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Competing Interests: The authors report no conflicts of interest.

Environmental variation often induces plastic responses in organisms that can trigger changes in subsequent generations through non-genetic inheritance mechanisms. Such transgenerational plasticity thus consists of environmentally induced non-random phenotypic modifications that are transmitted through generations. Transgenerational effects may vary according to the sex of the organism experiencing the environmental perturbation, the sex of their descendants or both, but whether they are affected by past sexual selection is unknown. Here, we use experimental evolution on an insect model system to conduct a first test of the involvement of sexual selection history in shaping transgenerational plasticity in the face of rapid environmental change (exposure to pesticide). We manipulated evolutionary history in terms of the intensity of sexual selection for over 80 generations before exposing individuals to the toxicant. We found that sexual selection history constrained adaptation under rapid environmental change. We also detected inter- and transgenerational effects of pesticide exposure in the form of increased fitness and longevity. These cross-generational influences of toxicants were sex dependent (they affected only male descendants), and intergenerational, but not transgenerational, plasticity was modulated by sexual selection history. Our results highlight the complexity of intra-, inter- and transgenerational influences of past selection and environmental stress on phenotypic expression.

Infrared thermography is gaining relevance in breast cancer assessment. For this purpose, breast segmentation in thermograms is an important task for performing automatic image analysis and detecting possible temperature changes that indicate the presence of malignancy. However, it is not a simple task since the breast limit borders, especially the top borders, often have low contrast, making it difficult to isolate the breast area. Several algorithms have been proposed for breast segmentation, but these highly depend on the contrast at the lower breast borders and on filtering algorithms to remove false edges. This work focuses on taking advantage of the distinctive inframammary shape to simplify the definition of the lower breast border, regardless of the contrast level, which indeed also provides a strong anatomical reference to support the definition of the poorly marked upper boundary of the breasts, which has been one of the major challenges in the literature. In order to demonstrate viability of the proposed technique for an automatic breast segmentation, we applied it to a database with 180 thermograms and compared their results with those reported by others in the literature. We found that our approach achieved a high performance, in terms of Intersection over Union of 0.934, even higher than that reported by artificial intelligence algorithms. The performance is invariant to breast sizes and thermal contrast of the images., (© 2024 John Wiley & Sons Ltd.)

Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN + long-term repopulating HSCs (LT-HSCs; CD150 + CD48 - LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN - LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN + LT-HSCs were more quiescent compared to EMCN - LT-HSCs. Emcn -/- and Emcn +/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn -/- LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn -/- or Emcn +/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: Gonzalez F, None.

Conventional serum markers often fail to accurately detect cholestasis accompanying many liver diseases. Although elevation in serum bile acid (BA) levels sensitively reflects impaired hepatobiliary function, other factors altering BA pool size and enterohepatic circulation can affect these levels. To develop fluorescent probes for extracorporeal noninvasive hepatobiliary function assessment by real-time monitoring methods, 1,3-dipolar cycloaddition reactions were used to conjugate near-infrared (NIR) fluorochromes with azide-functionalized BA derivatives (BAD). The resulting compounds (NIRBADs) were chromatographically (FC and PTLC) purified (>95%) and characterized by fluorimetry, 1 H NMR, and HRMS using ESI ionization coupled to quadrupole TOF mass analysis. Transport studies using CHO cells stably expressing the BA carrier NTCP were performed by flow cytometry. Extracorporeal fluorescence was detected in anesthetized rats by high-resolution imaging analysis. Three NIRBADs were synthesized by conjugating alkynocyanine 718 with cholic acid (CA) at the COOH group via an ester (NIRBAD-1) or amide (NIRBAD-3) spacer, or at the 3α-position by a triazole link (NIRBAD-2). NIRBADs were efficiently taken up by cells expressing NTCP, which was inhibited by taurocholic acid (TCA). Following i.v. administration of NIRBAD-3 to rats, liver uptake and consequent release of NIR fluorescence could be extracorporeally monitored. This transient organ-specific handling contrasted with the absence of release to the intestine of alkynocyanine 718 and the lack of hepatotropism observed with other probes, such as indocyanine green. NIRBAD-3 administration did not alter serum biomarkers of hepatic and renal toxicity. NIRBADs can serve as probes to evaluate hepatobiliary function by noninvasive extracorporeal methods.

The vast majority of ingested foreign bodies (FB) can pass through the digestive tract without major incidences. In some cases, they accumulate in large amounts in the stomach. They can also perforate the gastrointestinal wall and migrate to extraluminal sites, remaining quiescent for many years. We report a case of a psychiatric patient with more than 100 ingested FB in the stomach., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To identify how value is defined in studies that focus on the value of molecular testing in cancer and the extent to which broadening the conceptualisation of value in healthcare has been applied in the molecular testing literature., Methods: A scoping review was undertaken using Joanna Briggs Institute (JBI) guidance. Medline, Embase, EconLit and Cochrane Library were searched in August 2023. Articles were eligible if they reported costs relative to outcomes, novel costs, or novel outcomes of molecular testing in cancer. Results were synthesised and qualitative content analysis was performed with deductive and inductive frameworks., Results: Ninety-one articles were included in the review. The majority (75/91) were conventional economic analyses (comparative economic evaluations and budget impact assessments) and undertaken from a healthcare system perspective (38/91). Clinical outcomes dominate the assessment of value (61/91), with quality-adjusted life-years (QALYs) the most common outcome measure (45/91). Other definitions of value were diverse (e.g. psychological impact, access to trials), inconsistent, and largely not in keeping with evolving guidance., Conclusions: Broader concepts of value were not commonly described in the molecular testing literature focusing on cancer. Conventional approaches to measuring the health costs and outcomes of molecular testing in cancer prevail with little focus on non-clinical elements of value. There are emerging reports of non-clinical outcomes of testing information, particularly psychological consequences. Intrinsic attributes of the testing process and preferences of those who receive testing information may determine the realised societal value of molecular testing and highlight challenges to implementing such a value framework., (© 2024. The Author(s).)

Water recycling and reuse are cornerstones of water management, which can be compromised by the presence of pollutants. Among these, pharmaceuticals can overcome standard water treatments and require sophisticated approaches to remove them. Sorption is an economically viable alternative limited by the need for sorbents with a sorption coefficient (Kd) higher than 500 L/kg. The cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in the presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU and high selectivity towards erythromycin (ERY) and ERY Kd higher than 4 × 10 3 L/kg, when tested against a cocktail of six drugs. Characterization of the polymers shows that both pDx1 and pDx5 have similar properties, fast sorption kinetics, and ERY Kd of 13.3 × 10 3 for pDx1 and 6.4 × 10 3 for pDx5 , representing 26.6 and 12.0 times the 500 L/kg threshold. The fact that new affinities and improvements in Kd can be achieved by cross-linking Dx in the presence of other molecules that promote pre-organization expands the applications of DVS cross-linked polysaccharides as sustainable, scalable, and environmentally friendly sorbents with a potential application in wastewater treatment plants (WTPs).

