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Background: Hallux valgus is a deformity characterized by lateral deviation of the big toe and medial deviation of the first metatarsal, causing difficulty in walking and requiring various treatments. Despite its multifactorial etiology, the role of the tibialis anterior tendon in hallux valgus and its variations in the morphology of tibialis anterior tendon distal insertion sites have not been fully explored. This study aimed to evaluate the effect of such variations on hallux valgus using magnetic resonance imaging., Methods: This was a retrospective study and included 115 individuals aged 18 years and older who underwent foot radiographs and MRI. The participants were divided into a hallux valgus group of 53 patients and a control group of 62 people based on radiographic measurements. Tibialis anterior tendon distal attachment was classified into five types according to the attachment morphology. Statistical analyses were performed to evaluate the relationship between the tibialis anterior tendon types and hallux valgus severity., Results: Among the participants, patients who underwent foot radiography and MRI due to any medical indication 70.4% were female, with a mean age of 43.83 ± 15.25 years. In terms of tibialis anterior tendon distal attachment, the most common type was Type 5 (40.9%), followed by Type 2 (34.8%). Type 4 was not observed in any case. In all participants, the mean hallux valgus angle was 20.63 ± 8.42 o , and the mean intermetatarsal angle was 9.69 ± 2.68 o . Tibialis anterior tendon distal attachment Type 5 was significantly associated with an increased hallux valgus angle but not with the intermetatarsal angle. We found a significant relationship between the diameter of the tibialis anterior tendon and hallux valgus angle., Conclusions: This study revealed a significant association between hallux valgus and Type 5 tibialis anterior tendon distal attachment, suggesting that tibialis anterior tendon morphology influences hallux valgus severity. The findings underscore the importance of considering variations in tibialis anterior tendon distal attachment sites in the etiopathogenesis and treatment planning of hallux valgus., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for this study was obtained from Kastamonu University Clinical Research Ethics Committee on February 7, 2024, (no. 2024-KAEK-19). All methods were performed in accordance with the 1964 Declaration of Helsinki and its later amendments, and the ethical standards of the institutional research committee. Consent for publication: Written informed consent for publication was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The ergonomic advantages and potential challenges that robotic surgery poses to the well-being of surgeons are mainly unexplored. The most recent surgical robot introduced on the European market is the Hugo™ RAS System by Medtronic. This study aims to evaluate the ergonomic benefits of the Hugo™ RAS System, which is available in our training laboratory, CeMIT (Center for Medical Innovation and Technology Cologne)., Methods and Procedures: Using the previously established Cologne Ergonomic Measurement Setup for Robotic Surgery (CEMRobSurg), we measured three parameters related to ergonomic posture from subjects with different levels of surgical expertise (laypeople, medical students, surgical residents, and expert robotic surgeons). The heart rate was measured continuously using a polar band. The noise level was measured while using the Hugo™ RAS System, and automated photographs using our locally developed methodology were captured of the participant every 2 s to assess body posture. The ergonomic measurements were conducted while the subject performed the same standardized robotic training exercises (Peg Board, Rope Walk, and Ring Walk)., Results: A total of 53 participants were enrolled in this study. The average noise level during all measurements was 54.87 dB. The highest stress level was measured in surgical residents with a sympathetic nervous system index (SNS index) of 1.15 (min - 1.43, max 3.56). The lowest stress level was measured in robotic experts with an SNS index of 0.23 (min - 0.18, max 0.91). We observed a risk-prone positioning of the neck and elbow in medical students (mean 39.6° and 129.48°, respectively). Robotic experts showed a risk positioning in the knee and hip region (mean 107.89° and 90.31°, respectively)., Conclusion: This is the first study to analyze and objectify the ergonomic posture of medical students, surgical trainees, surgeons, and laypeople using the open console, modular Hugo™ RAS System. Our findings offer recommendations for operating surgeons and allow for a comparative analysis between the different robotic systems. Further evaluations in real-time operative scenarios will follow., (© 2024. The Author(s).)

The animal nature of human beings has all but disappeared from psychoanalytic discourse. This reflects Freud's struggle with the issue of animality, which he at once repudiates, and simultaneously conceals at the core of human mental life. Freud's use of the terms "animal" and "man" constantly shifts as he attempts to employ them in key areas of analytic theory building, while also shifting his perspective along the way to consider the opposition, similarity and identity of these terms. This impedes attempts to find structure and coherence in Freud's view, which is almost liquid in its instability. For Freud what separates man from the animal world does not rely upon the evolutionary or anthropological arguments he makes, but on a process of identification and disidentification that consigns animality to "not-me" states in support of Oedipal resolution. Ultimately, his attempts to bind and tame human animality via Oedipality cannot contain that which was never separate and could never be separated from the human.

Achieving global restoration targets poses challenges including the need for long-term research and effective monitoring of success, fostering collaborations across diverse fields and actors, ensuring the availability of suitable reference ecosystems, and securing sustained funding. Yet, these conditions are often lacking, limiting the effectiveness of restoration. We provide an overview of ecological restoration practices in the pan-European region of the Long-term Ecological Research Network (eLTER) and demonstrate the importance of eLTER and its potential contributions to support the implementation of the EU Nature Restoration Law. We developed an online questionnaire to collect information on eLTER restoration experts and restoration projects details including the use of eLTER contributions (e.g. infrastructure, data and knowledge), between November 2021 and March 2022. We identified 62 restoration experts and 42 restoration projects from 18 countries. Our results show that eLTER restoration expertise covers most of the European habitats, diverse degradation states and restoration techniques. Most restoration projects (78%) involved long-term monitoring exceeding the average project lifespan, which has proven necessary to achieve restoration success. No common protocol was used for monitoring and evaluation or cost-benefit estimates, but respondents reported effective projects, mostly financed from national funds, and benefits in five ecosystem services on average covered per project. Key eLTER contributions included providing reference ecosystems, biotic and abiotic background data, and interdisciplinary discussion or stakeholder management. Ecological restoration is time intensive and requires long-term research and monitoring standardization to fully understand the restoration process and to ensure comparability across ecosystems. The eLTER network can help address these challenges providing added-value contributions through its infrastructure, long-term datasets, diversity of expertise and strategies that can help identify best restoration practices and support the EU Nature Restoration Law. Finally, additional and long-term funding from the EU and the private sector is needed to achieve global larger-scale restoration targets., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL - 1 , 0.1 mg mL - 1 , 1.0 mg mL - 1 , 10.0 mg mL - 1 , 100.0 mg mL - 1 , and 1,000.0 mg mL - 1 . To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite the clinical validation and unequivocal benefit to patients, the development of cancer immunotherapies is facing some key challenges and the attrition rate in early phases of development remains high. Identifying the appropriate patient population that would benefit most from the drug is on the critical path for successful clinical development. We believe that a systematic implementation of patient enrichment strategies early in the drug development process and trial design, is the basis for an innovative, more efficient, and leaner clinical development to achieve earlier a clear proof of concept or proof of failure. In this position article, we will describe and propose key considerations for the implementation of patient enrichment strategies as an opportunity to provide decision-enabling data earlier in the drug development process. We introduce an innovative multidimensional tool for immuno-oncology drug development that focuses on facilitating the identification and prioritization of enrichment-relevant biomarkers, based on the drug mechanism of action. To illustrate its utility, we discuss patient enrichment examples and use a case in the field of cancer immunotherapy, together with technical and regulatory considerations. Overall, we propose to implement fit for purpose enrichment strategies for all investigational drugs as early as possible in the development process. We believe that this will increase the success rate of immuno-oncology clinical trials, and eventually bring new and better medicines to patients faster., (©2023 American Association for Cancer Research.)

