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Abstract Background The coronavirus disease 2019 (COVID-19) pandemic caused significant global disruptions to the healthcare system, which was forced to make rapid changes in healthcare delivery. The pandemic necessitated closer collaboration between the US civilian healthcare sector and the military health system (MHS), resulting in new and strengthened partnerships that can ultimately benefit public health and healthcare for the nation. In this study, we sought to understand the full range of partnerships in which the MHS engaged with the civilian sector during the COVID-19 pandemic and to elicit lessons for the future. Methods We conducted key informant interviews with MHS policymakers and advisers, program managers and providers who were affiliated with the MHS from March 2020 through December 2022. Key themes were derived using thematic analysis and open coding methods. Results We conducted 28 interviews between December 2022 and March 2023. During the pandemic, the MHS collaborated with federal and local healthcare authorities and private sector entities through endeavours such as Operation Warp Speed. Lessons and recommendations for future pandemics were also identified, including investment in biosurveillance systems and integration of behavioural and social sciences. Conclusions The MHS rapidly established and fostered key partnerships with the public and private sectors during the COVID-19 pandemic. The pandemic experience showed that while the MHS is a useful resource for the nation, it also benefits from partnering with a variety of organizations, agencies and private companies. Continuing to develop these partnerships will be crucial for coordinated, effective responses to future pandemics.

Abstract Background The Russian Federation’s invasion of Ukraine is characterized by indiscriminate attacks on civilian infrastructure, including hospitals and clinics that have devastated the Ukrainian health system putting trauma care at risk. International healthcare providers responded to the need for help with the increasing numbers of trauma patients. We aimed to describe their experiences during the conflict to explore the gaps in systems and care for trauma patients to refine the Global Trauma System Evaluation Tool (G-TSET) tool. Methods We conducted qualitative key informant interviews of healthcare providers and business and logistics experts who volunteered since February 2022. Respondents were recruited using purposive snow-ball sampling. Semi-structured, in-depth interviews were conducted virtually from January-March 2023 using a modified version of the G-TSET as an interview guide. Interviews were transcribed verbatim and deductive thematic content analysis was conducted using NVivo. Findings We interviewed a total of 26 returned volunteers. Ukraine’s trauma system is outdated for both administrative and trauma response practices. Communication between levels of the patient evacuation process was a recurrent concern which relied on handwritten notes. Patient care was impacted by limited equipment resources, such as ventilators, and improper infection control procedures. Prehospital care was described as highly variable in terms of quality, while others witnessed limited or no prehospital care. The inability to adequately move patients to higher levels of care affected the quality of care. Infection control was a key issue at the hospital level where handwashing was not common. Structured guidelines for trauma response were lacking and lead to a lack of standardization of care and for trauma. Although training was desired, patient loads from the conflict prohibited the ability to participate. Rehabilitation care was stated to be limited. Conclusion Standardizing the trauma care system to include guidelines, better training, improved prehospital care and transportation, and supply of equipment will address the most critical gaps in the trauma system. Rehabilitation services will be necessary as the conflict continues into its second year.

Decision makers in the behavioral health disciplines could benefit from tools to assist them in identifying and implementing evidence-based interventions. One tool is an evidence-based program resources website (EBPR). Prior studies documented that when multiple EBPRs rate an intervention, they may disagree. Prior research concerning the reason for such conflicts is sparse. The present study examines how EBPRs rate interventions and the sources of disagreement between EBPRs when rating the same intervention. This study hypothesizes that EBPRs may disagree about intervention ratings because they either use different rating paradigms or they use different studies as evidence of intervention effectiveness (or both). This study identified 15 EBPRs for inclusion. One author (M.J.L.E.) coded the EBPRs for which “tiers of evidence” each EBPR used to classify behavioral health interventions and which criteria they used when rating interventions. The author then computed one Jaccard index of similarity for the criteria shared between each pair of EBPRs that co-rated interventions, and one for the studies used by EBPR rating pairs when rating the same program. The authors used a combination of chi-square, correlation, and binary logistic regression analyses to analyze the data. There was a statistically significant negative correlation between the number of Cochrane Risk of Bias criteria shared between 2 EBPRs and the likelihood of those 2 EBPRs agreeing on an intervention rating ( r = −.12, P ≤ .01). There was no relationship between the number of studies evaluated by 2 EBPRs and the likelihood of those EBPRs agreeing on an intervention rating. The major reason for disagreements between EBPRs when rating the same intervention in this study was due to differences in the rating criteria used by the EBPRs. The studies used by the EBPRs to rate programs does not appear to have an impact.