Objective: To evaluate the use of circular statistics to analyze retinal nerve fibre layer (RNFL) thickness in eyes with and without a prior history of optic neuritis (ON)., Design: Single-centre consecutive study., Participants: Twenty-two multiple sclerosis patients and 20 healthy control subjects., Methods: Data on 28 eyes with a history of ON of 22 multiple sclerosis patients and 40 eyes of 20 healthy control subjects collected in 2010 and 2015. RNFL thickness was measured separately in 12 sectors around the optic nerve head. We used circular statistics to calculate the mean weighted vector of RNFL thickness for each sector and eye in 2 measurements made 5 years apart (2010 and 2015). Comparisons of weighted mean vectors between groups were made using a paired Mardia-Watson-Wheeler test., Results: The directions of the mean weighted vectors for ON eyes were 45.8º in 2010 and 56.0º in 2015, whereas in control eyes the directions were 319.4º in 2010 and 188.9º in 2015. No significant differences were found between 2010 and 2015 in any of the 2 groups. However, significant differences were found between ON and control eyes in 2010 and 2015., Conclusions: This paper provides an example of how to use circular statistics in cases of directional data in ophthalmology and demonstrates that circular statistics are a suitable tool for this purpose., Competing Interests: Footnotes and Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Rare disease genomic testing is a complex process involving various resources. Accurate resource estimation is required for informed prioritization and reimbursement decisions. This study aims to analyze the costs and cost drivers of clinical genomic testing., Methods: Based on genomic sequencing workflows we microcosted limited virtual panel analysis on exome sequencing backbone, proband and trio exome, and genome testing for proband and trio analysis in 2023 Australian Dollars ($). Deterministic and probabilistic sensitivity analyses were undertaken., Results: Panel testing costs AUD $2373 ($733-$6166), and exome sequencing costs $2823 ($802-$7206) and $5670 ($2006-$11,539) for proband and trio analysis, respectively. Genome sequencing costs $4840 ($2153-$9890) and $11,589 ($5842-$16,562) for proband and trio analysis. The most expensive cost component of genomic testing was sequencing (36.9%-69.4% of total cost), with labor accounting for 27.1%-63.2% of total cost., Conclusion: We provide a comprehensive analysis of rare disease genomic testing costs, for a range of clinical testing types and contexts. This information will accurately inform economic evaluations of rare disease genomic testing and decision making on policy settings that assist with implementation, such as genomic testing reimbursement., Competing Interests: Conflict of Interest The authors have no direct pecuniary interests in the outputs of the study. Zornitza Stark, Sebastian Lunke, Stefanie Eggers, Simon Sadedin, Belinda Chong are employed by a genomics laboratory. The study is not supported by dedicated funding. The primary author is supported in his research activities by ongoing employment with the state government., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondrial genes play an essential role in energy metabolism. Variation in the mitochondrial DNA (mtDNA) sequence often exists within species, and this variation can have consequences for energy production and organismal life history. Yet, despite potential links between energy metabolism and the expression of animal behaviour, mtDNA variation has been largely neglected to date in studies investigating intraspecific behavioural diversity. We outline how mtDNA variation and interactions between mitochondrial and nuclear genotypes may contribute to the expression of individual-to-individual behavioural differences within populations, and why such effects may lead to sex differences in behaviour. We contend that integration of the mitochondrial genome into behavioural ecology research may be key to fully understanding the evolutionary genetics of animal behaviour., Competing Interests: Declaration of interests We have no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.

Whether sexual selection facilitates or hampers the ability to plastically respond to novel environments might depend on population structure, via its effects on sexual interactions and associated fitness payoffs. Using experimentally evolved lines of the seed beetle Callosobruchus maculatus, we tested whether individuals evolving under different sexual selection (monogamy vs. polygamy) and population spatial structure (metapopulation vs. undivided populations) treatments differed in their response across developmental thermal conditions (control, hot, or stressful) in a range of fitness and fitness-associated traits. We found that individuals from subdivided populations had lower lifetime reproductive success at hot temperatures, but only in lines evolving under relaxed sexual selection, revealing a complex interaction between sexual selection, population structure, and thermal environmental stress on fitness. We also found an effect of population structure on several traits, including fertility and adult emergence success, under exposure to high thermal conditions. Finally, we found a strong negative effect of hot and stressful temperatures on fitness and associated traits. Our results show that population structure can exacerbate the impact of a warming climate, potentially leading to declines in population viability, but that sexual selection can buffer the negative influence of population subdivision on adaptation to warm temperatures., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)

There is a growing trend in using saliva for SARS-CoV-2 detection with reasonable accuracy. We have studied the responses of IgA, IgG, and IgM in human saliva by directly comparing disease with control analyzing two-trace two-dimensional correlation spectra (2T2D-COS) employing Fourier transform infrared (FTIR) spectra. It explores the molecular-level variation between control and COVID-19 saliva samples. The advantage of 2T2D spectra is that it helps in discriminating remarkably subtle features between two simple pairs of spectra. It gives spectral information from highly overlapped bands associated with different systems. The clinical findings from 2T2D show the decrease of IgG and IgM salivary antibodies in the 50, 60, 65, and 75-years COVID-19 samples. Among the various COVID-19 populations studied the female 30-years group reveals defense mechanisms exhibited by IgM and IgA. Lipids and fatty acids decrease, resulting in lipid oxidation due to the SARS-CoV-2 in the samples studied. Study shows salivary thiocyanate plays defense against SARS-CoV-2 in the male population in 25 and 35 age groups. The receiver operation characteristics statistical method shows a sensitivity of 98% and a specificity of 94% for the samples studied. The measure of accuracy computed as F score and G score has a high value, supporting our study's validation. Thus, 2T2D-COS analysis can potentially monitor the progression of immunoglobulin's response function to COVID-19 with reasonable accuracy, which could help diagnose clinical trials. KEY MESSAGES: The molecular profile of salivary antibodies is well resolved and identified from 2T2D-COS FTIR spectra. The IgG antibody plays a significant role in the defense mechanism against SARS-CoV-2 in 25-40 years. 2T2D-COS reveals the absence of salivary thiocyanate in the 40-75 years COVID-19 population. The receiver operation characteristic (ROC) analysis validates our study with high sensitivity and specificity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The leaves of Psidium guajava L. are an agro-industrial by-product with an outstanding content of polyphenolic compounds; however, there are many factors which can affect the phytochemical profile when valuing this type of plant material, such as temperatures and extraction times involving in the extraction methods applied. In this context, this study analyzed the impact of different extraction methods (Soxhlet, maceration and ultrasound-assisted extraction) on the phytochemical profile (FTIR and UPLC-MS) and the antioxidant activity (ABTS, FRAP and Folin-Ciocalteu) of guava leaf extracts. A yield of phenolic compounds per gram of guava leaf was obtained within the range of 16 to 45 mg/g; on the other hand, the IC50 values determined with the ABTS assay ranged between 78 ± 4 to 152 ± 12 µg/mL. The methanolic extract obtained by Soxhlet was the one with the best reducing power, both in the FRAP assay and in the Folin-Ciocalteu assay. Finally, bioactive compounds such as quercetin, kaempferol and avicularin were identified in the guava leaf extract. It was concluded that the purification of polyphenolics compounds improves the antioxidant capacity, and that the extraction method greatly influences the phytochemical profile and activity of the extracts.

Aldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human ˃˃ rabbit ˃ pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Actinobacillus pleuropneumoniae (App) is a globally distributed Gram-negative bacterium that produces porcine pleuropneumonia. This highly contagious disease produces high morbidity and mortality in the swine industry. However, no effective vaccine exists to prevent it. The infection caused by App provokes characteristic lesions, such as edema, inflammation, hemorrhage, and necrosis, that involve different virulence factors. The colonization and invasion of host surfaces involved structures and proteins such as outer membrane vesicles (OMVs), pili, flagella, adhesins, outer membrane proteins (OMPs), also participates proteases, autotransporters, and lipoproteins. The recent findings on surface structures and proteins described in this review highlight them as potential immunogens for vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soto Perezchica, Guerrero Barrera, Avelar Gonzalez, Quezada Tristan and Macias Marin.)

Introduction: Genomic testing is a relatively new, disruptive and complex health technology with multiple clinical applications in rare diseases, cancer and infection control. Genomic testing is increasingly being implemented into clinical practice, following regulatory approval, funding and adoption in models of care, particularly in the area of rare disease diagnosis. A significant barrier to the adoption and implementation of genomic testing is funding. What remains unclear is what the cost of genomic testing is, what the underlying drivers of cost are and whether policy differences contribute to cost variance in different jurisdictions, such as the requirement to have staff with a medical license involved in testing. This costing study will be useful in future economic evaluations and health technology assessments to inform optimal levels of reimbursement and to support comprehensive and comparable assessment of healthcare resource utilisation in the delivery of genomic testing globally., Methods: A framework is presented that focuses on uncovering the process of genomic testing for any given laboratory, evaluating its utilisation and unit costs, and modelling the cost drivers and overall expenses associated with delivering genomic testing. The goal is to aid in refining and implementing policies regarding both the regulation and funding of genomic testing. A process-focused (activity-based) methodology is outlined, which encompasses resources, assesses individual cost components through a combination of bottom-up and top-down microcosting techniques and allows disaggregation of resource type and process step., Ethics and Dissemination: The outputs of the study will be reported at relevant regional genetics and health economics conferences, as well as submitted to a peer-reviewed journal focusing on genomics. Human research ethics committee approval is not required for this microcosting study. This study does not involve research on human subjects, and all data used in the analysis are either publicly available., Competing Interests: Competing interests: The authors have no direct pecuniary interests in the outputs of the study. ZS is employed by a genomics laboratory. The study is not supported by dedicated funding. The primary author is supported in his research activities by ongoing employment with the state government., (© 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.)

Background: Delirium is an underdiagnosed clinical syndrome typified by an acute alteration of mental state. It is an important problem in critical care and intensive care units (ICU) due to its high prevalence and its association with adverse outcomes. Delirium is a very distressing condition for patients, with a huge impact on their well-being. Diagnosis of delirium in the critical care setting is challenging. This is especially true for patients who are mechanically ventilated and are therefore unable to engage in a verbal interview. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a tool specifically designed to assess for delirium in the context of ICU patients, including those on mechanical ventilation. CAM-ICU can be administered by non-specialists to give a dichotomous delirium present/absent result., Objectives: To determine the diagnostic accuracy of the CAM-ICU for the diagnosis of delirium in adult patients in critical care units., Search Methods: We searched MEDLINE (Ovid SP, 1946 to 8 July 2022), Embase (Ovid SP, 1982 to 8 July 2022), Web of Science Core Collection (ISI Web of Knowledge, 1945 to 8 July 2022), PsycINFO (Ovid SP, 1806 to 8 July 2022), and LILACS (BIREME, 1982 to 8 July 2022). We checked the reference lists of included studies and other resources for additional potentially relevant studies. We also searched the Health Technology Assessment database, the Cochrane Library, Aggressive Research Intelligence Facility database, WHO ICTRP, ClinicalTrials.gov, and websites of scientific associations to access any annual meetings and abstracts of conference proceedings in the field., Selection Criteria: We included diagnostic studies enrolling adult ICU patients assessed using the CAM-ICU tool, regardless of language or publication status and reporting sufficient data on delirium diagnosis for the construction of 2 x 2 tables. Eligible studies evaluated the diagnostic performance of the CAM-ICU versus a clinical reference standard based on any iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria applied by a clinical expert., Data Collection and Analysis: Two review authors independently selected and collated study data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used two univariate fixed-effect or random-effects models to determine summary estimates of sensitivity and specificity. We performed sensitivity analyses that excluded studies considered to be at high risk of bias and high concerns in applicability, due mainly to the target population included (e.g. patients with traumatic brain injury). We also investigated potential sources of heterogeneity, assessing the effect of reference standard diagnosis and proportion of patients ventilated., Main Results: We included 25 studies (2817 participants). The mean age of participants ranged from 48 to 69 years; 15 of the studies included critical care units admitting mixed populations (e.g. medical, trauma, surgery patients). The percentage of patients receiving mechanical ventilation ranged from 11.8% to 100%. The prevalence of delirium in the studies included ranged from 12.5% to 83.9%. Presence of delirium was determined by the application of DSM-IV criteria in 13 out of 25 included studies. We assessed 13 studies as at low risk of bias and low applicability concerns for all QUADAS-2 domains. The most common issue of concern was flow and timing of the tests, followed by patient selection. Overall, we estimated a pooled sensitivity of 0.78 (95% confidence interval (CI) 0.72 to 0.83) and a pooled specificity of 0.95 (95% CI 0.92 to 0.97). Sensitivity analysis restricted to studies at low risk of bias and without any applicability concerns (n = 13 studies) gave similar summary accuracy indices (sensitivity 0.80 (95% CI 0.72 to 0.86), specificity 0.95 (95% CI 0.93 to 0.97)). Subgroup analyses based on diagnostic assessment found summary estimates of sensitivity and specificity for studies using DSM-IV of 0.79 (95% CI 0.72 to 0.85) and 0.94 (95% CI 0.90 to 0.96). For studies that used DSM-5 criteria, summary estimates of sensitivity and specificity were 0.75 (95% CI 0.67 to 0.82) and 0.98 (95% CI 0.95 to 0.99). DSM criteria had no significant effect on sensitivity (P = 0.421), but the specificity for detection of delirium was higher when DSM-5 criteria were used (P = 0.024). The relative specificity comparing DSM-5 versus DSM-IV criteria was 1.05 (95% CI 1.02 to 1.08). Summary estimates of sensitivity and specificity for studies recruiting < 100% of patients with mechanical ventilation were 0.81 (95% CI 0.75 to 0.85) and 0.95 (95% CI 0.91 to 0.98). For studies that exclusively recruited patients with mechanical ventilation, summary estimates of sensitivity and specificity were 0.91 (95% CI 0.76 to 0.97) and 0.98 (95% CI 0.92 to 0.99). Although there was a suggestion of differential performance of CAM-ICU in ventilated patients, the differences were not significant in sensitivity (P = 0.316) or in specificity (P = 0.493)., Authors' Conclusions: The CAM-ICU tool may have a role in the early identification of delirium, in adult patients hospitalized in intensive care units, including those on mechanical ventilation, when non-specialized, properly trained clinical personnel apply the CAM-ICU. The test is most useful for exclusion of delirium. The test may miss a proportion of patients with incident delirium, therefore in situations where detection of all delirium cases is desirable, it may be best to repeat the test or combine CAM-ICU with another assessment. Future studies should compare different screening tests proposed for bedside assessment of delirium, as this approach will reveal which tool yields superior accuracy. In addition, future studies should consider and report the flow and timing of the tests and clearly report key characteristics related to patient selection. Finally, future research should focus on the impact of CAM-ICU screening on patient outcomes., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Antimicrobial blue light (aBL) in the 400-470 nm wavelength range has been reported to kill multiple bacteria. This study assessed its potential for mitigating an important foodborne pathogen, Listeria monocytogenes (Lm), focusing on surface decontamination. Three wavelengths were tested, with gallic acid as a photosensitizing agent (Ps), against dried cells obtained from bacterial suspensions, and biofilms on stainless-steel (SS) coupons. Following aBL exposure, standard microbiological analysis of inoculated coupons was conducted to measure viability. Statistical analysis of variance was performed. Confocal laser scanning microscopy was used to observe the biofilm structures. Within 16 h of exposure at 405 nm, viable Lm dried cells and biofilms were reduced by approx. 3 log CFU/cm 2 with doses of 2,672 J/cm 2 . Application of Ps resulted in an additional 1 log CFU/cm 2 at 668 J/cm 2 , but its effect was not consistent. The highest dose (960 J/cm 2 ) at 420 nm reduced viable counts on the biofilms by 1.9 log CFU/cm 2 . At 460 nm, after 800 J/cm 2 , biofilm counts were reduced by 1.6 log CFU/cm 2 . The effect of material composition on Lm viability was also investigated. Irradiation at 405 nm (668 J/cm 2 ) of cells dried on polystyrene resulted in one of the largest viability reductions (4.0 log CFU/cm 2 ), followed by high-density polyethylene (3.5 log CFU/cm 2 ). Increasing the dose to 4,008 J/cm 2 from 405 nm (24 h), improved its efficacy only on SS and polyvinyl chloride. Biofilm micrographs displayed a decrease in biofilm biomass due to the removal of biofilm portions from the surface and a shift from live to dead cells suggesting damage to biofilm cell membranes. These results suggest that aBL is a potential intervention to treat Lm contamination on typical material surfaces used in food production.IMPORTANCECurrent cleaning and sanitation programs are often not capable of controlling pathogen biofilms on equipment surfaces, which transmit the bacteria to ready-to-eat foods. The presence of native plant microbiota and organic matter can protect pathogenic bacteria by reducing the efficacy of sanitizers as well as promoting biofilm formation. Post-operation washing and sanitizing of produce contact surfaces might not be adequate in eliminating the presence of pathogens and commensal bacteria. The use of a dynamic and harmless light technology during downtime and close of operation could serve as a useful tool in preventing biofilm formation and persistence. Antimicrobial blue light (aBL) technology has been explored for hospital disinfection with very promising results, but its application to control foodborne pathogens remains relatively limited. The use of aBL could be a complementary strategy to inactivate surfaces in restaurant or supermarket deli settings., Competing Interests: The authors declare no conflict of interest.