Objectives: State-level abortion bans in the United States have created a complex legal landscape that forces many prospective patients to travel long distances to access abortion care. The financial strain and logistical difficulties associated with travelling out of state for abortion care may present an insurmountable barrier to some individuals, especially to those with limited resources. Tracking the impact of these abortion bans on travel and housing is crucial for understanding abortion access and economic changes following the Dobbs U.S. Supreme Court decision., Study Design: This study used occupancy data from an average of 2,349,635 (standard deviation = 111,578) U.S. Airbnb listings each month from October 1st, 2020, through April 30th, 2023, to measure the impact of abortion bans on travel for abortion care and the resulting economic effects on regional economies., Methods: The study used a synthetic difference-in-differences design to compare monthly-level occupancy rate data from 1-bedroom entire-place Airbnb rentals within a 30-min driving distance of abortion clinics in states with and without abortion bans., Results: The study found a 1.4 percentage point decrease in occupancy rates of Airbnbs around abortion clinics in states where abortion bans were in effect, demonstrating reductions in Airbnb use in states with bans. In the 6-month period post Dobbs, this decrease translates to 16,548 fewer renters and a $1.87 million loss in revenue for 1-bedroom entire-place Airbnbs within a 30-min catchment area of abortion facilities in states with abortion restrictions., Conclusion: This novel use of Airbnb data provides a unique perspective on measuring demand for abortion and healthcare services and demonstrates the value of this data stream as a tool for understanding economic impacts of health policies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Downregulation of MHC class I expression and/or defects in the antigen presentation pathways are commonly reported in human cancers. Numerous studies previously have explored extensively the molecular mechanisms that underlie HLA-class I and Beta2-Microglobulin (B2M) downregulation. However, the techniques presently available to detect expression of MHC class I proteins lack the robustness, specificity and sensitivity needed for systematic integration and analysis in clinical trials. Furthermore, the dynamics of HLA-class I and B2M expression have not been comprehensively studied as a potential biomarker for immunotherapy., Methods: Using novel, validated, immunohistochemistry (IHC)-based methods for quantifying B2M and HLA-A in tumor samples from diverse cancer types, we have determined loss of B2M and HLA-A proteins in 336 archived, primary specimens and 329 biopsies from metastatic patients collected during Roche-sponsored Phase 1 clinical trials investigating novel immunotherapy candidates as monotherapy or in combination with CPI., Results: Up to 56% of cases with B2M or HLA-A loss were noted in the investigated tumor types. The frequency of loss was dependent on indication and stage of disease and revealed heterogeneous expression patterns across patients. B2M and HLA-A loss was increased in metastatic lesions compared to primary tumors, indicating selection of MHC class I low clones in metastatic and refractory tumor cells. High on-treatment B2M expression correlated with successful clinical outcome (RECIST), while high baseline B2M did not. A treatment-induced increase of B2M expression was noted in most of the patients with low B2M levels at baseline. The triple biomarker combination of B2M, CD8 and PDL1 strongly improved response prediction to cancer immunotherapy., Conclusion: Our results indicate that B2M and HLA-A loss occurs frequently in tumors and is reversed in most instances following immunotherapy which supports the conclusion that MHC class I loss is not the dominant resistance mechanism to CPI treatment. This investigation reveals a highly dynamic expression of HLA-A and B2M in tumors affected by indication, metastatic status, immunophenotype and immunotherapy treatment. Baseline expression levels of B2M on tumors may be of utility as a constituent of a biomarker panel used for selecting patients for immunotherapy clinical trials., Competing Interests: The authors are Roche employees. BR, BG, JA, SD, AH, NR own F. Hoffmann-La Roche Ltd. shares., (Copyright © 2024 Reis, Attig, Dziadek, Graefe, Heller, Rieder and Gomes.)

Introduction: Nutrition is a cornerstone of diabetes mellitus prevention and management; therefore, it is essential to enable patients to adopt healthy eating habits. Previous studies have not yet documented the main errors in the eating habits of Portuguese people with type 2 diabetes mellitus. This study aims to identify the main errors in the eating habits of people living with type 2 diabetes mellitus in Portugal and to evaluate its associations with sociodemographic variables., Methods: Cross-sectional multicentric study in a convenience sample of people with type 2 diabetes mellitus in Primary Health Care Units. The UK Diabetes and Diet Questionnaire (UKDDQ) - translated and adapted, was applied from July to October 2022. Descriptive and inferential statistical analyses were conducted., Results: Of the 550 participants, 52.2% were female, 68.3% were 65 years or over, 55.8 % had an education level up to the fourth grade, 24.7% had economic deprivation, and the mean time since diagnosis was 10.60 ± 8.13 years. Only 36.2% of the sample had a healthy UKDDQ score. Less than 50% of the sample had healthy scores for the items "high-fiber rice or pasta", "high-fiber bread", "butter, margarine and vegetable oils" and "vegetables and pulses". Only 8.9% of the sample had a healthy consumption of fiber. About 70.4% reported healthy scores for the consumption of "high-added-sugar foods" and 54.7% for "high-saturated fat". A statistically significant weak positive correlation was found between the UKDDQ score and age (ρ = 0.201, p < 0.001) with a more frequent choice of healthy foods with increasing age. Female respondents reported healthier habits, particularly in the consumption of "high-saturated fat" and "high-fiber foods"., Conclusion: The majority of our sample did not take advantage of the potential benefits of healthy eating habits. The main food groups whose consumption should be emphasized or discouraged were individualized, particularly the need to encourage the consumption of high-fiber foods. Targeted educational actions must focus especially on younger and/or male patients.

Analysts seem spellbound by language when it comes to the word interpretation , a word so idealized and grand, so laden with fantasy, that the term itself continues to hold a magical sense that defies us to think about it. Called upon to do far too much explanatory work in psychoanalysis, it is accorded a variety of meanings. It is employed for varied uses, often simultaneously, making it hard to know what analysts mean when referring to "interpretation" and what uses they intend for it. Approaches to interpretation may be heuristically separated into those having to do with the content of the unconscious and those attempting to "use" interpretation in a manner still not divorced from content. What it means to attempt to interpret what is by definition uninterpretable is yet another area to be explored. Accordingly, issues of construction, co-construction, and transformation are examined. Every interpretation is at once a concealment, every inscription a negation, every representation a re-presentation of something unrepresentable. Despite this, the concept of interpretation, even if theoretically unsupportable in large measure, retains its clinical utility.