BackgroundDue to variation in electrode design, insertion depth and cochlear morphology, patients with a cochlear implant (CI) often have to adapt to a substantial mismatch between the characteristic response frequencies of cochlear neurons and the stimulus frequencies assigned to electrode contacts. We introduce an imaging-based fitting intervention, which aimed to reduce frequency-to-place mismatch by aligning frequency mapping with the tonotopic position of electrodes. Results were evaluated in a novel trial set-up where subjects crossed over between intervention and control using a daily within-patient randomized approach, immediately from the start of CI rehabilitation.MethodsFourteen adult participants were included in this single-blinded, daily randomized clinical trial. Based on a fusion of pre-operative imaging and a post-operative cone beam CT scan (CBCT), mapping of electrical input was aligned to natural place-pitch arrangement in the individual cochlea. That is, adjustments to the CI’s frequency allocation table were made so electrical stimulation of frequencies matched as closely as possible with corresponding acoustic locations in the cochlea. For a period of three months, starting at first fit, a scheme was implemented whereby the blinded subject crossed over between the experimental and standard fitting program using a daily randomized wearing schedule, and thus effectively acted as their own control. Speech outcomes (such as speech intelligibility in quiet and noise, sound quality and listening effort) were measured with both settings throughout the study period.ResultsOn a group level, standard fitting obtained subject preference and showed superior results in all outcome measures. In contrast, two out of fourteen subjects preferred the imaging-based fitting and correspondingly had better speech understanding with this setting compared to standard fitting.ConclusionOn average, cochlear implant fitting based on individual tonotopy did not elicit higher speech intelligibility but variability in individual results strengthen the potential for individualized frequency fitting. The novel trial design proved to be a suitable method for evaluation of experimental interventions in a prospective trial setup with cochlear implants.

IntroductionEstimating differences in neural health across different sites within the individual cochlea potentially enables clinical applications for subjects with a cochlear implant. The electrically evoked compound action potential (ECAP) is a measure of neural excitability that possibly provides an indication of a neural condition. There are many factors, however, that affect this measure and increase the uncertainty of its interpretation. To better characterize the ECAP response, its relationship with electrode positioning, impedances, and behavioral stimulation levels was explored.MethodsA total of 14 adult subjects implanted with an Advanced Bionics cochlear electrode array were prospectively followed up from surgery to 6 months postoperative. Insertion depth, distance to the modiolus, and distance to the medial wall were assessed for each electrode by postoperative CT analysis. ECAPs were measured intraoperatively and at three visits postoperatively on all 16 electrodes using the NRI feature of clinical programming software and characterized using multiple parameters. Impedances and behavioral stimulation levels were measured at every fitting session.ResultsPatterns in ECAPs and impedances were consistent over time, but high variability existed among subjects and between different positions in the cochlea. Electrodes located closer to the apex of the cochlea and closer to the modiolus generally showed higher neural excitation and higher impedances. Maximum loudness comfort levels were correlated strongly with the level of current needed to elicit a response of 100 μV ECAP.ConclusionMultiple factors contribute to the ECAP response in subjects with a cochlear implant. Further research might address whether the ECAP parameters used in this study will benefit clinical electrode fitting or the assessment of auditory neuron integrity.

Goran Marković's Variola Vera (1982, Yugoslavia) is a film about a historic smallpox outbreak, which occurred in Yugoslavia in 1972. More importantly, it is a film about Yugoslav fear: a fear of the other, especially the oriental or Muslim other and thus of the ‘alien’ within. Variola Vera is also a film about the fear of society’s disintegration; on several levels it suggests that in 1982 (the idea of) Yugoslavia was more of a mirage produced for the international gaze than a Yugoslav reality. These collective fears are translated by the film into an epidemics narrative that works with topoi of the horror, disaster and science fiction genres. Furthermore, the film offers several ways out of the (not only medical) crisis which the epidemic brought to the fore: on the one hand, the crisis is fashioned as at least partially (re)awakening a self-sacrificial, revolutionary, partisan spirit of solidarity. On the other hand, humanist medical expertise returns in the guise of the uncanny to haunt the biopolitical measures introduced by the Yugoslav state apparatus. This article offers an in-depth analysis of the aforementioned neuralgic points brought forward by the variola epidemic, while inquiring into how in Marković’s rendering the disease itself became a complex symptom of the Yugoslav society of 1982.

Background: Sensory impairments commonly occur in patients with autism or intellectual disability. Fragile X syndrome (FXS) is one form of intellectual disability that is often comorbid with autism. In electroencephalographic (EEG) recordings obtained from humans with FXS, the ability of cortical regions to consistently synchronize, or “phase-lock”, to modulated auditory stimuli is reduced compared to that of typically developing individuals. At the same time, less time-locked, “non-phase-locked” power induced by sounds is higher. The same changes occur in the Fmr1 knockout (KO) mouse – an animal model of FXS. We determined if Fmr1 deletion in a subset of brainstem auditory neurons plays any role in these EEG changes in the mouse. Methods: We reinstated FMRP expression in a subpopulation of brainstem auditory neurons in an otherwise Fmr1 KO control (conditional on; cON Fmr1) mouse and used EEG recordings to determine if reinstatement normalized, or “rescued”, the phase-locking phenotype observed in the cON Fmr1 mouse. In determining rescue, this also meant that Fmr1 deletion in the same neuron population was necessary for the phenotype to occur. Results: We find that Fmr1 reinstatement in a subset of brainstem neurons rescues certain aspects of the phase-locking phenotype but does not rescue the increase in non-phase-locked power. Unexpectedly, not all electrophysiological phenotypes observed in the Fmr1 KO were observed in the cON Fmr1 mouse used for the reinstatement experiments, and this was likely due to residual expression of FMRP in these Fmr1 KO controls. Conclusions: Fmr1 deletion in brainstem neurons is necessary for certain aspects of the decreased phase-locking phenotype in the Fmr1 KO, but not necessary for the increase in non-phase-locked power induced by a sound. The most likely brainstem structure underlying these results is the inferior colliculus. We also demonstrate that low levels of FMRP can rescue some EEG phenotypes but not others. This latter finding provides a foundation for how symptoms in FXS individuals may vary due to FMRP levels and that reinstatement of low FMRP levels may be sufficient to alleviate particular symptoms.