Background: Atrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility., Methods: Right atrial appendage tissues were isolated from human patients with AF versus sinus rhythm controls. Western blots, coimmunoprecipitation, and phosphorylation studies were performed to examine how the PP1c (PP1 catalytic subunit)-PPP1R12C interaction causes MLC2a dephosphorylation. In vitro studies of pharmacological MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with electrophysiology studies., Results: In human patients with AF, PPP1R12C expression was increased 2-fold versus sinus rhythm controls ( P =2.0×10 -2 ; n=12 and 12 in each group) with >40% reduction in MLC2a phosphorylation ( P =1.4×10 -6 ; n=12 and 12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF ( P =2.9×10 -2 and 6.7×10 -3 , respectively; n=8 and 8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a and dephosphorylation of MLC2a. Mice treated with lentiviral PPP1R12C vector demonstrated a 150% increase in left atrial size versus controls ( P =5.0×10 -6 ; n=12, 8, and 12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in mice treated with lentiviral PPP1R12C vector was significantly higher than in controls ( P =1.8×10 -2 and 4.1×10 -2 , respectively; n=6, 6, and 5)., Conclusions: Patients with AF exhibit increased levels of PPP1R12C protein compared with controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF., Competing Interests: Disclosures None.

COVID-19 has affected the entire world due to the rapid spread of SARS-CoV-2, mainly through airborne particles from saliva, which, being easily obtained, help monitor the progression of the disease. Fourier transform infrared (FTIR) spectra combined with chemometric analysis could increase the diagnostic efficiency of the disease. However, two-dimensional correlation spectroscopy (2DCOS) is superior to conventional spectra as it helps to resolve the minute overlapped peaks. In this work, we aimed to use 2DCOS and receiver operating characteristic (ROC) analyses to compare the immune response in saliva associated with COVID-19, which could be important in biomedical diagnosis. FTIR spectra of human saliva samples from male (575) and female (366) patients ranging from 20 to 85 ± 2 years of age were used for the study. Age groups were segregated as G1 (20-40 ± 2 years), G2 (45-60 ± 2 years), and G3 (65-85 ± 2 years). The results of the 2DCOS analysis showed biomolecular changes in response to SARS-CoV-2. 2DCOS analyses of the male G1 + (1579,1644) and -(1531,1598) cross peaks evidenced changes such as amide I > IgG. Female G1 cross peaks -(1504,1645), (1504,1545) and -(1391,1645) resulted in amide I > IgG > IgM. The asynchronous spectra in 1300-900 cm-1 of the G2 male group showed that IgM is more important in diagnosing infections than IgA. Female G2 asynchronous spectra -(1027,1242) and + (1068,1176) showed that IgA > IgM is produced against SARS-CoV-2. The G3 male group evidenced antibody changes in IgG > IgM. The absence of IgM in the female G3 population diagnoses a specifically targeted immunoglobulin associated with sex. Moreover, ROC analysis showed sensitivity (85-89 % men; 81-88 % women) and specificity (90-93 % men; 78-92 % women) for the samples studied. The general classification performance (F1 score) of the studied samples is high for the male (88-91 %) and female (80-90 %) populations. This high PPV (positive predictive value) and NPV (negative predictive value) verify our segregation of COVID-19 positive and negative sample groups. Therefore, 2DCOS with ROC analysis using FTIR spectra have the potential for a non-invasive approach to monitoring COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP)., Method: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation., Results: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness., Significance: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The receptive field (RF) of a visual neuron is the region of the space that elicits neuronal responses. It can be mapped using different techniques that allow inferring its spatial and temporal properties. Raw RF maps (RFmaps) are usually noisy, making it difficult to obtain and study important features of the RF. A possible solution is to smooth them using P-splines. Yet, raw RFmaps are characterized by sharp transitions in both space and time. Their analysis thus asks for spatiotemporal adaptive P-spline models, where smoothness can be locally adapted to the data. However, the literature lacks proposals for adaptive P-splines in more than two dimensions. Furthermore, the extra flexibility afforded by adaptive P-spline models is obtained at the cost of a high computational burden, especially in a multidimensional setting. To fill these gaps, this work presents a novel anisotropic locally adaptive P-spline model in two (e.g., space) and three (space and time) dimensions. Estimation is based on the recently proposed SOP (Separation of Overlapping Precision matrices) method, which provides the speed we look for. Besides the spatiotemporal analysis of the neuronal activity data that motivated this work, the practical performance of the proposal is evaluated through simulations, and comparisons with alternative methods are reported., (© 2022 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Introduction: Graves' disease is an autoimmune disorder. Goiter and Graves' orbitopathy are frequently seen clinically. It would be helpful for the diagnosis, grading, prognosis, and treatment of this condition if it was possible to find serum biomarkers to establish a connection between the plasma levels of these compounds and orbital changes., Methods: A retrospective study was performed by revising the medical records of 44 patients with Graves' orbitopathy and 15 controls. The Osirix software (Pixmeo, Geneva, Switzerland) was used for manual orbital measurements. Plasma levels of Graves' orbitopathy substances were obtained in the analytical review of the patients., Results: A greater muscle volume was observed in patients with Graves' orbitopathy in relation to the control group (p < 0.001). The clinical activity score (CAS) was associated to total muscle mass (p = 0.013) and retrorbital fat (p = 0.048). Our results indicated a direct relationship between serum concentrations of anti-thyroid peroxidase antibodies and inferior rectus thickening (p = 0.036); however, we did not observe a positive correlation between other muscle volumes and serum concentrations of various thyroid-related substances., Conclusions: This study is the first that uses Osirix measurement software to manually assess orbital features in patients with Graves' orbitopathy. These measurements were compared to the outcomes of tests performed in a laboratory. Among several serum biomarkers, anti-thyroid peroxidase appears to be a reliable biomarker that correlates positively with inferior rectus muscle thickness in patients with thyroid eye disease. This may help to improve the management of this disease., (© 2023. The Author(s).)