The purpose of this study was to investigate the potential of using ruminal pH measurements to track time-series ruminal volatile fatty acid (VFA) concentrations occurring in response to short-term dietary disruption. Four ruminally cannulated dry Holstein dairy cows were individually housed and assigned to 4 treatments in a Latin square design. Treatments differing in forage-to-concentrate (F:C) ratio (100:0 to 55:45) were used because they were expected to result in large differences in VFA concentration, over which the relationships between pH and VFA could be robustly evaluated. Each sampling period lasted 36 h. Animals were removed from pasture and fasted for 24 h, after which time they were fed their treatment ration for 2 h and sampled for rumen fluid hourly for 12 h. Rumen fluid samples were analyzed immediately for pH, frozen, and subsequently analyzed for VFA concentrations using gas chromatography. Animals were returned to pasture for 7 d between sampling periods. To confirm that the short-term dietary disruptions resulted in expected variation in VFA concentrations, mean VFA concentrations during each animal period (n = 16) were analyzed using a linear mixed effects model with fixed (linear and quadratic) effects for F:C ratio and random effects for animal and period. Results indicated significant changes in VFA concentration across F:C ratio, but no significant shifts in VFA molar proportions, perhaps due to the short-term nature of the feeding protocol. To explore opportunity to use pH measurements to explain variability in VFA concentrations in real time across dietary conditions, a linear mixed-effect model was used to link the time-series measurements (n = 207). The VFA concentrations were analyzed with linear mixed effect models using linear and quadratic terms for pH, and random effects for animal and period. These models had poor accuracy, with residual error variance ranging from 21% to 38%, and residuals patterning significantly with F:C ratio. The data suggest that pH may lack reliability for VFA prediction in short-term feeding scenarios differing considerably in F:C ratio., (© 2023.)

Many sources of pollution that are generated by modern society are not addressable by conventional methods. Especially organic compounds, like pharmaceutics, are particularly hard to remove from waterbodies. Herein, a new approach is presented using conjugated microporous polymers (CMPs) to coat silica microparticles yielding specifically tailored adsorbents. The CMPs are generated with three different monomers: 2,6-dibromonaphthalene (DBN), 2,5-dibromoaniline (DBA) and 2,5-dibromopyridine (DBPN) respectively coupled to 1,3,5-triethynylbenzene (TEB) via Sonogashira coupling. By optimizing the polarity of the silica surface, all three CMPs were converted into microparticle coatings. The resulting hybrid materials feature the advantages of being adjustable in polarity and functionality, as well as morphology. Sedimentation allows facile removal of the coated microparticles after the adsorption. Further, the expansion of the CMP to a thin coating increases the accessible surface area compared to the bulk material. These effects were demonstrated by the adsorption of the model drug diclofenac. Thereby, the aniline-based CMP proved to be most advantageous due to a secondary crosslinking mechanism of amino and alkyne functionalities. An outstanding adsorption capacity of 228 mg diclofenac per gram of the aniline CMP within the hybrid material was achieved. This represents a five-fold increase compared to the value obtained by the pure CMP material underlining the advantages of the hybrid material., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aim of this technical note is to describe a protocol for three-dimensional virtual simulation of orthognathic surgery that has been designed to be easily implemented, without the need for any special clinical apparatus, software brand, or computed tomography sequence. The protocol comprises innovative concepts and simplified steps for image segmentation, creation of a composite skull, control of the condylar position, and sequencing of bimaxillary surgery. This protocol was applied by the developers in about 2000 cases performed between 2015 and 2022, and has become quite popular among local surgeons. Previous preliminary studies have shown that it meets the accuracy standards for clinical use, although further studies with larger numbers of patients are desirable for additional validation., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms., Methods: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built., Results: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression., Conclusion: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypothesis: High nitrogen containing resins such as poly(melamine-co-formaldehyde) (PMF) are known for their very good adsorption properties. Until now, using an ecofriendly hard-templating approach with SiO 2 nanospheres in water for synthesis, only yielded either highly porous particles with diameters up to 1 µm or non-porous particles with diameters above 1 µm. Small particles cannot be used as fixed bed adsorbents in columns because of the very high pressure occurring., Experiments: To yield particles with high porosity and larger diameters for the use as fixed bed adsorbent, we investigated the influence of several synthesis parameters on porosity and particle morphology., Findings: From all variations, we proposed a mechanism for the complex interplay between the PMF prepolymer and resin species with SiO 2 nanoparticles acting both as Pickering-like surfactant and template particle. With this knowledge we were able to produce a suitable column material with high specific surface area up to 260 m 2 /g. We then proved the application of this material for aqueous dichromate adsorption in batch, yielding a maximum capacity of 138 mg/g with recyclability. In column experiments, the contamination of 5 mg/L dichromate in water was reduced to drinking water safe levels for an influent volume equal to over 160 bed volumes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The use of acidified milk for feeding infants has a long, interesting history that appears to have developed from the use of buttermilk in Holland as early as the late 19th century for feeding infants with diarrhea. Physicians in the early 20th century assumed that the observed benefits were from buttermilk's acidity leading to the practice of acidifying infant formula. The historical and physiological perspective on the use of acidified infant formula is now especially relevant with the emergence of an acidified liquid human milk fortifier for preterm infants. Here, we review that history, with a deeper dive into the contemporary research on the use of acidified human milk fortifiers, the consequences for preterm infants, and the underlying physiological mechanisms. KEY POINTS: · In the late 19th and early 20th century acidified feedings were in common use for sick infants.. · By the mid-20th century, acidified feedings tested in preterm infants resulted in acidic physiology and poor growth.. · The current practice of acidifying feedings in preterm infants has been associated with metabolic acidosis, poor tolerance, and delayed growth.., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.B.R. and G.E.B. are employees of Abbott Nutrition, Abbott Laboratories.M.L.M. is a paid consultant and national speaker for Abbott Nutrition., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The increasing demand and implementation of pharmaceutics poses severe risk to different aquatic species as detectable contaminant in almost every surface water worldwide. Diclofenac (DCF) as one of the most common used analgesics was investigated as contaminant to be removed by adsorption onto nanoporous poly(melamine-co-formaldehyde) (PMF) particles featuring a very high amount of nitrogen functionalities. To achieve a high specific surface area (up to 416 m 2 /g) and a tunable pore system by hard templating, four different SiO 2 nanoparticles were used as template. Differences in the pore formation and achieved pore structure were elucidated. For the first time, the adsorption of DCF onto PMF was tested. In batch adsorption experiments, impactful adsorption capacities as high as 76 μmol/g were achieved and complete removal at initial concentrations of 2 mg/L DCF. Differences in the connectivity and the micropore structure were decisive for uptake in low concentrations and the achieved adsorption capacity, respectively. As the presented PMF particles can be easily synthesized with the monomers formaldehyde and melamine combined with colloidal silica as sacrificial template and water as green solvent, this material presents a viable adsorbent for the removal of DCF at a larger scale. Our study further indicates a high potential for the removal of other pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the surgical rehabilitation of cleft lip and/or palate by the Brazilian public health system., Methods: Retrospective, analytical and comparative ecological study, with information on hospital procedures performed on individuals with cleft lip and/or palate in Centers authorized by the Brazilian public health system, between the years 2008 and 2020. The information was collected in databases Ministry of Health data., Results: Between 2008 and 2020, there was an increase of 8 (36.4%) qualified Centers in Brazil, currently having 30 Centers in 100% of the geographic regions. The surgical procedures performed totaled 68,716; with multiple surgeries being the most frequent. Complete cleft lip and palate was the most frequent type in hospital admissions. The public financial resources invested in the surgical rehabilitation of cleft lip and palate in the qualified Lip and Palate Malformation Treatment Centers were US$ 39,693 million, making an average value per procedure of US$ 577.64., Conclusions: In Brazil, public health system performed and financed, over the years 2008 and 2020, an important volume of surgical procedures for cleft lip and/or palate, which presented a polarization in the Southeast region but with a slight tendency expansion to other regions of the country. The most performed surgical procedures were multiple surgeries and mostly for individuals with cleft lip and palate. The amounts paid showed a heretogeneous distribution in the national territory., Level of Evidence: Level 5: Report containing program evaluation data., (Copyright © 2022 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) is a disease with a high rate of transmission. Serological tests are important to perform surveys and to determine the immunological status of the population. Based on this, we evaluated three enzyme-linked immunoassays (ELISAs) using different antigens from SARS-CoV-2 in a cohort of 161 patients. The performance of the ELISA developed for immunoglobulin G (IgG) measurement against SARS-CoV-2 was evaluated based on sensitivity, specificity, and accuracy. We found specificities of 0.98, 0.98, and 0.99 and sensitivities of 0.99, 0.91, and 0.87 for the nucleocapsid (N) protein, spike protein, and receptor binding domain (RBD) fraction, respectively. The accuracy assessment indicated the N protein (accuracy = 0.98) as the antigen most likely to give a correct diagnosis. Overall, the antibody responses were present for all three proteins in subjects with confirmed SARS-CoV-2 infections, showing a similar pattern of antibody production for different antigens. In summary, these highly sensitive and specific ELISAs, with a more competitive price, appear to be a valid approach for the serodiagnosis of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2022 Cássio Meira et al.)