Abstract A microscopic study of microplankton in two coastal lagoons in the Florida Keys coincidently, and unexpectedly, revealed the widespread presence of high concentrations of polystyrene microplastic particles. The polystyrene particles were first observed in the second year of a 2-year study of phytoplankton communities, with peak densities in the spring/summer of 2019 at all ten sampling sites in the two lagoons. Polystyrene particle densities reached levels up to 76,000 L−1. The particles ranged in size from 33 to 190 µm, similar to the size range of microplanktonic algae (20–200 µm). Over the period of peak polystyrene densities, average particle densities were similar to average densities of microplanktonic algae cells. The latter observation highlights the potential significance of the microplastic particles for the ecology of the pristine waters of the Florida Keys, if they persist.

Objective: This study aimed to identify differences in vestibulo-ocular reflex gain (VOR gain) and saccadic response in the suppression head impulse paradigm (SHIMP) between predictable and less predictable head movements, in a group of healthy subjects. It was hypothesized that higher prediction could lead to a lower VOR gain, a shorter saccadic latency, and higher grouping of saccades.Methods: Sixty-two healthy subjects were tested using the video head impulse test and SHIMPs in four conditions: active and passive head movements for both inward and outward directions. VOR gain, latency of the first saccade, and the level of saccade grouping (PR-score) were compared among conditions. Inward and active head movements were considered to be more predictable than outward and passive head movements.Results: After validation, results of 57 tested subjects were analyzed. Mean VOR gain was significantly lower for inward passive compared with outward passive head impulses (p < 0.001), and it was higher for active compared with passive head impulses (both inward and outward) (p ≤ 0.024). Mean latency of the first saccade was significantly shorter for inward active compared with inward passive (p ≤ 0.001) and for inward passive compared with outward passive head impulses (p = 0.012). Mean PR-score was only significantly higher in active outward than in active inward head impulses (p = 0.004).Conclusion: For SHIMP, a higher predictability in head movements lowered gain only in passive impulses and shortened latencies of compensatory saccades overall. For active impulses, gain calculation was affected by short-latency compensatory saccades, hindering reliable comparison with gains of passive impulses. Predictability did not substantially influence grouping of compensatory saccades.

The UK government announced in March 2020 that it would create an NHS Covid-19 ‘Data Store’ from information routinely collected as part of the health service. This ‘Store’ would use a number of sources of population data to provide a ‘single source of truth’ about the spread of the coronavirus in England. The initiative illustrates the difficulty of relying on automated processing when making healthcare decisions under the General Data Protection Regulation (GDPR). The end-product of the store, a number of ‘dashboards’ for decision-makers, was intended to include models and simulations developed through artificial intelligence. Decisions made on the basis of these dashboards would be significant, even (it was suggested) to the point of diverting patients and critical resources between hospitals based on their predictions. How these models will be developed, and externally validated, remains unclear. This is an issue if they are intended to be used for decisions which will affect patients so directly and acutely. We have (by default) a right under the GDPR not to be subject to significant decisions based solely on automated decision-making. It is not obvious, at present, whether resource allocation within the NHS could take place in reliance on this automated modelling. The recent A Level debacle illustrates, in the context of education, the risks of basing life-changing decisions on the national application of a single equation. It is worth considering the potential consequences for the health service if the NHS Data Store is used for resource planning as part of the Covid-19 response.

Objective: Comparing the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with the linear incision technique with soft tissue preservation (LITT-P) for bone conduction devices after a follow-up of 22 months.Methods: In this multicenter randomized controlled trial, there was the inclusion of 64 adult patients eligible for unilateral surgery. There was 1:1 randomization to the MIPS (test) or the LITT-P (control) group. The primary outcome was an (adverse) soft tissue reaction. Secondary outcomes were pain, loss of sensibility, soft tissue height/overgrowth, skin sagging, implant loss, Implant Stability Quotient measurements, cosmetic scores, and quality of life questionnaires.Results: Sixty-three subjects were analyzed in the intention-to-treat population. No differences were found in the presence of (adverse) soft tissue reactions during complete follow-up. Also, there were no differences in pain, wound dehiscence, skin level, soft tissue overgrowth, and overall quality of life. Loss of sensibility (until 3-month post-surgery), cosmetic scores, and skin sagging outcomes were better in the MIPS group. The Implant Stability Quotient was higher after the LITT-P for different abutment lengths at various points of follow-up. Implant extrusion was nonsignificantly higher after the MIPS (15.2%) compared with LITT-P (3.3%).Conclusion: The long-term results show favorable outcomes for both techniques. The MIPS is a promising technique with some benefits over the LITT-P. Concerns regarding nonsignificantly higher implant loss may be overcome with future developments and research.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02438618.