(1) Background: Malignancies are an important cause of mortality after solid organ transplantation. The purpose of this study was to analyze the incidence of malignancies in patients receiving lung transplants (LT) and their influence on patients' survival. (2) Methods: Review of consecutive LT from 1994 to 2021. Patients with and without malignancies were compared by univariable and multivariable analyses. Survival was compared with Kaplan-Meier and Cox regression analysis. (3) Results: There were 731 LT malignancies developed in 91 patients (12.4%) with related mortality of 47% ( n = 43). Native lung cancer, digestive and hematological malignancies were associated with higher lethality. Malignancies were more frequent in males (81%; p = 0.005), transplanted for emphysema (55%; p = 0.003), with cyclosporine-based immunosuppression (58%; p < 0.001), and receiving single LT (65%; p = 0.011). Survival was worse in patients with malignancies (overall) and with native lung cancer. Risk factors for mortality were cyclosporine-based immunosuppression (OR 1.8; 95%CI: 1.3-2.4; p < 0.001) and de novo lung cancer (OR 2.6; 95%CI: 1.5-4.4; p < 0.001). (4) Conclusions: Malignancies are an important source of morbidity and mortality following lung transplantation that should not be neglected. Patients undergoing single LT for emphysema are especially at higher risk of mortality due to lung cancer in the native lung.

This work aimed to determine the ability of Listeria innocua (L.i.) to colonize eight materials found in food-processing and packaging settings and to evaluate the viability of the sessile cells. We also selected four commonly used phytochemicals (trans-cinnamaldehyde, eugenol, citronellol, and terpineol) to examine and compare their efficacies against L.i. on each surface. Biofilms were also deciphered in chamber slides using confocal laser scanning microscopy to learn more about how phytochemicals affect L.i. The materials tested were silicone rubber (Si), polyurethane (PU), polypropylene (PP), polytetrafluoroethylene (PTFE), stainless steel 316 L (SS), copper (Cu), polyethylene terephthalate (PET), and borosilicate glass (GL). L.i. colonized Si and SS abundantly, followed by PU, PP, Cu, PET, GL, and PTFE surfaces. The live/dead status ranged from 65/35% for Si to 20/80% for Cu, and the estimates of cells unable to grow on Cu were the highest, reaching even 43%. Cu was also characterized by the highest degree of hydrophobicity (ΔG TOT = -81.5 mJ/m 2 ). Eventually, it was less prone to attachment, as we could not recover L.i. after treatments with control or phytochemical solutions. The PTFE surface demonstrated the least total cell densities and fewer live cells (31%) as compared to Si (65%) or SS (nearly 60%). It also scored high in hydrophobicity degree (ΔG TOT = -68.9 mJ/m 2 ) and efficacy of phytochemical treatments (on average, biofilms were reduced by 2.1 log 10 CFU/cm 2 ). Thus, the hydrophobicity of surface materials plays a role in cell viability, biofilm formation, and then biofilm control and could be the prevailing parameter when designing preventive measures and interventions. As for phytochemical comparison, trans-cinnamaldehyde displayed greater efficacies, with the highest reductions seen on PET and Si (4.6 and 4.0 log 10 CFU/cm 2 ). The biofilms in chamber slides exposed to trans-cinnamaldehyde revealed the disrupted organization to a greater extent than other molecules. This may help establish better interventions via proper phytochemical selection for incorporation in environment-friendly disinfection approaches., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Water use has been increasing globally by 1% per year, and recycling and re-use are critical issues compromised by the presence of pollutants. In this context, the design of novel materials and/or procedures for the large scale-removal of pollutants must be economically and environmentally feasible in order to be considered as part of the solution by emerging economies. We demonstrate that the cross-linking of biodegradable polysaccharides such as starch, dextrin, or dextrin and β-cyclodextrin with divinyl sulfone is an innovative strategy for synthesizing insoluble and eco-friendly sorbent polymers, including pSt , pDx and pCD-Dx . The evaluation of these polymers' ability to remove ciprofloxacin (CIP), a prime example of antibiotic pollution, revealed that pSt , with a Kd of 1469 L/kg and a removal rate higher than 92%, is a favorable material. Its sorption is pH-dependent and enhanced at a mildly alkaline pH, allowing for the desorption (i.e., cleaning) and reuse of pSt through an environmentally friendly treatment with 20 mM AcONa pH 4.6. The facts that pSt (i) shows a high affinity for CIP even at high NaCl concentrations, (ii) can be obtained from affordable starting materials, and (iii) is synthesized and regenerated through organic, solvent-free procedures make pSt a novel sustainable material for inland water and seawater remediation, especially in less developed countries, due to its simplicity and low cost.

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging., Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples., Main Results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations., Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities., Competing Interests: Emilio Gomez-Gonzalez reports financial support was provided by Spanish Ministry of Science and Innovation, Institute of Health ‘Carlos III’. Emilio Gomez-Gonzalez reports financial support was provided by Spanish Ministry of Science and Innovation and ERDF. Francisco Jose Garcia-Cozar reports financial support was provided by Spanish Ministry of Science and Innovation, Institute of Health ‘Carlos III’. Alejandro Barriga-Rivera reports financial support was provided by Spanish Ministry of Science and Innovation and ERDF. Olga Muñoz reports financial support was provided by Center of Excellence ‘Severo Ochoa’. Juan Carlos Gomez-Martin reports financial support was provided by Center of Excellence ‘Severo Ochoa’. Jose Luis Ramos reports financial support was provided by Center of Excellence ‘Severo Ochoa’. Olga Muñoz reports financial support was provided by Spanish Ministry of Science and Innovation (LEONIDAS Grant). Juan Carlos Gomez-Martin reports financial support was provided by Spanish Ministry of Science and Innovation (LEONIDAS Grant). Jose Luis Ramos reports financial support was provided by Spanish Ministry of Science and Innovation (LEONIDAS Grant). Emilio Gomez-Gonzalez has patent Apparatus and method for the optical detection of pathogens at a distance pending to Universidad de Sevilla and Andalusian Health Service. Alejandro Barriga-Rivera has patent Apparatus and method for the optical detection of pathogens at a distance pending to Universidad de Sevilla and Andalusian Health Service. Javier Marquez-Rivas has patent Apparatus and method for the optical detection of pathogens at a distance pending to Universidad de Sevilla and Andalusian Health Service. One coauthor serves as Handling Associate Editor for the Journal of Quantitative Spectroscopy & Radiative Transfer - Olga Muñoz, (© 2023 The Author(s).)