Quantifying digestive and fermentative processes within the rumen environment has been the subject of decades of research; however, our existing research methodologies preclude time-sensitive and spatially explicit investigation of this system. To better understand the temporal and spatial dynamics of the rumen environment, real-time and in situ monitoring of various chemical and physical parameters in the rumen through implantable microsensor technologies is a practical solution. Moreover, such sensors could contribute to the next generation of precision livestock farming, provided sufficient wireless data networking and computing systems are incorporated. In this review, various microsensor technologies applicable to real-time metabolic monitoring for ruminants are introduced, including the detection of parameters for rumen metabolism, such as pH, temperature, histamine concentrations, and volatile fatty acid concentrations. The working mechanisms and requirements of the sensors are summarized with respect to the selected target parameters. Lastly, future challenges and perspectives of this research field are discussed., (© 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The intestinal epithelium comprises the body's largest surface exposed to viruses. Additionally, the gut epithelium hosts a large population of intraepithelial T lymphocytes, or IELs, although their role in resistance against viral infections remains elusive. By fate-mapping T cells recruited to the murine intestine, we observed an accumulation of newly recruited CD4 + T cells after infection with murine norovirus CR6 and adenovirus type-2 (AdV), but not reovirus. CR6- and AdV-recruited intraepithelial CD4 + T cells co-expressed Ly6A and chemokine receptor CCR9, exhibited T helper 1 and cytotoxic profiles, and conferred protection against AdV in vivo and in an organoid model in an IFN-γ-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4 + T cells prior to AdV infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A + CCR9 + CD4 + T cells against enteric adenovirus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This practice improvement project sought to determine the prevalence of psychiatric diagnoses among patients admitted to a community hospital's inpatient medical units and which diagnoses were serviced by the hospital's psychiatric consultation service., Method: Electronic medical record data on adult patients of five medical units admitted with a psychiatric condition between October 1, 2019, and December 31, 2019, were used. Psychiatric ICD-10 ( International Classification of Diseases, 10th Revision ) codes and diagnosis names extracted were categorized into seven major diagnostic groups. A total of 687 adult patients with 82 psychiatric ICD-10 codes were analyzed using descriptive statistics., Results: Substance-related and addictive disorders were the most prevalent psychiatric diagnoses. Ninety-six percent ( n = 658) of patients residing on medical floors with psychiatric disorders were hospitalized for a principal medical problem. Seventy-three cases received psychiatric consultations during their stay. Sixty percent ( n = 44) of those cases had psychiatric disorders from two or more diagnostic categories., Conclusions: Multidisciplinary, team-based health care delivery models that include a psychiatric nurse can provide an effective approach to treat patients in community hospitals with multiple psychiatric and medical comorbidities. Hospitals could take a significant role in providing substance use disorder treatment and equipping medical nurses with training to competently care for patients with psychiatric disorders on medical units. Further research into the prevalence and impact of patients with co-occurring and multiple psychiatric diagnoses in community hospitals is needed to implement effective health care delivery models and provide appropriate treatment options in the community.

This study aimed to evaluate the effects of short-term supplementation, with 2% Chlorella vulgaris ( C. vulgaris ) biomass and two 0.1% C. vulgaris extracts, on the health status (experiment one) and on the inflammatory response (experiment two) of gilthead seabream ( Sparus aurata ). The trial comprised four isoproteic (50% crude protein) and isolipidic (17% crude fat) diets. A fishmeal-based (FM), practical diet was used as a control (CTR), whereas three experimental diets based on CTR were further supplemented with a 2% inclusion of C. vulgaris biomass (Diet D1); 0.1% inclusion of C. vulgaris peptide-enriched extract (Diet D2) and finally a 0.1% inclusion of C. vulgaris insoluble fraction (Diet D3). Diets were randomly assigned to quadruplicate groups of 97 fish/tank (IBW: 33.4 ± 4.1 g), fed to satiation three times a day in a recirculation seawater system. In experiment one, seabream juveniles were fed for 2 weeks and sampled for tissues at 1 week and at the end of the feeding period. Afterwards, randomly selected fish from each group were subjected to an inflammatory insult (experiment two) by intraperitoneal injection of inactivated gram-negative bacteria, following 24 and 48 h fish were sampled for tissues. Blood was withdrawn for haematological procedures, whereas plasma and gut tissue were sampled for immune and oxidative stress parameters. The anterior gut was also collected for gene expression measurements. After 1 and 2 weeks of feeding, fish fed D2 showed higher circulating neutrophils than seabream fed CTR. In contrast, dietary treatments induced mild effects on the innate immune and antioxidant functions of gilthead seabream juveniles fed for 2 weeks. In the inflammatory response following the inflammatory insult, mild effects could be attributed to C. vulgaris supplementation either in biomass form or extract. However, the C. vulgaris soluble peptide-enriched extract seems to confer a protective, anti-stress effect in the gut at the molecular level, which should be further explored in future studies.