Seeking to move beyond Scott McCloud’s spatio-temporal reading of the bleed (1993: 103), this article explores how Canadian writer/artist Emily Carroll’s graphic narrative Through the Woods (2014) employs the bleed as a means to give form to a mode of horror known as the ‘abject’. Employing theories of embodiment that excavate historical conflations of femininity and nature, in addition to socio-cultural discourses that figure the female body as more uncontrollable than the male, this article explores the anxieties experienced by Carroll’s adolescent protagonists as they traverse the boundary separating girlhood from womanhood. By paying particular attention to Carroll’s excessive use of bleeds, this article argues that the stylistic convention of the bleed is utilised to adumbrate and illustrate the abject horror of such boundary crossings.

Informatics is becoming essential in our daily activities. The use of the human machine interface requires fine movements from the user. When human movements are distorted, for instance, by tremor, performance could be improved by digitally filtering the intermediate signal before it reaches the controlled interface. This paper presents a novel device able to filter out tremorous movements from the cursor of a mouse in the screen of the computer. This task requires real-time discrimination between voluntary and tremorous movement. To address this problem, a learning algorithm is introduced as well as the evaluation and validation with users of the prototype developed. [ABSTRACT FROM AUTHOR]

Current research into bacterial dynamics on the Greenland Ice Sheet (GrIS) is biased toward cryoconite holes, despite this habitat covering less than 8% of the ablation (melt) zone surface. In contrast, the expansive surface ice, which supports wide-spread Streptophyte micro-algal blooms thought to enhance surface melt, has been relatively neglected. This study aims to understand variability in bacterial abundance and production across an ablation season on the GrIS, in relation to micro-algal bloom dynamics. Bacterial abundance reached 3.3 ± 0.3 × 105 cells ml−1 in surface ice and was significantly linearly related to algal abundances during the middle and late ablation periods (R2 = 0.62, p < 0.05; R2 = 0.78, p < 0.001). Bacterial production (BP) of 0.03–0.6 μg C L−1 h−1 was observed in surface ice and increased in concert with glacier algal abundances, indicating that heterotrophic bacteria consume algal-derived dissolved organic carbon. However, BP remained at least 28 times lower than net primary production, indicating inefficient carbon cycling by heterotrophic bacteria and net accumulation of carbon in surface ice throughout the ablation season. Across the supraglacial environment, cryoconite sediment BP was at least four times greater than surface ice, confirming that cryoconite holes are the true “hot spots” of heterotrophic bacterial activity.

Introduction Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work. Approach We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research. Results We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered. Conclusions Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.

The aim of this study was to investigate the psychometric properties of the Foreign Language Classroom Anxiety Scale (FLCAS) for Cypriot senior high school EFL students, through Rasch measurement. In doing so, the researchers clarified two discrepancies found in the literature: first the factor structure of the scale and second whether test anxiety is a component of FLCA. The Greek version of the FLCAS was administered to a sample of 304 senior high school EFL students. Results showed that after removing five items which fitted the Rasch Rating Scale model poorly, the remaining 28 items formed a unidimensional scale, one component of which is test anxiety. The degree of reliability was high. Semantic analysis of the items revealed that one of the reasons was the inclusion of many parallel items. The Rasch person-item map showed that a second reason was the narrow coverage of the construct by the items. Finally the 5-point Likert scale was shown to be marginally optimal. Suggestions are proposed for future research into the refinement of the scale.

INTRODUCTION:Earlier studies show that a Cochlear Implant (CI), capable of providing intracochlear electrical stimulation independent of environmental sounds, appears to suppress tinnitus at least for minutes. The current main objective is to compare the long-term suppressive effects of looped (i.e. repeated) electrical stimulation (without environmental sound perception) with the standard stimulation pattern of a CI (with environmental sound perception). This could open new possibilities for the development of a "Tinnitus Implant" (TI), an intracochlear pulse generator for the suppression of tinnitus. MATERIALS AND METHODS:Ten patients with single sided deafness suffering from unilateral tinnitus in the deaf ear are fitted with a CI (MED-EL Corporation, Innsbruck, Austria). Stimulation patterns are optimized for each individual patient, after which they are compared using a randomized crossover design, with a follow-up of six months, followed by a 3 month period using the modality of patient's choice. RESULTS:Results show that tinnitus can be suppressed with intracochlear electrical stimulation independent of environmental sounds, even long term. No significant difference in tinnitus suppression was found between the standard clinical CI and the TI. CONCLUSION:It can be concluded that coding of environmental sounds is no requirement for tinnitus suppression with intracochlear electrical stimulation. It is therefore plausible that tinnitus suppression by CI is not solely caused by an attention shift from the tinnitus to environmental sounds. Both the standard clinical CI and the experimental TI are potential treatment options for tinnitus. These findings offer perspectives for a successful clinical application of the TI, possibly even in patients with significant residual hearing. TRIAL REGISTRATION:TrialRegister.nl NTR3374.