Recent approval of transdermal flunixin meglumine (FM) (Banamine ® ) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine the concentration of flunixin, 5OH flunixin, and eicosanoids (TXB2 and PGF2 alpha) using LC-MS/MS. The results indicated that both flunixin and 5OH flunixin were detectable in blood samples collected during TD. The elimination of the drug was slower following the TD route compared to PO and IV. TD administration significantly decreased TXB2 levels in non-stimulated serum from 1 to 96 h post-administration, while IV and PO resulted in TXB2 reduction for 1 to 8 h. A significant reduction in PGF2 alpha was observed in PO and IV 1 h after administration, while TD resulted in a gradual decline from 4 to 72 h. The study concluded that the off-label use of transdermal FM at 3.3 mg/kg could be effective in controlling inflammation in donkeys.

Purpose: Microcosting can provide valuable economic evidence to inform the translation of genomic sequencing to clinical practice. A systematic literature review was conducted to identify studies employing microcosting methods to estimate the cost of genomic sequencing to diagnose cancer and rare diseases., Methods: Four electronic databases, Medline, Embase, EconLit, and Cumulated Index to Nursing and Allied Health Literature were searched. Reference lists of identified studies were also searched. Studies were included if they had estimated the cost of genome sequencing or exome sequencing for cancer or rare disease diagnosis using microcosting methods., Results: Seven studies met the inclusion criteria. Cost estimates for genome sequencing and exome sequencing ranged between US$2094 and $9706 and US$716 and $4817 per patient, respectively. All studies disaggregated resource use and cost inputs into labor, equipment, and consumables, with consumables being the main cost component. Considerable differences in the level of detail used to report the steps and resources used in each of the sequencing steps limited study comparisons., Conclusion: Defining a standard microcosting methodology is challenging because of the heterogeneous nature of genomic sequencing. Reporting of detailed and complete sequencing procedures, inclusion of sensitivity analyses and clear justifications of resource use, and measurement of unit costs can improve comparability, transferability, and generalizability of study findings., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 μg, and 4, 3, and 2 weeks reaching 100 μg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.

The spotted wing Drosophila, Drosophila suzukii, has emerged within the past decade as an invasive species on a global scale, and is one of the most economically important pests in fruit and berry production in Europe and North America. Insect ecology, to a strong degree, depends on the chemosensory modalities of smell and taste. Extensive research on the sensory receptors of the olfactory and gustatory systems in Drosophila melanogaster provide an excellent frame of reference to better understand the fundamentals of the chemosensory systems of D. suzukii. This knowledge may enhance the development of semiochemicals for sustainable management of D. suzukii, which is urgently needed. Here, using a transcriptomic approach we report the chemosensory receptor expression profiles in D. suzukii female and male antennae, and for the first time, in larval heads including the dorsal organ that houses larval olfactory sensory neurons. In D. suzukii adults, we generally observed a lack of sexually dimorphic expression levels in male and female antennae. While there was generally conservation of antennal expression of odorant and ionotropic receptor orthologues for D. melanogaster and D. suzukii, gustatory receptors showed more distinct species-specific profiles. In larval head tissues, for all three receptor gene families, there was also a greater degree of species-specific gene expression patterns. Analysis of chemosensory receptor repertoires in the pest species, D. suzukii relative to those of the genetic model D. melanogaster enables comparative studies of the chemosensory, physiology, and ecology of D. suzukii., 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., (Published by Elsevier Inc.)

Background: Social distancing measures have been one of the core pillars of the strategy against COVID-19 in all the countries. This study aims at understanding what motivates behaviours and compliance with social distancing measures among students and workers from a Spanish public university., Methods: We carry out two logistics models considering two different dependent variables: not maintaining social relation with non-cohabiting people and not to leave home except for emergencies ( n  = 507, sample is formed by students and workers from the University of Cantabria in the North of Spain)., Results: Being very concerned about getting ill suggests higher risk of not maintaining social relation with non-cohabiting people. Getting older increase the probability of not leaving home except for emergencies as happens with those who are very concerned about getting ill. Young people often living with vulnerable older relatives may affect students' behaviour., Conclusions: Our findings suggest that compliance with social distancing measures depends on several factors related to age, the number or kind of cohabiting people and level of concern about getting ill. Policies should address all these factors through a multidisciplinary perspective., Competing Interests: The authors declare there are no competing interests., (©2023 Cantarero Prieto et al.)

Objectives: To report that the periorbital changes induced by prostaglandin analogue (PGA) eye drops are partially reversible after discontinuing treatment., Materials and Methods: Nine patients with prostaglandin-associated periorbitopathy seen in a referral oculoplastic practice were included in this study, eight with unilateral glaucoma and one with bilateral open-angle glaucoma. All of them had been treated with topical PGA for at least one year, before the treatment was discontinued for cosmetic reasons., Results: In all cases, there were evident periocular differences between the treated eye and the fellow eye, consisting mainly of deepening of the upper eyelid sulcus and eyelid fat pad reduction. One year after discontinuing the PGA eye drops, improvement of these features was observed., Conclusion: Clinicians and patients should be aware of the side effects of topical PGA therapy on periorbital tissues, and that these side effects can partially regress after discontinuation of the medication., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by Turkish Ophthalmological Association Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

The diamondback moth, Plutella xylostella (L.), is a worldwide pest of brassica crops, resistant to a large number of insecticides. As an alternative, the use of pheromone-baited traps has been proposed but farmers are yet to be convinced. In the present study, we aimed to validate the benefits of the use of pheromone-baited traps for monitoring and mass trapping in cabbage production in Central America as means of Integrated Pest Management (IPM) in comparison to calendarized insecticide sprays, which are the farmers' current practices (FCP). Mass trapping was established in nine selected plots of cabbage in Costa Rica and Nicaragua. Average captures of males/trap/night, plant damage and net profits of these IPM plots were compared to simultaneously evaluated or historically reported FCP plots. The results indicate that in Costa Rica, trap captures did not justify the application of insecticides and average net profits increased by more than 11% when the trapping methods were implemented. In Nicaragua, IPM plots were able to reduce insecticide applications to one third of those in FCP plots. These results confirm the economic and environmental benefits of pheromone-based management of DBM in Central America.

