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Abstract Background Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. Methods Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60–75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. Discussion The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

Introduction A variety of peer support workers have been integrated in the mental health workforce in several countries. The effectiveness of this approach is still inconclusive. However, some data reveals promising results. Some projects have integrated peer support intervention in the treatment of psychosis. In fact, UK clinical guidelines for psychosis advise the inclusion of peer support within Early Intervention in Psychosis services. Objectives The current study aims to evaluate how peer support may assist the intervention in psychosis and highlight challenges ahead in this field. Methods Narrative review of the available scientific literature. Results Research suggests that consistent and frequent peer support enhances social support and boosts self-confidence and the overall quality of life for people going through psychosis. Individuals diagnosed with severe mental illnesses who receive peer support reportedly experience an increased sense of control, hopefulness, and empowerment, enabling them to initiate positive changes in their lives. People going through psychosis experience internalized stigma. Destigmatization of psychotic experiences is a central theme of intervention in psychosis. Participants viewed peer support as a valuable form of assistance that could offer advantages to both peers (service users) and peer support workers. Conclusions Peer support makes a strong contribution to destigmatising psychosis. The available date is promising and supports the effectiveness of peer support in such instances. As projects of peer support in psychosis continue to be implemented, further research should provide additional insight into the effectiveness and inherent challenges of this type of intervention. Disclosure of Interest None Declared

Introduction Irvin D. Yalom defines existential psychotherapy as a dynamic therapeutic approach that focuses on concerns rooted in existence with the four ultimate concerns being death, isolation, meaning in life, and freedom. Patients in advanced stages of cancer often experience elevated levels of psychological distress, encompassing conditions such as depression, anxiety, and a sense of spiritual hopelessness. Recently, interest in spiritual well-being has prompted a new wave of interventions that directly target this population, namely logotherapy and other existential interventions based on existential principles. Objectives In this review, the primary focus was to comprehend the current evidence on the application of existential psychotherapy for individuals coping with advanced cancer and give an overview of the therapy approaches used. Methods Narrative review of scientific literature using Pubmed search engine. Results Terao and Satoh identified nine types of existential psychotherapies which were investigated using randomized controlled trials for patients with advanced cancer or in terminal care: Meaning-Centered Group Psychotherapy (MCGP), Individual Meaning-Centered Psychotherapy (IMCP), Meaning-Making intervention (MMi), Meaning of Life Intervention, Managing Cancer and Living Meaningfully (CALM), Hope Intervention, Cognitive and Existential Intervention, Dignity Therapy, and Life-Review Interviews. All deal with the issues pointed by Yalom. Existential or spiritual well-being improvements were validated in MCGP, IMCP, Meaning of Life intervention, and Life-Review intervention. Conclusions Current evidence is still based on a very limited number of studies. Additional research is needed to delve into the impact of existential psychotherapy on individuals facing advanced cancer. Disclosure of Interest None Declared

Introduction Tourette’s syndrome (TS) is a disorder characterized by repetitive, involuntary movements, and vocalizations known as tics. While there are existing treatment options, there is a growing need for novel pharmacological approaches to manage the symptoms of TS effectively. This study delves into the emerging field of using cannabinoids as a potential treatment for Tourette’s syndrome. Objectives The primary objectives of this review are to examine the current evidence base for the use of cannabinoids in the treatment of Tourette’s syndrome, to assess the biological rationale supporting the use of cannabinoids in managing tic severity, to provide insights into the results of existing clinical trials involving cannabinoids and Tourette’s syndrome, and to draw conclusions regarding the potential efficacy and safety of cannabinoid-based treatments for TS. Methods Narrative review of the available scientific literature. Results There is a strong biological rationale for how cannabinoids could impact tic severity. The endocannabinoid system plays a crucial role in regulating various physiological processes, including motor control and neurotransmitter release. Activation of cannabinoid receptors in the brain may modulate these processes, potentially reducing tics. While limited, two small randomized, placebo-controlled trials of THC have been conducted in TS patients. These trials suggested potential benefits of cannabis-derived agents in reducing tic frequency and severity. Self-report and examiner rating scales demonstrated significant improvements in tic symptoms. The trials indicated that THC treatment did not result in significant adverse effects in TS patients. Conclusions The exploration of cannabinoids as a treatment option for Tourette’s syndrome is promising but requires further investigation. The biological mechanisms through which cannabinoids may affect tic severity in TS are sound, suggesting their potential as a therapeutic option. Existing trials with THC have shown encouraging results, demonstrating a reduction in tics without significant adverse effects. However, the limited number of trials warrants caution in drawing definitive conclusions. Despite the promising findings, the overall efficacy and safety of cannabinoid-based treatments remain largely unknown. Further trials are essential to address dosing, active ingredients, optimal administration, and potential long-term effects. Clinical use should be approached with caution. While early evidence is encouraging, additional rigorous studies are needed to establish the safety and efficacy of cannabinoid-based treatments for this disorder. Disclosure of Interest None Declared

