods: A cross-sectional, observational and analytical study on the perception of loneliness among men (59.06%) and women (60.06%) in a sample ( n = 611) of the general population (N = 198,945), by means of random assignment of a health survey, was conducted. The data were collected using an ad hoc questionnaire. The data were stratified and analyzed with the IBM SSPS ® v.25 software package., Results: The frequency of loneliness is stratified by sex and age, and healthy lifestyle habits in terms of diet and physical exercise are analyzed., Conclusions: People with perceived loneliness do not have worse lifestyle habits. However, women living with other people have a higher perception of loneliness than those living alone. Specifically, the perception of loneliness in young adult women could suggest a low level of moderate physical exercise.

Background: We sought to assess the potential of insulin resistance (IR) for estimating cardiovascular disease (CVD) risk in adults with type 1 diabetes (T1DM) according to the scores of the Steno Type 1 Risk Engine (ST1RE)., Methods: A total of 179 adults with T1DM (50.8% men, age 41.2 ± 13.1 years, duration of T1DM 16 (12-23) years) without established CVD were evaluated. IR was assessed by the estimation of insulin sensitivity (eIS) using two validated prediction equations: the estimated insulin sensitivity developed from the Pittsburgh Epidemiology of Diabetes Complications Study (eIS-EDC) and the estimated insulin sensitivity developed from Coronary Artery Calcification in T1DM Study (eIS-CACTI) ST1RE was used to estimate 10-year CVD risk and to classify subjects into three groups according to their risk: low (<10%; n = 105), moderate (10-20%; n = 53), and high (≥20%; n = 21)., Results: Both eIS-EDC and eIS-CACTI correlated negatively with ST1RE scores (eIS-EDC: r = -0.636, p < 0.001; eIS-CACTI: r = -0.291, p < 0.001). The C-statistic for predicting moderate/high risk and high risk was 0.816 (95% confidence interval (CI): 0.754-0.878) and 0.843 (95% CI: 0.772-0.913), respectively, for the eIS-EDC equation, and was 0.686 (95% CI: 0.609-0.763) and 0.646 (95% CI: 0.513-0.778), respectively, for the eIS-CACTI equation. The eIS-EDC equation had a significantly higher C-statistic both for moderate-/high-risk ( p = 0.001) and high-risk ( p = 0.007) subjects. Two cut-off points of eIS-EDC were identified for detecting moderate/high risk (8.52 mg·kg -1 ·min -1 ; sensitivity 74% and specificity 76%) and high risk (8.08 mg·kg -1 ·min -1 ; sensitivity 65% and specificity 95%) with potential applicability in clinical practice., Conclusions: eIS negatively correlates with the score of CVD risk in the ST1RE. Two cut-off points of eIS are reported with potential utility in clinical practice for detecting adults with T1DM with the highest CVD risk.

Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves ( Olea europaea L. ), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured lipid carriers (NLCs) were proposed for OLE encapsulation to protect and improve its antioxidant efficacy. The lipid matrix, composed of olive oil and Precirol, was optimized prior to OLE encapsulation. The characterization of the optimized oleuropein-loaded NLCs (NLC-OLE) showed a mean size of 150 nm, a zeta potential of -21 mV, an encapsulation efficiency of 99.12%, sustained release profile, and improved radical scavenging activity. The cellular in vitro assays demonstrated the biocompatibility of the NLCs, which were found to improve and maintain OLE antioxidant efficacy in the A549 and CuFi-1 lung epithelial cell lines, respectively. Overall, these findings suggest a promising potential of NLC-OLE to further design a pulmonary formulation for OLE delivery in lung epithelia., Competing Interests: The authors declare no conflicts of interest.

The role of astrocytes in the progression of Alzheimer's disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP-TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased levels of monomeric amyloid-β (Aβ) in brain homogenates, associated with reduced enzymatic degradation and clearance mechanisms. In addition, our data revealed exacerbated memory deficits in mice lacking proliferating astrocytes concomitant with decreased levels of synaptic markers and higher expression of pro-inflammatory cytokines. Our data suggest that loss of reactive astrocytes in AD aggravates amyloid pathology and memory loss, possibly via disruption of amyloid clearance and enhanced neuroinflammation., (© 2019 The Authors. Glia published by Wiley Periodicals, Inc.)