Mexico is one of the largest guava producers in the world, so it has access to a huge amount of waste and byproducts obtained after the industrial processing of the fruit. This review discusses the potential recovery of this residue for its application as an antimicrobial agent, considering the phytochemical composition, the bioactivity reported in-vivo and in-vitro , and the toxicology of the plant. Nowadays there is a growing demand for more natural and safer products, so the use of guava extracts is an interesting initiative, especially due to its availability in the country, its wide variety of traditional uses, and its phytochemical profile. This review highlights the importance and potential antimicrobial use of this plant in today's world., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gutierrez-Montiel, Guerrero-Barrera, Chávez-Vela, Avelar-Gonzalez and Ornelas-García.)

Various immunopathological events characterize the systemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Moreover, it has been reported that coronavirus disease 2019 (COVID-19) vaccination and infection by SARS-CoV-2 induce humoral immunity mediated by B-cell-derived antibodies and cellular immunity mediated by T cells and memory B cells. Immunoglobulins, cytokines, and chemokines play an important role in shaping immunity in response to infection and vaccination. Furthermore, different vaccines have been developed to prevent COVID-19. Therefore, this research aimed to analyze and compare Fourier-transform infrared (FTIR) spectra of vaccinated people with a positive (V-COVID-19 group) or negative (V-Healthy group) real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) test, evaluating the immunoglobulin and cytokine content as an immunological response through FTIR spectroscopy. Most individuals that integrated the V-Healthy group (88.1%) were asymptomatic; on the contrary, only 28% of the V-COVID-19 group was asymptomatic. Likewise, 68% of the V-COVID-19 group had at least one coexisting illness. Regarding the immunological response analyzed through FTIR spectroscopy, the V-COVID-19 group showed a greater immunoglobulins G, A, and M (IgG, IgA, and IgM) content, as well as the analyzed cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-ɑ), and interleukins 1β, 6, and 10 (IL-1β, IL-6, and IL-10). Therefore, we can state that it was possible to detect biochemical changes through FTIR spectroscopy associated with COVID-19 immune response in vaccinated people.

As a multitissue organ, the eye possesses unique anatomy and physiology, including differential expression of drug-metabolizing enzymes. Several hydrolytic enzymes that play a major role in drug metabolism and bioactivation of prodrugs have been detected in ocular tissues, but data on their quantitative expression is scarce. Also, many ophthalmic drugs are prone to hydrolysis. Metabolic characterization of individual ocular tissues is useful for the drug development process, and therefore, seven individual ocular tissues from human eyes were analyzed for the activity and expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC). Generic and selective human esterase substrates 4-nitrophenyl acetate (most esterases), D-luciferin methyl ester (CES1), fluorescein diacetate and procaine (CES2), and phenacetin (AADAC) were applied to determine the enzymes' specific activities. Enzyme kinetics and inhibition studies were performed with isoform-selective inhibitors digitonin (CES1) and verapamil and diltiazem (CES2). Enzyme contents were determined using quantitative targeted proteomics, and CES2 expression was confirmed by western blotting. The expression and activity of human CES1 among ocular tissues varied by >10-fold, with the highest levels found in the retina and iris-ciliary body. In contrast, human CES2 expression appeared lower and more similar between tissues, whereas AADAC could not be detected. Inhibition studies showed that hydrolysis of fluorescein diacetate is also catalyzed by enzymes other than CES2. This study provides, for the first time, quantitative information on the tissue-dependent expression of human ocular esterases, which can be useful for the development of ocular drugs, prodrugs, and in pharmacokinetic modeling of the eye. SIGNIFICANCE STATEMENT: Novel and comprehensive data on the protein expression and activities of carboxylesterases from individual human eye tissues are generated. In combination with previous reports on preclinical species, this study will improve the understanding of interspecies differences in ocular drug metabolism and aid the development of ocular pharmacokinetics models., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: The aim of this study was to determine whether the inclusion of older patients undergoing elective colorectal cancer resection in the Enhanced Recovery After Surgery (ERAS ® ) programme could improve clinical outcomes during hospital admission., Methods: A before-and-after study in ≥70-year-old patients electively admitted for colorectal cancer resection was designed. In total, 213 patients were included in the ERAS ® group, and 158 were included in the control group., Results: The average age was 77.9 years old (SD 5.31) and 57.14% of them were men, with a Charlson Index score of 3.42 (SD 3.32). The ERAS ® group presented a lower transfusion rate of 42 (19.7%), compared to 75 (47.5%) in the control group ( p < 0.001). The crude odds ratio (OR) for transfusion was 0.27 (95% CI 0.17-0.43; p < 0.001), and the adjusted odds ratio was 0.26 (95% CI 0.14-0.48; p < 0.001). The ERAS ® group had a lower percentage of patients with moderate-severe malnutrition on admission, at 23.4% (37 patients) against 36.2% in the control group (42 patients) ( p = 0.023), with an OR of 0.47 (95% CI 0.29-0.75; p < 0.002) and an adjusted OR of 0.48 (95% CI 0.29-0.78; p = 0.003). The number of patients who required admission to the intensive care unit (ICU) was also markedly lower: 54 from the ERAS ® group (25.4%) versus 71 from the control group (44.9%) ( p < 0.001)., Conclusions: The inclusion of ≥70-year-old adults in the ERAS ® programme resulted in a decrease in transfusions, number of erythrocyte concentrates transfused, and number of ICU admissions, along with improved nutritional status.

Background: Obstructive failure of implanted shunts is the most common complication in the treatment of hydrocephalus. Biological material and debris accumulate in the inner walls of the valve and catheters block the normal flow of the drained cerebrospinal fluid causing severe symptoms with high morbidity and mortality. Unfortunately, at present, there is no effective preventive protocol or cleaning procedure available., Objective: To assess whether externally applied, focused ultrasound beams can be used to resuspend deposits accumulated in brain shunts safely., Methods: A computational model of an implanted brain shunt was implemented to test the initial design parameters of a system comprising several ultrasound transducers. Under laboratory conditions, configurations with 3 and 4 transducers were arranged in a triangle and square pattern with their radiation axis directed towards a target model of the device, 2 catheters and a brain shunt filled with water and deposited graphite powder. The ultrasound beams were then concentrated on the device across a head model., Results: The computational model revealed that by using only 3 transducers, the acoustic field intensity on the valve was approximately twice that on the brain surface suggesting that acoustic cavitation could be selectively achieved. Resuspension of graphite deposits inside the catheters and the valve were then physically demonstrated and video-recorded with no temperature increase., Conclusion: The technology presented here has the potential to be used routinely as a noninvasive, preventive cleaning procedure to reduce the likelihood of obstruction-related events in patients with hydrocephalus treated with an implanted shunt., (Copyright © The Author(s) 2022. Published by Wolters Kluwer Health, Inc. on behalf of Congress of Neurological Surgeons.)