As Greek Cypriot senior high school teachers, the researchers believe that instruments assessing Internet addiction should be developed and validated for use wherever there are adolescents (the most at-risk population) and Internet access. The purpose of the study was to evaluate the psychometric properties of the Internet Addiction Test (IAT). A sample of 604 randomly selected high school students from five high schools in Limassol, Cyprus participated in the study. The Rasch Rating Scale Model was used for the analyses of the data collected. Results suggested the modification of the IAT in two ways. First, the 5-point rating scale was replaced by a 3-point scale, which was found to be optimal in the pilot study. Second, item 8 was replaced by a self-rating item because it was found to be identical to item 6 both statistically and semantically. The respondents’ reliability was satisfactory (0.86) and item reliability very high (0.99). All 20 items were sufficiently spread out and describe distinct levels along the variable and do define a linear continuum of increasing difficulty. All the evidence collected supports the unidimensionality and the high degree of construct validity of the scale. Finally four recommendations for the modification of the scale and future research are proposed.

O conceito de espaço socialmente organizado, subsidiado por novas técnicas de análise, mapeamento e espacialização da ocorrência de eventos, tem orientado desenvolvimentos metodológicos inovadores no campo das intervenções de saúde pública. Este estudo teve por objetivo avaliar a utilização de um indicador sócio-ambiental, construído através da metodologia de aplicação de escores, na estratificação do Município de Olinda, Pernambuco, em áreas com diferentes riscos de transmissão da filariose bancroftiana. Procedeu-se ao mapeamento das áreas, localização dos domicílios amostrados e identificação de todos os moradores com idade entre 5 e 65 anos para realização do inquérito parasitológico. Dentre as 3.232 pessoas examinadas, 42 foram positivas, obtendo-se prevalência de microfilaremia de 1,3%. A análise estatística global da distribuição dos casos mostrou evidências de agregação espacial. Nos dois estratos de mais alto risco de transmissão residiam 85,7% dos positivos. A alta sensibilidade do indicador proposto justifica a sua utilização para o planejamento e execução de intervenções ao predizer o local de ocorrência da maioria dos casos de filariose.

Abstract Background The increasing availability and diversity of omics data in the post-genomic era offers new perspectives in most areas of biomedical research. Graph-based biological networks models capture the topology of the functional relationships between molecular entities such as gene, protein and small compounds and provide a suitable framework for integrating and analyzing omics-data. The development of software tools capable of integrating data from different sources and to provide flexible methods to reconstruct, represent and analyze topological networks is an active field of research in bioinformatics. Results BisoGenet is a multi-tier application for visualization and analysis of biomolecular relationships. The system consists of three tiers. In the data tier, an in-house database stores genomics information, protein-protein interactions, protein-DNA interactions, gene ontology and metabolic pathways. In the middle tier, a global network is created at server startup, representing the whole data on bioentities and their relationships retrieved from the database. The client tier is a Cytoscape plugin, which manages user input, communication with the Web Service, visualization and analysis of the resulting network. Conclusion BisoGenet is able to build and visualize biological networks in a fast and user-friendly manner. A feature of Bisogenet is the possibility to include coding relations to distinguish between genes and their products. This feature could be instrumental to achieve a finer grain representation of the bioentities and their relationships. The client application includes network analysis tools and interactive network expansion capabilities. In addition, an option is provided to allow other networks to be converted to BisoGenet. This feature facilitates the integration of our software with other tools available in the Cytoscape platform. BisoGenet is available at http://bio.cigb.edu.cu/bisogenet-cytoscape/.

Abstract Background Sub-national analyses of causes of death and time-trends help to define public health policy priorities. They are particularly important in countries undergoing epidemiological transition like Peru. There are no studies exploring Peruvian national and regional characteristics of such epidemiological transition. We aimed to describe Peru's national and regional mortality profiles between 1996 and 2000. Methods Registered mortality data for the study period were corrected for under-registration following standardized methods. Main causes of death by age group and by geographical region were determined. Departmental mortality profiles were constructed to evaluate mortality transition, using 1996 data as baseline. Annual cumulative slopes for the period 1996–2000 were estimated for each department and region. Results For the study period non-communicable diseases explained more than half of all causes of death, communicable diseases more than one third, and injuries 10.8% of all deaths. Lima accounted for 32% of total population and 20% of total deaths. The Andean region, with 38% of Peru's population, accounted for half of all country deaths. Departmental mortality predominance shifted from communicable diseases in 1996 towards non-communicable diseases and injuries in 2000. Maternal and perinatal conditions, and nutritional deficiencies and nutritional anaemia declined markedly in all departments and regions. Infectious diseases decreased in all regions except Lima. In all regions acute respiratory infections are a leading cause of death, but their proportion ranged from 9.3% in Lima and Callao to 15.3% in the Andean region. Tuberculosis and injuries ranked high in Lima and the Andean region. Conclusion Peruvian mortality shows a double burden of communicable and non-communicable, with increasing importance of non-communicable diseases and injuries. This challenges national and sub-national health system performance and policy making.