Objective: Qualitative methods may help to understand features related to health urban inequalities as a way to include citizens' perceptions of their neighbourhoods in relation to their health-related behaviours. The aim of this article is to describe the methods and design of a qualitative urban health study., Methods: The Heart Healthy Hoods (HHH) analyses cardiovascular health in an urban environment using mixed methods: electronic health records, quantitative individual questionnaires, physical examination, semi-structured Interviews (SSIs), focus groups (FGs) and participatory technics such as photovoice. This article focuses on the HHH qualitative methods and design. A case study was used to select three neighbourhoods in Madrid with different socioeconomic levels: low, medium, and high. The selection process for these three neighbourhoods was as follows: classification of all Madrid's neighbourhoods (128) according to their socioeconomic level; after ranking this classification, nine neighbourhoods, three by socioeconomic level, were short-listed; different urban sociology criteria and non-participant observation were used for the final selection of three neighbourhoods. After selecting the three neighbourhoods, thirty SSIs were held with residents and six SSIs were held with key informants. Finally, twenty-nine FGs will be conducted over the course of 8 months, between May and December of 2018., Conclusions: Systematization in the selection of neighbourhoods and the use of adequate techniques are essential for the qualitative study of urban health inequalities., (Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Currently used risk scores for type 2 diabetes mellitus (T2DM) clearly underestimate cardiovascular risk in type 1 diabetes (T1DM). Hence, there is a need to develop novel and specific risk-estimation tools for this population. We aimed to assess the relationship between the Steno Type 1 Risk Engine (ST1RE) and arterial stiffness (AS), and to identify potential cut-off points of interest in clinical practice., Design and Methods: A total of 179 patients with T1DM (50.8% men, mean age 41.2±13.1 years), without established cardiovascular disease, were evaluated for clinical and anthropometric data (including classical cardiovascular risk factors), and AS measured by aortic pulse-wave velocity (aPWV). The ST1RE was used to estimate 10-year cardiovascular risk and patients were classified into 3 groups: low- (<10%; n = 105), moderate- (10-20%; n = 53) and high-risk (≥20%; n = 21)., Results: When compared with the low- and moderate-risk groups, patients in the high-risk group were older, had higher prevalence of hypertension, dyslipidemia and insulin-resistance, and had higher body-mass index and HbA1c. aPWV increased in parallel with estimated cardiovascular risk (6.4±1.0, 8.4±1.3 and 10.3±2.6m/s; p<0.001). As an evaluation of model performance, the C-statistic of aPWV was 0.914 (95% confidence interval [CI]:0.873-0.950) for predicting moderate/high-risk and 0.879 (95%CI:0.809-0.948) for high-risk, according to the ST1RE. The best cut-off points of aPWV were 7.3m/s (sensitivity:86%, specificity:83%) and 8.7m/s (sensitivity:76%, specificity:86%) for moderate/high- and high-risk, respectively., Conclusions: AS is highly correlated with the scores obtained from the ST1RE. We have identified two cut-off points of AS that can clearly discriminate moderate/high- and high-risk T1DM patients, which could be of great value in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

The usefulness of nanotechnology to increase the bioavailability of drugs and decrease their toxicity may be a tool to deal with multiresistant P. aeruginosa (Mr-Pa) respiratory infections. We describe the preparation and the in vivo efficacy and safety of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) by the pulmonary and intramuscular routes. Nanoparticles showed 1-2 mg/L minimum inhibitory concentration against eight extensively drug-resistant P. aeruginosa strains. In vivo, SCM-NLC displayed significantly lower CFU/g lung than the saline and similar to that of the free SCM, even the dose in SCM-NLC group was lower than free SCM. There was no tissue damage related to the treatments. Biodistribution assessments showed a mild systemic absorption after nebulization and a notorious absorption after IM route. Altogether, it could be concluded that SCM-NLC were effective against P. aeruginosa in vivo, not toxic and distribute efficiently to the lung and liver after pulmonary or intramuscular administrations., (Copyright © 2019 Elsevier Inc. All rights reserved.)