Importance: Half of the people who die by suicide make a health care visit within 1 month of their death. However, clinicians lack the tools to identify these patients., Objective: To predict suicide attempts within 1 and 6 months of presentation at an emergency department (ED) for psychiatric problems., Design, Setting, and Participants: This prognostic study assessed the 1-month and 6-month risk of suicide attempts among 1818 patients presenting to an ED between February 4, 2015, and March 13, 2017, with psychiatric problems. Data analysis was performed from May 1, 2020, to November 19, 2021., Main Outcomes and Measures: Suicide attempts 1 and 6 months after presentation to the ED were defined by combining data from electronic health records (EHRs) with patient 1-month (n = 1102) and 6-month (n = 1220) follow-up surveys. Ensemble machine learning was used to develop predictive models and a risk score for suicide., Results: A total of 1818 patients participated in this study (1016 men [55.9%]; median age, 33 years [IQR, 24-46 years]; 266 Hispanic patients [14.6%]; 1221 non-Hispanic White patients [67.2%], 142 non-Hispanic Black patients [7.8%], 64 non-Hispanic Asian patients [3.5%], and 125 non-Hispanic patients of other race and ethnicity [6.9%]). A total of 137 of 1102 patients (12.9%; weighted prevalence) attempted suicide within 1 month, and a total of 268 of 1220 patients (22.0%; weighted prevalence) attempted suicide within 6 months. Clinicians' assessment alone was little better than chance at predicting suicide attempts, with externally validated area under the receiver operating characteristic curve (AUC) of 0.67 for the 1-month model and 0.60 for the 6-month model. Prediction accuracy was slightly higher for models based on EHR data (1-month model: AUC, 0.71; 6 month model: AUC, 0.65) and was best using patient self-reports (1-month model: AUC, 0.76; 6-month model: AUC, 0.77), especially when patient self-reports were combined with EHR and/or clinician data (1-month model: AUC, 0.77; and 6 month model: AUC, 0.79). A model that used only 20 patient self-report questions and an EHR-based risk score performed similarly well (1-month model: AUC, 0.77; 6 month model: AUC, 0.78). In the best 1-month model, 30.7% (positive predicted value) of the patients classified as having highest risk (top 25% of the sample) made a suicide attempt within 1 month of their ED visit, accounting for 64.8% (sensitivity) of all 1-month attempts. In the best 6-month model, 46.0% (positive predicted value) of the patients classified at highest risk made a suicide attempt within 6 months of their ED visit, accounting for 50.2% (sensitivity) of all 6-month attempts., Conclusions and Relevance: This prognostic study suggests that the ability to identify patients at high risk of suicide attempt after an ED visit for psychiatric problems improved using a combination of patient self-reports and EHR data.

Background: There is little published data on how to prepare probiotic supplements for enteral delivery in the NICU. The objective of this study was to determine how a three-strain probiotic blend (Bb-02, TH-4® and BB-12®) would behave when mixed and held for 4 hours with saline water, sterile water, dextrose 5% in water (D5W), 24 kcal preterm formula, and human milk., Methods: A packet of a three-strain probiotic supplement was mixed with 3 mL of saline water, sterile water, D5W, 24 kcal preterm formula, and human milk (tested at 3 mL and 2 mL). Samples were stored at room temperature for 60 minutes then refrigerated for 180 minutes. Probiotic survival, using quantitative enumeration, and pH were monitored over 4 hours. Samples were passed through a 5 French (Fr) feeding tube at the end of the study to evaluate viscosity., Results: The largest variation in total cell count from 0-time was sterile water with a + 0.26 log(CFU)/mL change at 90 minutes and typical variation is considered±0.50 log units indicating no significant change between samples in 4 hours. Saline water had the lowest final pH at 4.88. All samples easily passed through a 5 Fr feeding tube., Conclusion: The study showed minimal change in cell counts across solutions for 4 hours of storage, indicating health care facilities may be able to prepare probiotic supplements with a variety of solutions in pharmacies or milk rooms. This allows greater flexibility for probiotic delivery to preterm infants.

Case Presentation: Arboviruses primarily consist of RNA, which favours greater genetic plasticity, with a higher frequency of mutations that allow the virus to adapt to different hosts. The initial symptomatology is nonspecific, in that the patient can present fever, myalgia, arthralgia, rash and headache. This makes a clinical diagnosis using laboratory tests difficult and time-consuming. In Brazil, the main arboviruses involved in epidemics belong to the family Flaviviridae . The patient in this case is from the municipality of São Bernardo do Campo, an area endemic for arboviruses. He presented symptoms of fever, myalgia and headache., Results: The multiplex assay for arboviruses detected genetic material from the dengue 2 and yellow fever viruses., Conclusion: This result confirms the importance of molecular tests showing high sensitivity and specificity that can assist clinical diagnosis, particularly in endemic areas during periods of outbreak for other arboviruses, like the epidemiological picture in Brazil in 2018, when significant co-circulation of dengue virus and yellow fever virus occurred. The presence of co-circulating arboviruses increases the chance of coinfection and demonstrates the importance of differential diagnosis., Competing Interests: The authors declare that there are no conflicts of interest., (© 2021 The Authors.)

This work aimed to evaluate the effects of dietary supplementation with β-glucans extracted from yeast ( Saccharomyces cerevisiae ) and microalga ( Phaeodactylum tricornutum ) on gene expression, oxidative stress biomarkers and plasma immune parameters in gilthead seabream ( Sparus aurata ) juveniles. A practical commercial diet was used as the control (CTRL), and three others based on CTRL were further supplemented with different β-glucan extracts. One was derived from S. cerevisiae (diet MG) and two different extracts of 21% and 37% P. tricornutum -derived β-glucans (defined as Phaeo21 and Phaeo37), to give a final 0.06% β-glucan dietary concentration. Quadruplicate groups of 95 gilthead seabream (initial body weight: 4.1 ± 0.1 g) were fed to satiation three times a day for 8 weeks in a pulse-feeding regimen, with experimental diets intercalated with the CTRL dietary treatment every 2 weeks. After 8 weeks of feeding, all groups showed equal growth performance and no changes were found in plasma innate immune status. Nonetheless, fish groups fed β-glucans supplemented diets showed an improved anti-oxidant status compared to those fed CTRL at both sampling points (i.e., 2 and 8 weeks). The intestinal gene expression analysis highlighted the immunomodulatory role of Phaeo37 diet after 8 weeks, inducing an immune tolerance effect in gilthead seabream intestine, and a general down-regulation of immune-related gene expression. In conclusion, the results suggest that the dietary pulse administration of a P. tricornutum 37% enriched-β-glucans extract might be used as a counter-measure in a context of gut inflammation, due to its immune-tolerant and anti-oxidative effects.