José Luis López-Campos,1,2 Bernardino Alcázar Navarrete,3 Juan Antonio Riesco Miranda,2,4 Borja G Cosío,2,5 Juan P de-Torres,6 Bartolomé Celli,7 Carlos A Jiménez-Ruiz,8 Ciro Casanova Macario9 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Sevilla, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Hospital de Loja, Loja, Granada, Spain; 4Hospital Universitario de Cáceres, Cáceres, Spain; 5Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 6Respirology Division, Queen’s University, Kingston, ON, Canada; 7Brigham and Women’s Hospital, Harvard Medical School Boston, Boston, MA, USA; 8Unidad Especializada en Tabaquismo, Hospital Clínico San Carlos, Madrid, Spain; 9Servicio de Neumología-Unidad de Investigación, Hospital Universitario La Candelaria, Universidad de La Laguna, La Laguna, SpainCorrespondence: José Luis López-CamposHospital Universitario Virgen del Rocio, Avda. Manuel Siurot, S/N, Sevilla 41013, SpainTel +34955013166Email lcampos@separ.esIntroduction: Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain.Methods: A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥ 80% of the panelists agreed; a majority when a degree of agreement of ≥ 66% was reached; and divergence if agreement was < 66%.Results: After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity.Conclusion: The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.Keywords: chronic obstructive pulmonary disease, LABA/LAMA, LABA/ICS, bronchodilator agents, inhaled corticosteroids, triple therapy, statements, Delphi consensus

Introduction: We have carried out a systematic review of the literature (SRL) and a meta-analysis (MA) to answer: 1. Validity of the nicotine metabolite ratio (NMR) in improving the effectiveness of pharmacological treatments (PT) for smoking cessation (SC). 2. Validity of the NMR to improve the safety of the use of these PT? and 3. Validity of NMR in improving adherence to these PT?, Method: We carried out an SRL (six databases) and an MA for responding to the questions., Results: PT for SC (any treatment) is more effective in smoking subjects with slow NMR compared with fast NMR. Varenicline (VR) is equally effective in fast and slow NMR (RR 1.04 [CI 95% 0.75, 1.44]). When we compared those smokers who were treated to quit smoking with VR or nicotine replacement therapy (NRT) in fast metabolizers, we found that abstinence was in favor of those who were treated with VR (RR 1.40 [CI 95% 1.02, 1.91]). Those who were treated to quit smoking with NRT presented better results in slow Metabolizers (RR 0.70 [CI 95% 0.58, 0.83]). NMR increases the safety and adherence of treatments., Conclusions: We suggest that NMR is a good biomarker in the personalization of smoking cessation.

The increase of anthropogenic CO 2 in the Earth's atmosphere reduces the pH and raises the temperature of the oceans. The combination of both factors impacts the physiological responses and calcium carbonate structures of marine organisms. This study assessed the performance of the juvenile stage of the gastropod Acanthina monodon, after it was continuously exposed to treatments at two pCO 2 levels (400 and 1200 μatm) at two temperatures (10 °C and 15 °C) during the periods of embryonic encapsulated development and the early post-hatching juvenile stage. Juvenile performance was evaluated by quantifying shell growth, survival, foot adhesion strength, shell breakage resistance, and oxygen consumption rates. The results indicate that the combination of increased temperature and decreased pH increased juvenile shell growth, while only the decrease in pH had a negative effect on shell strength. However, juveniles were able to attach more strongly to substrates following exposure to the higher temperature level. Furthermore, the interaction of treatments had no effect on the metabolic rate or survival of juveniles, suggesting a possible compensatory effect of the juveniles to the more adverse conditions to which they were exposed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Evaluating the mutagenic properties of chemicals is crucial for understanding their potential cancer risks. Recent Illumina-based error-corrected sequencing techniques have enabled the direct detection of mutations induced de novo by mutagens. However, as the Illumina platform lacks intrinsic error-correction capabilities, complex library preparations and bioinformatic processes are necessary to identify these rare mutations. In this study, we evaluated whether long-read PacBio-based HiFi sequencing (HiFi seq), which has integrated error-correction, can detect de novo mutations induced by mutagens in C57BL/6 mouse tissues. Using HiFi seq, dose-dependent increases in mutation frequencies were found in tissues from mice exposed to 7,12-dimethylbenz[a]anthracene, procarbazine, and N-propyl-N-nitrosourea. Furthermore, the mutational signatures derived from these exposures were consistent with those previously reported for these mutagens. This study demonstrates that HiFi seq can complement established mutation detection assays to facilitate the identification of hazardous compounds., (Published by Oxford University Press on behalf of the Society of Toxicology 2024.)