Background: As AF-associated morbidity and mortality are increasing, there is an acute need for improved surveillance and prevention strategies to reduce the impact of AF and related strokes. Specific echocardiographic parameters that can best predict future onset of AF within 3 months are lacking., Methods: Twenty patients with AF, as identified by presence of ICD-9 diagnosis code, were compared with a control group of twenty age- and sex-matched patients selected from the same clinic population but without a diagnosis of AF. Transthoracic echocardiograms (TTE) obtained within 90 days prior to first documented AF episode (study group) or obtained closest to first clinic visit (control) were selected for review., Results: Baseline characteristics, including age, BMI, presence of hypertension, hyperlipidemia, diabetes, and heart failure were comparable. Increased left atrial (LA) size (end systolic major axis in 2-chamber view: AF 4.62±0.03 vs control 3.79±0.21, P =0.03), increased mitral inflow (E/A ratio: AF 1.35±0.15 vs control 1.06±0.07, P =0.04), and reduced LA global longitudinal strain (AF -2.69±0.26 vs control - 3.59±0.31, P =0.04) were most closely associated with AF compared with the control group. Multivariate logistic regression was used to develop predictive models for AF onset. A combination of imaging and traditional clinical risk factors was the best AF prediction model with AUC of 0.94, which greatly exceeds the current best predictors published. From these parameters, we developed the SMASH2 scoring system for 90- day AF risk estimation., Conclusions: Risk factors for AF and early features of atrial cardiomyopathy including male sex, hypertension, LA enlargement, reduced mitral inflow, and reduced LA strain are powerful predictors of AF onset within 90 days, and may be used to prognosticate future AF risk., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The potential transmission of SARS-CoV-2 via food has been controversial since the beginning of the COVID-19 pandemic. To investigate these concerns, reliable detection methods and data on virus die-off rates in various foods are needed. Here, an FDA-standard method for the detection of enteric viruses' RNA from soft fruits was modified for the recovery of infectious SARS-CoV-2. Then, the survival of SARS-CoV-2 on berries was investigated as well as the effectiveness of washing virus-contaminated berries with water. The modified method did not significantly reduced log infectivity titers of recovered viruses, but berries did. The detection limit of the method for infectious SARS-CoV-2 was ∼2.97 log TCID50/g of berries. On SARS-CoV-2-inoculated berries that were stored at 4 °C for 7 days, significant reductions in SARS-CoV-2 infectivity were observed over time. In contrast, on frozen berries, infectious SARS-CoV-2 was recovered for 28 days without significant reductions. Washing SARS-CoV-2-inoculated berries with water removed >90% of infectious viruses within 10 min; however, infectious viruses were detected in wash water. Therefore, on fresh berries infectious viruses are markedly inactivated over time and can be largely removed by washing with water. However, the prolonged survival of SARS-CoV-2 on frozen berries suggests that the virus can potentially spread through frozen fruits., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chemotherapy-induced peripheral neuropathy is a common adverse effect of chemotherapeutic treatment and is associated with decreased quality of life. The aim of this study was to evaluate the validity and reliability of the neurotoxicity subscale of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) for the Chilean population., Methods: A cross-sectional study in which 101 participants with haematologic, colorectal, breast, gastric, gynaecological, and other types of cancer completed the FACT/GOG-Ntx. Content validity ( n = 14 health professionals evaluated the subscale in four categories: test-retest reliability ( n = 20 patients), dimensionality, internal consistency, and concurrent validity and discriminant validity. In all analyses, p < 0.05 was considered significant., Results: There was an agreement among the evaluators for all categories of the subscale (Kendall's coefficient, W = 0.4, p < 0.01) and moderate to high intrarater reliability (intraclass correlation coefficient = 0.7-0.9). Of the 11 original items that make up the subscale, none was eliminated. The factor analysis generated four factors that represented 72.2% of the total variance. Cronbach's α was 0.8 for the 11 items. Women showed greater compromise in emotional well-being and neurotoxicity symptoms compared with men, and age was directly correlated with the questions 'I have difficulty hearing' ( r = 0.2, p = 0.019) and 'I feel a noise or buzzing in my ears' ( r = 0.2, p = 0.03)., Conclusion: The Chilean version of the FACT/GOG-Ntx neurotoxicity subscale is a valid and reliable scale for evaluating neurotoxicity symptoms in adult cancer survivors in Latin America. The scales also adequately distinguish between sex-based well-being among the afflicted population., Competing Interests: The authors agree that there is no conflict of interest., (Copyright © 2022 Ivana Leao Ribeiro et al.)

Several reports have indicated that the thermal tolerance of Salmonella at low-water activity increases significantly, but information on the impact of diverse food matrices is still scarce. The goal of this research was to determine the kinetic parameters (decimal reduction time, D; time required for the first decimal reduction, δ) of thermal resistance of Salmonella in a previously cooked low water activity food. Commercial toasted oats cereal (TOC) was used as the food model, with or without sucrose (25%) addition. TOC samples were inoculated with 10 8 CFU/mL of a single strain of one of three Salmonella serovars (Agona, Tennessee, Typhimurium). TOC samples were ground and equilibrated to a w values of 0.11, 0.33 and 0.53, respectively. Ground TOC was heated at temperatures between 65 °C and 105 °C and viable counts were determined over time (depending on the temperature for up to 6 h). Death kinetic parameters were determined using linear and Weibull regression models. More than 70% of Weibull's adjusted regression coefficients (Radj2) and only 38% of the linear model's Radj2 had values greater than 0.8. For all serovars, both D and δ values increased consistently at a 0.11 a w compared to 0.33 and 0.53. At 0.33 a w , the δ values for Typhimurium, Tennessee and Agona were 0.55, 1.01 and 2.87, respectively, at 85 °C, but these values increased to 65, 105 and 64 min, respectively, at 0.11 a w . At 100 °C, δ values were 0.9, 5.5 and 2.3 min, respectively, at 0.11 a w . The addition of sucrose resulted in a consistent reduction of eight out of nine δ values determined at 0.11 a w at 85, 95 and 100 °C, but this trend was not consistent at 0.33 and 0.53 a w . The Z values (increase of temperature required to decrease δ-value one log) were determined with modified δ values for a fixed β (a fitting parameter that describes the shape of the curve), and ranged between 8.9 °C and 13.4 °C; they were not influenced by a w , strain or sugar content. These findings indicated that in TOC, high thermal tolerance was consistent among serovars and thermal tolerance was inversely dependent on a w .

Trans -sialidases (TS) are important constitutive macromolecules of the secretome present on the surface of Trypanosoma cruzi ( T. cruzi ) that play a central role as a virulence factor in Chagas disease. These enzymes have been related to infectivity, escape from immune surveillance and pathogenesis exhibited by this protozoan parasite. In this work, atomic force microscopy (AFM)-based single molecule-force spectroscopy is implemented as a suitable technique for the detection and location of functional TS on the surface of extracellular vesicles (EVs) released by tissue-culture cell-derived trypomastigotes (Ex-TcT). For that purpose, AFM cantilevers with functionalized tips bearing the anti-TS monoclonal antibody mAb 39 as a sense biomolecule are engineered using a covalent chemical ligation based on vinyl sulfonate click chemistry; a reliable, simple and efficient methodology for the molecular recognition of TS using the antibody-antigen interaction. Measurements of the breakdown forces between anti-TS mAb 39 antibodies and EVs performed to elucidate adhesion and forces involved in the recognition events demonstrate that EVs isolated from tissue-culture cell-derived trypomastigotes of T. cruzi are enriched in TS. Additionally, a mapping of the TS binding sites with submicrometer-scale resolution is provided. This work represents the first AFM-based molecular recognition study of Ex-TcT using an antibody-tethered AFM probe.