Due to the existence-threatening risk to aquatic life and entire ecosystems, the removal of oxyanions such as sulfate and phosphate from anthropogenic wastewaters, such as municipal effluents and acid mine drainage, is inevitable. Furthermore, phosphorus is an indispensable resource for worldwide plant fertilization, which cannot be replaced by any other substance. This raises phosphate to one of the most important mineral resources worldwide. Thus, efficient recovery of phosphate is essential for ecosystems and the economy. To face the harsh acidic conditions, such as for acid mine drainage, an adsorber material with a high chemical resistivity is beneficial. Poly(melamine- co -formaldehyde) (PMF) sustains these conditions whilst its very high amount of nitrogen functionalities (up to 53.7 wt.%) act as efficient adsorption sides. To increase adsorption capacities, PMF was synthesized in the form of mesoporous particles using a hard-templating approach yielding specific surface areas up to 409 m 2 /g. Different amounts of silica nanospheres were utilized as template and evaluated for the adsorption of sulfate and phosphate ions. The adsorption isotherms were validated by the Langmuir model. Due to their properties, the PMF particles possessed outperforming maximum adsorption capacities of 341 and 251 mg/g for phosphate and sulfate, respectively. Furthermore, selective adsorption of sulfate from mixed solutions of phosphate and sulfate was found for silica/PMF hybrid particles.

Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car). The aim of this work was to evaluate behavior parameters and pro-inflammatory factors (cytokines IL-1β, TNF-α and cathepsin-D levels), as well as the anti-inflammatory cytokine IL10 in striatum of knockout mice (Gcdh -/- ) and wild type (WT) mice submitted to a normal or a high Lys diet. The potential protective effects of L-car treatment on these parameters were also evaluated. Gcdh -/- mice showed behavioral changes, including lower motor activity (decreased number of crossings) and exploratory activity (reduced number of rearings). Also, Gcdh -/- mice had significantly higher concentrations of glutarylcarnitine (C5DC) in blood and cathepsin-D (CATD), interleukin IL-1β and tumor factor necrosis alpha (TNF-α) in striatum than WT mice. Noteworthy, L-car treatment prevented most behavioral alterations, normalized CATD levels and attenuated IL-1β levels in striatum of Gcdh -/- mice. Finally, IL-1β was positively correlated with CATD and C5DC levels and L-car was negatively correlated with CATD. Our results demonstrate behavioral changes and a pro-inflammatory status in striatum of the animal model of GA1 and, most importantly, L-car showed important protective effects on these alterations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities., Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage., Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R., Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83)., Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use., (©Ana Luísa Neves, Cristina Jácome, Tiago Taveira-Gomes, Ana Margarida Pereira, Rute Almeida, Rita Amaral, Magna Alves-Correia, Sandra Mendes, Cláudia Chaves-Loureiro, Margarida Valério, Cristina Lopes, Joana Carvalho, Ana Mendes, Carmelita Ribeiro, Sara Prates, José Alberto Ferreira, Maria Fernanda Teixeira, Joana Branco, Marta Santalha, Maria João Vasconcelos, Carlos Lozoya, Natacha Santos, Francisca Cardia, Ana Sofia Moreira, Luís Taborda-Barata, Cláudia Sofia Pinto, Rosário Ferreira, Pedro Morais Silva, Tania Monteiro Ferreira, Raquel Câmara, Rui Lobo, Diana Bordalo, Cristina Guimarães, Maria Espírito Santo, José Ferraz de Oliveira, Maria José Cálix Augusto, Ricardo Gomes, Inês Vieira, Sofia da Silva, Maria Marques, João Cardoso, Ana Morete, Margarida Aroso, Ana Margarida Cruz, Carlos Nunes, Rita Câmara, Natalina Rodrigues, Carmo Abreu, Ana Luísa Albuquerque, Claúdia Vieira, Carlos Santos, Rosália Páscoa, Carla Chaves-Loureiro, Adelaide Alves, Ângela Neves, José Varanda Marques, Bruno Reis, Manuel Ferreira-Magalhães, João Almeida Fonseca. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.09.2021.)

Today, there is a huge effort to develop cancer immunotherapeutics capable of combating cancer cells as well as the biological environment in which they can grow, adapt, and survive. For such treatments to benefit more patients, there is a great need to dissect the complex interplays between tumor cells and the host's immune system. Monitoring mechanisms of resistance to immunotherapeutics can delineate the evolution of key players capable of driving an efficacious antitumor immune response. In doing so, simultaneous and systematic interrogation of multiple biomarkers beyond single biomarker approaches needs to be undertaken. Zooming into cell-to-cell interactions using technological advancements with unprecedented cellular resolution such as single-cell spatial transcriptomics, advanced tissue histology approaches, and new molecular immune profiling tools promises to provide a unique level of molecular granularity of the tumor environment and may support better decision-making during drug development. This review will focus on how such technological tools are applied in clinical settings, to inform the underlying tumor-immune biology of patients and offer a deeper understanding of cancer immune responsiveness to immuno-oncology treatments., (©2021 American Association for Cancer Research.)

The modification of the biobased polymer chitosan is a broad and widely studied field. Herein, an insight into the hydrophobization of low-molecular-weight chitosan by substitution of amino functionalities with hexanoyl chloride is reported. Thereby, the influence of the pH of the reaction media was investigated. Further, methods for the determination of the degree of substitution based on 1 H-NMR, FTIR, and potentiometric titration were compared and discussed regarding their accuracy and precision. 1 H-NMR was the most accurate method, while FTIR and the potentiometric titration, though precise and reproducible, underlie the influence of complete protonation and solubility issues. Additionally, the impact of the pH variation during the synthesis on the properties of the samples was investigated by Cd 2+ sorption experiments. The adjusted pH values during the synthesis and, therefore, the obtained degrees of substitution possessed a strong impact on the adsorption properties of the final material.

Background: As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel's largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine., Methods: All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19-related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan-Meier estimator., Results: Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions., Conclusions: This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19-related outcomes, a finding consistent with that of the randomized trial., (Copyright © 2021 Massachusetts Medical Society.)