The estuarine anemone Anthopleura hermaphroditica and its symbiont Philozoon anthopleurum are continuously exposed to intense fluctuations in solar radiation and salinity owing to tidal changes. The aim of this study was to evaluate the effects of the tidal cycle, solar radiation, and salinity fluctuations on the photosynthetic and cellular responses (lipid peroxidation, total phenolic compounds, and antioxidant activity) of the symbiont complex over a 24 h period in the Quempillén River Estuary. Additionally, laboratory experiments were conducted to determine the specific photobiological responses to photosynthetically active radiation (PAR), ultraviolet radiation (UVR), and salinity. Our field results showed that the photosynthetic parameters of the symbiont complex decreased with increasing ambient radiation; however, no relationship was observed with changes in salinity. Increased peroxidative damage, total phenolic compound levels, and antioxidant activity were mainly related to increased UVR and, to a lesser extent, PAR. During the dark period, only PAR-exposed organisms returned to the basal levels of photosynthesis and cell damage. Laboratory exposure confirmed the deleterious effects of UVR on the photosynthetic response. The present study suggests that the ability of A. hermaphroditica to acclimate to natural radiation stress is mediated by the concerted action of various physiological mechanisms that occur at different times of the day, under varying levels of environmental stress.

We report here the complete genome sequence of cephalosporin (cefazolin and cephalotin) and tetracycline-resistant Citrobacter freundii strain CF51, isolated from a patient with a urinary tract infection. The genome comprises a 5.0-Mb chromosome, along with an 87.2-kb plasmid and a 23.9-kb plasmid., Competing Interests: The authors declare no conflict of interest.

The influx of volcanic ash into seawater alters particle composition with implications for the cellular, physiological and anatomical response of suspension-feeding organisms. Adult females of Crepipatella peruviana were exposed to three diets consisting of a fixed concentration of 50,000 cells ml -1 of the microalga Isochrysis galbana plus different concentrations of ash particles (30, 90 and 150 mg L -1 ). The objective was to determine the cellular, physiological and anatomical responses. Mortality increased with ash concentrations, while feeding and respiration rates, tissue weight, and condition index decreased. The gills showed severe degradation of cilia and the presence of large mucous aggregates of cilia and ash. An increase in ash resulted in decreased lipid peroxidation and protein carbonyls, but increased total antioxidant capacity and phenols. Thus, volcanic ash particles may exert a high impact at both cellular and physiological levels for C. peruviana, where inhibition of gill function reduces the ability to acquire food., 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.)

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is alarmingly increasing alongside the cases of obesity worldwide. MASLD is an underestimated metabolic abnormality closely linked with a higher risk of developing systemic arterial hypertension (SAH). However, the underlying mechanism of association between MASLD and SAH remains unknown. Inflammation may link these two entities by regulating the renin-angiotensin system (RAS). For this reason, in this study, we evaluated the hepatic expression of a cytokine profile and critical molecules in the RAS pathway in patients with morbid obesity and MASLD, both with SAH. We found a statistically significant correlation between ACE levels and the cytokines IL-4, IL-10, and IL-13 of Th2 response. Furthermore, according to a multiple linear regression analysis, the cytokines IL-4 and IL-13 were the best predictors of ACE levels. Moreover, we observed increased hepatic IL-13 expression in patients with morbid obesity, MASLD, and SAH compared to those without SAH. These results allow us to propose, for the first time, that the Th2 response, through regulating the RAS, could play a critical role in developing SAH in individuals with MASLD and obesity.

For sessile intertidal organisms, periods of low tide impose both cellular and physiological challenges that can determine bathymetric distribution. To understand how intertidal location influences the cellular response of the bivalve Perumytilus purpuratus during the tidal cycle (immersion-emersion-immersion), specimens from the upper intertidal (UI) and lower intertidal (LI) of bathymetric distribution were sampled every 2 h over a 10-h period during a summer tidal cycle. Parallelly, organisms from the UI and LI were reciprocally transplanted and sampled throughout the same tidal cycle. Levels of oxidative damage (lipid peroxidation and protein carbonyls) as well as total antioxidant capacity and total carotenoids were evaluated as cellular responses to variations in environmental conditions throughout the tidal cycle. The results indicate that both the location in the intertidal zone (UI/LI), the level of aerial exposure, and the interaction of both factors are determinants of oxidative levels and total antioxidant capacity of P. purpuratus. Although oxidative damage levels are triggered during the low tide period (aerial exposure), it is the UI specimens that induce higher levels of lipid peroxidation compared to those from the LI, which is consistent with the elevated levels of total antioxidant capacity. On the other hand, organisms from the LI transplanted to the UI increase the levels of lipid peroxidation but not the levels of protein carbonyls, a situation that is also reflected in higher levels of antioxidant response and total carotenoids than those from the UI transplanted to the LI. The bathymetric distribution of P. purpuratus in the intertidal zone implies differentiated responses between organisms of the lower and upper limits, influenced by their life history. A high phenotypic plasticity allows this mussel to adjust its metabolism to respond to abrupt changes in the surrounding environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Azamethiphos is used in the salmon industry to treat sea lice and is subsequently discharged into the sea, which may affect non-target species (NTS). A rise in seawater temperature could enhance the sensitivity of NTS. Thus, in the present investigation, the combined effects of azamethiphos (0 µg L -1 , 15 µg L -1 and 100 µg L -1 ) and temperature (12 °C and 15 °C) was assessed over time (7 days) in the gonads and gills of the oyster Ostrea chilensis , assessing its oxidative damage (lipid peroxidation and protein carbonyls) and total antioxidant capacity. Our results indicated that in gonads and gills, lipid peroxidation levels increased over time during exposure to both pesticide concentrations. Protein carbonyl levels in gills increased significantly in all experimental treatments; however, in gonads, only pesticide concentration and exposure time effected a significant increase in protein damage. In both, gill and gonad temperature did not influence oxidative damage levels. Total antioxidant capacity in gonads was influenced only by temperature treatment, whereas in the gills, neither temperature nor azamethiphos concentration influenced defensive responses. In conclusion, our results indicated the time of pesticide exposure (both concentrations) had a greater influence than temperature on the cellular damage in this oyster.

We analyzed antimicrobial resistance and virulence traits in multidrug-resistant (MDR) E. coli isolates obtained from imported shrimp using whole-genome sequences (WGSs). Antibiotic resistance profiles were determined phenotypically. WGSs identified key characteristics, including their multilocus sequence type (MLST), serotype, virulence factors, antibiotic resistance genes, and mobile elements. Most of the isolates exhibited resistance to gentamicin, streptomycin, ampicillin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. Multilocus sequence type (MLST), serotype, average nucleotide identity (ANI), and pangenome analysis showed high genomic similarity among isolates, except for EC15 and ECV01. The EC119 plasmid contained a variety of efflux pump genes, including those encoding the acid resistance transcriptional activators ( gadE , gadW , and gadX ), resistance-nodulation-division-type efflux pumps ( mdtE and mdtF ), and a metabolite, H1 symporter (MHS) family major facilitator superfamily transporter ( MNZ41&#95;23075 ). Virulence genes displayed diversity, particularly EC15, whose plasmids carried genes for adherence ( faeA and faeC-I ), invasion ( ipaH and virB ), and capsule ( caf1A and caf1M ). This comprehensive analysis illuminates antimicrobial resistance, virulence, and plasmid dynamics in E. coli from imported shrimp and has profound implications for public health, emphasizing the need for continued surveillance and research into the evolution of these important bacterial pathogens.

Background:  Gait disturbances are prevalent and debilitating symptoms, diminishing mobility and quality of life for Parkinson's disease (PD) individuals. While traditional treatments offer partial relief, there is a growing interest in alternative interventions to address this challenge. Recently, a remarkable surge in assisted technology (AT) development was witnessed to aid individuals with PD., Objective:  To explore the burgeoning landscape of AT interventions tailored to alleviate PD-related gait impairments and describe current research related to such aim., Methods:  In this review, we searched on PubMed for papers published in English (2018-2023). Additionally, the abstract of each study was read to ensure inclusion. Four researchers searched independently, including studies according to our inclusion and exclusion criteria., Results:  We included studies that met all inclusion criteria. We identified key trends in assistive technology of gait parameters analysis in PD. These encompass wearable sensors, gait analysis, real-time feedback and cueing techniques, virtual reality, and robotics., Conclusion:  This review provides a resource for guiding future research, informing clinical decisions, and fostering collaboration among researchers, clinicians, and policymakers. By delineating this rapidly evolving field's contours, it aims to inspire further innovation, ultimately improving the lives of PD patients through more effective and personalized interventions., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background and Objectives : Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods : We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild ( n = 7), moderate ( n = 19), or severe ( n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results : The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group ( p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( p = 0.005 and p < 0.0001, respectively). Conclusions : In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Sunscreen products are essential for shielding the skin from ultraviolet (UV) radiation, a leading cause of skin cancer. While existing products serve this purpose, there is a growing need to enhance their efficacy while minimizing potential systemic absorption of UV filters and associated toxicological risks. Liposomal-based formulations have emerged as a promising approach to address these challenges and develop advanced photoprotective products. These vesicular systems offer versatility in carrying both hydrophilic and lipophilic UV filters, enabling the creation of broad-spectrum sunscreens. Moreover, their composition based on phospholipids, resembling that of the stratum corneum, facilitates adherence to the skin's surface layers, thereby improving photoprotective efficacy. The research discussed in this review underscores the significant advantages of liposomes in photoprotection, including their ability to limit the systemic absorption of UV filters, enhance formulation stability, and augment photoprotective effects. However, despite these benefits, there remains a notable gap between the potential of liposomal systems and their utilization in sunscreen development. Consequently, this review emphasizes the importance of leveraging liposomes and related vesicular systems as innovative tools for crafting novel and more efficient photoprotective formulations.