Analytic approaches to listening have favored something that is more akin to vision, consequently shaping the technique, aims and understandings of psychoanalysis in terms of the production of understandings and meanings. The aural aspects of listening have mostly been subsumed under this emphasis on the visual. Two models of analytic listening based in the visual are initially presented, listening-for, and listening-to. Illustrations show how listening in these approaches emphasize "seeing" (i.e. discovering or creating conscious understandings or meanings) pertaining to unconscious contents. A third mode of listening, listening-with, based in an aural approach, seeks neither understanding nor meaning thought to be hidden, in need of (co)construction, or needing to be made figurable. Listening-with does not seek to symbolize content either already there or understood to be present as unrepresented. Content is not what is listened for or to, understanding or meaning not the goal. Instead it is an abiding within a space not only of not-knowing but of not trying to know. Exploring the unlanguaged from this latter perspective will involve those portions of the analysand's mental life that are never transformed analytically into symbolized content, as well as experiences involving the patient's mental life that do not call for any such transformation or understanding. The first part of this paper will feature a theoretical discussion of these modes of listening and the second part will illustrate the conception of listening-with via three vignettes selected from the literature, each demonstrating different aspects of the position. These modes of listening are considered to not operate exclusively of each other, but are heuristically separated for the current investigation in order to highlight attention to listening to phenomena existing outside of symbolization or referentiality, phenomena that may never take a form.

Objectives: Several factors are commonly associated with the occurrence of post-operative infection after craniotomy. However, the risk factors associated with tumor surgery have been less intensively investigated. The aim of the present study was to analyze the risk factors for infection and categorize patients according to risk rate., Methods: In this study, we retrospectively evaluated 987 adult patients consecutively submitted to craniotomy for tumor resection. The primary outcome was the occurrence of infection within 30 days after surgery. The following independent variables were assessed: age, gender, surgery duration, length of hospital stay prior to surgery, reoperation, body mass index, serum albumin, hemoglobin, lactic dehydrogenase, smoking, diabetes, corticoid use, preoperative chemotherapy, previous irradiation, elective or urgent indication for surgery, supra or infratentorial lesion location, and tumor histology. We performed a recursive partitioning analysis to assess the relative importance of these variables in predicting infection., Results: The model returned a 3-level classification: 1. CSF-leakage (relative contribution 70%), 2. Emergency surgery indication (18%), and 3. Tumor histology (8%). Additionally, partitioning clustered together 3 risk groups: 1. CSF-leakage group (probability of infection 72.5%), 2. No CSF-leakage and urgent surgery (mean probability 18.1%); and 3. no CSF-leakage and no urgent surgery (3.4%). The misclassification rate was 4.5%, the overall specificity and sensitivity were 99.6% and 75.5%, respectively, and the area under the ROC-curve was 0.6908., Conclusion: Our analysis indicates that technical and treatment-related factors are significantly more relevant than patient- or disease-related factors in determining the risk of postoperative infection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci., Competing Interests: TK has received honoraria from Lilly for providing methodological consultation and from Novartis for presenting a lecture in Neuroepidemiology. He further has received an honorarium from The BMJ for editorial services. DC has received an honorarium from Amgen for a presentation on migraine genetics. 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 © 2021 Kossowsky, Schuler, Giulianini, Berde, Reis, Ridker, Buring, Kurth and Chasman.)

This work deals with two new molecule-based materials, namely Ni II -complexes of general formulae [Ni(L1) 2 ] (Ni1) and [Ni(L2) 2 ] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 2 1 /c, also the asymmetric unit comprises of one Ni II ion located on an inversion centre and one anionic ligand, which acts as a κ 2 N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC 50 values ranges of 3.70 - 41.37 μM and 1.06 - 14.91 μM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 μM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (K b values ~10 4  mol L - -1 ) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (K b values ⁓10 3  mol L -1 )., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Precision technologies for confinement animal agricultural systems have increased rapidly over the past decade, though precision technology solutions for pastured livestock remain limited. There are a number of reasons for this limited expansion of technologies for pastured animals, including networking availability and reliability, power requirements, and expense, among others. The objective of this work was to demonstrate a rapidly deployable long-range radio (LoRa) based, low-cost sensor suite that can be used to track location and activity of pastured livestock. The sensor is comprised of an inexpensive Arduino-compatible microprocessor, a generic MPU-9250 motion sensor which contains a 3-axis accelerometer, 3-axis magnetometer, and a 3-axis gyroscope, a generic GPS receiver, and a RFM95W generic LoRa radio. The microprocessor can be programmed flexibly using the open source Arduino IDE software to adjust the frequency of sampling, the data packet to send, and what conditions are needed to operate. The LoRa radio transmits to a Dragino LoRa gateway which can also be flexibly programmed through the Arduino IDE software to send data to local storage or, in cases where a web or cellular connection is available, to cloud storage. The sensor was powered using a USB cord connected to a 3,350 mAh lithium-ion battery pack. The Dragino gateway was programmed to upload data to the ThingSpeak IoT application programming interface for data storage, handling, and visualization. Evaluations showed minimal benefit associated with reducing sampling frequency as a strategy to preserve battery life. Packet loss ranged from 40% to 60%. In a 3 d evaluation on pastured sheep, the sensor suite was able to report GPS locations, inertial sensor readings, and temperature. Preliminary demonstrations of our system are satisfactory to detect animal location based on GPS data in real-time. This system has clear utility as a lower-cost strategy to deploy flexible, useful precision technologies for pasture-based livestock species., (The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the FAM20A gene. The syndrome is characterized by impaired amelogenesis of the hypoplastic type and nephrocalcinosis, presenting with presence of thin or absence of enamel, late dental eruption, intrapulpal calcifications, bilateral nephrocalcinosis, and normal plasma calcium level. The objective is to characterize ERS by systematically literature reviewing, highlighting the main findings of the syndrome to increase knowledge about this condition in the health professionals. The study is a systematic review of the scientific literature, whose research was developed in the PubMed database in March 2018. A total of 69 articles were found. Two authors analyzed their abstracts and selected, according to the language and main subject, 30 articles to write this study. A total of 69 patients were cited in the studies and their data were analysed. There was gender equivalence and the ages ranged from 1 to 64 years old. There is a clear hereditary relation of the syndrome, since there was consanguinity in 18 cases, indicating a percentage of 26.08% and family history in 30 cases (43.47%). Laboratory changes vary greatly from patient to patient and may even remain unchanged. The relationship between the syndrome and the mutation in the FAM20A gene can be proven from the data, since all patients with ERS screened by the mutation were positive. With the advancement of the ERS studies, some associations with the syndrome are suspected, such as the presence of gingival fibromatosis, hearing loss, and hypertrichosis. Thus, it is noticed that the syndrome does not show a predilection for gender or age and there is a strong hereditary character, marked by the consanguinity and family history of the patients. The association with the FAM20A gene is reinforced, since the mutation was identified in all patients analyzed., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nephrology.)

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages' activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

Objective: To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS)., Methods: A dual prospective and retrospective cohort study involving 102 pairs of mothers and fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS)., Results: Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed., Conclusion: Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones., (© 2020 John Wiley & Sons Ltd.)

Monitoring mercury concentration in the marine environment is pivotal due to the risks that mercury intake poses to the ecosystem and human health. It is therefore of interest to make reliable, comparative measurements over large geographic areas. Here, the utility of wide-ranging generalist seabirds as mercury biomonitors at an ocean basin scale was assessed, using the Cory's Shearwater as a model species. The mercury concentration in flight feathers moulted at distant non-breeding areas of geolocator-tracked birds was quantified, reflecting contamination in various geographic areas. Compound-specific isotope analysis of amino acids was used to obtain comparable trophic positionestimates controlled for baseline isoscape. Birds that remained resident in the Canary Current integrated less mercury into their feathers than those that migrated to either the Benguela or Agulhas currents. Residents also occupied a significantly lower trophic position during the non-breeding season than migrants, largely explaining the difference in mercury exposure. Both mercury concentration and trophic position were similar in individuals spending the non-breeding period in the Benguela and Agulhas currents. This paper highlights the importance of accurate trophic position calculation in order to understand mercury exposure in wide-ranging predators and for meaningful spatial comparisons., 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 © 2020 Elsevier B.V. All rights reserved.)

Exposure to high temperatures can lead to thermotolerance in fish, which is hypothesized to potentially improve post-release survival in species under restocking programs, like Atlantic sturgeon. The aim of this study was to determine whether Atlantic sturgeon juveniles exposed to a 4-week temperature treatment respond differently to a subsequent heat shock than juveniles exposed to heat shock for the first time (naive fish). Response to heat shock was assessed by mapping the liver transcriptome. In total, 838 unique contigs were differentially expressed between the trained and the control group (592 downregulated, 261 upregulated, and 15 down- or upregulated, depending on the condition), corresponding to genes involved in the response to heat, tissue damage, proteolysis, and metabolism. Temperature-trained fish showed 2-4-fold fewer dysregulated contigs than naive fish, indicating their ability to maintain and recover homeostasis faster. During heat shock, hspc1 was upregulated in both experimental groups, while hspa1 and dnaja4 were exclusively upregulated in the control. Overall, compensatory mechanisms were observed in addition to the heat shock response. Only two genes, fgg and apnl, were upregulated at nearly all timepoints in both groups. Peptidases were more strongly downregulated in control fish, which also showed a reduction in lipid metabolism during recovery. Keratins, pck1, gadd45ga, and gadd45gb were differentially expressed between trained and control fish, and due to their roles in tissue protection and ER stress reduction, they might be responsible for the maintenance of the transcriptional homeostasis observed in trained fish.

Introduction: Preterm births account for disproportionately high healthcare costs, in large part due to expenses related to length of stay in the hospital neonatal intensive care unit (NICU). It is common for preterm infants to receive human milk fortifier (HMF) while in the NICU. Liquid HMF is available in both acidified and non-acidified formulations. A recent randomized clinical trial found that acidified HMF is associated with an increased incidence of metabolic acidosis, which may contribute to increased costs and longer NICU length of stay., Objective: The present study is a secondary analysis of these data, seeking to determine whether additional factors contribute to metabolic acidosis, whether metabolic acidosis is associated with longer hospital length of stay, and whether these associations contribute to the burden of hospital costs., Methods: The study sample consisted of 152 infants who were hospitalized in US NICUs. Multiple logistic regression was used to model the NICU length of stay. Data from the 2012 Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) were used to calculate the average cost (charge) per day in a NICU. Costs (charges) were adjusted to $US, year 2018 values, using the health Consumer Price Index., Result: Results indicated that acidified HMF was a strong predictor of metabolic acidosis, more so than gestational age or birth weight. Furthermore, metabolic acidosis was associated with incremental NICU costs (charges) of $US19,002 ($US65,462) per infant and longer NICU LOS., Conclusion: Future studies should further investigate factors that contribute to NICU length of stay and associated costs of care., Trial Registration: ClinicalTrials.gov: NCT02307760.

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

This in vitro study evaluated the effect of the application and previous photoactivation of bonding adhesives in lithium disilicate ceramics. This was achieved by analyzing the bond strength of the cement-ceramic interface, nanohardness and elastic modulus of bonding adhesives and resin cements. The bonding adhesives used were Scotchbond Multi-Purpose (SBMP); Scotchbond Multi-Purpose light-cured (SBMP+LC); Single Bond 2 (SB2); Single Bond 2 light-cured (SB2+LC); Single Bond Universal (SBU) and Single Bond Universal light-cured (SBU+LC). After luting the ceramic in composite resin blocks, all specimens were subjected to 10,000 thermocycles. Sticks were obtained for the microtensile bonding strength test and the nanohardness and elastic modulus of the bonding adhesive and resin cements. Data were submitted to one-way ANOVA and Fishers tests (α =0.05). The results indicated that the bonding strength and mechanical properties were influenced by the interaction of the bonding adhesive and resin cement. For the mechanical properties analyzed, no statistically significant differences were observed between the groups. Single Bond Universal was the only system that was effective with or without previous light activation. For the other adhesive systems, Scotchbond Multi- Purpose and Single Bond 2, the previous light activation was necessary to optimize the bonding strength of the adhesive interface., (Copyright© 2019 Dennis Barber Ltd.)

Purpose: To evaluate the microtensile bond strength of dentine/self-adhesive resin cement interface after several treatments on a dentine surface., Materials and Methods: Twenty-eight human molars were selected and divided into four groups: no treatment (control (C)); 2% chlorhexidine digluconate (CHX); 25% polyacrylic acid (PA); and 23 ppm dispersive solution of silver nanoparticle (SN). Prepolymerised TPH resin composite (Dentsply) blocks were luted on the dentine surface using RelyX U200 self-adhesive resin cement (3M ESPE). Microtensile bond strength was measured (MPa) in a universal testing machine 24 h and 6 months after the bonding process. The fractured specimens were examined in an optical microscope and classified according to the fracture pattern. A representative sample of each group was observed by scanning electronic microscope. Data were submitted to analysis of variance (ANOVA) and Tukey's test to compare the mean among the groups (p <0.05)., Results: The highest microtensile bond strength values after 24 h were found for the PA group (13.34 ± 6.36 MPa), with no statistically significant difference for the C group (9.76 ± 3.11 Mpa). After 6 months, the highest microtensile bond strength values were found for the C group (9.09 ± 3.27 Mpa), with statistically significant difference only for the CHX group (2.94 ± 1.66 MPa). There was statistically significant difference only for the PA group when comparing the periods studied. Regardless of the surface treatment applied, there were more adhesive failures in both periods of time., Conclusion: Dentinal pretreatment with PA, as well as use of SN before the bonding procedure of self-adhesive resin cement to dentine, may be alternative bonding protocols.