Introduction Psychotherapy serves as the foundation of care for individuals with borderline personality disorder (BPD), with pharmacotherapy being regarded as a supplementary measure to be considered when necessary. In clinical practice, however, most of BPD patients receive medication. A major problem in the treatment of BPD is the lack of compliance derived from the pathological impulsivity of BPD patients. The use of long-acting antipsychotics (LAI) may be an option. Objectives This work aims to address the use of long-acting injectables in borderline personality disorder. Methods Non-systematic review of literature using the PubMed ® database, based on terms “Borderline Personality Disorder” and “Long-acting antipsychotics”. Only six articles were found. Results Several studies have shown promising results in the treatment of Borderline Personality Disorder (BPD) with long-acting injectable (LAI) antipsychotics. A six-month study using IM risperidone demonstrated significant improvement, while LAI Aripiprazole also exhibited positive outcomes in individuals with BPD and Substance Abuse. Additionally, Palomares et al. (2015) found that palmitate paliperidone LAI reduced impulsive-disruptive behaviors and enhanced overall functioning in BPD patients. Carmona et al. (2021) compared oral and LAI antipsychotics and concluded that LAIs may have a role to play in the management of BPD. Conclusions Treatment with LAIs may play an important role in clinical and functional improvement in BPD patients. Disclosure of Interest None Declared

Introduction The population ageing is a reality associated with an increase in prevalence of Dementia. The use of benzodiazepines is often postulated as a risk factor in these syndromes. Contrary to recommendations for its short-time use, long-term and chronic use are common, with an estimated 8,7% of elderly people in the US taking benzodiazepines. Objectives To clarify the most recent evidence on the use of benzodiazepines and the risk of developing dementia. Methods Non-systematic review of literature, using PubMed as database and filtering the results for meta-analysis. Results Four articles were included in this review. Zhong G et al. concluded that risk of dementia increased in consumers of benzodiazepines and it was associated with higher doses. In turn, AlDawasari A et al., when trying to clarify the use of different sedative-hypnotic drugs, found and increased risk with the consumption of benzodiazepines. After exclusion of articles with confounders and adjustment for protopathic bias, the risk was not maintained. Lucchetta RC et al. concluded that the risk exists but without inferring differences between doses or duration of action. Finally, Penninkilampi R e Eslick GD investigated this association, after controlling for the protopathic bias, concluding, contrary to AlDawasari et al., that the association benzodiazepines consumption and dementia do not result from this bias. Conclusions We cannot draw robust and concrete conclusions between benzodiazepines consumption and the pathogenesis of dementia because not only is the literature limited, but results are also heterogeneous. However, these prescriptions must be carried out cautiously, especially in the elderly, due to the known adverse effects associated with them. Disclosure of Interest None Declared

Background: Although incidence and mortality rates of colorectal cancer have progressively decreased during the past decades, early-onset rectal cancer (EORC;

In newborn ruminants, transfer of passive immunity is essential to obtain protection against pathogens. This study aimed to increase the permeability of the blood-milk barrier using intramammary lipopolysaccharides (LPS) in goats at parturition to modulate colostrum composition. Twenty multiparous Majorera dairy goats were randomly allocated in one of the two experimental groups. The LPS group (n = 10) received an intramammary administration (IA) of saline (2 mL) containing 50 µg of LPS from Escherichia coli (O55:B5) in each half udder at parturition. The control group (n = 10) received an IA of saline (2 mL). Rectal temperature (RT) was recorded, and a blood sample was collected at parturition (before IA). In addition, RT was measured, and blood and colostrum/milk samples were collected on day (d) 0.125 (3 hours), 0.5 (12 hours), 1, 2, 4, 7, 15 and 30 relative to the IA. Goat plasma immunoglobulin G (IgG) and M (IgM) and serum β-hydroxybutyrate, glucose, calcium, free fatty acids, lactate dehydrogenase and total protein concentrations were determined. Colostrum and milk yields as well as chemical composition, somatic cell count (SCC), IgG and IgM concentrations were measured. The MIXED procedure (SAS 9.4) was used, and the model included the IA, time, and the interaction between both fixed effects. Statistical significance was set as P

Place of residence (urban versus rural) is a contextual determinant of health that has received less attention in the food insecurity literature. The purpose of this study was to assess the urban–rural disparity in the prevalence of food insecurity and weight status among US children. Using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 with three age groups of children (2–5, 6–11, and 12–17 years old), the associations of weight status and child and household food security status by urban–rural residence were examined using Rao–Scott Chi-square tests. Statistical significance was set at p < 0.05. Children living in urban areas were significantly more likely to experience household food insecurity (29.15%) compared to their rural counterparts (19.10%), among those aged 6–11 years. The associations between children’s weight status and child and household food security status were significant for children living in urban areas overall and different age groups but not for children living in rural areas. These trends were more pronounced in older age groups. Given the link between food insecurity and higher obesity rates, particularly among urban children, this study highlights the importance of incorporating food security interventions into future obesity prevention programs.

Six novel phenylisoxazole semicarbazone derivatives 1–6 were synthesized by reaction of the corresponding phenylisoxazole-3/5-carbaldehyde derivatives with semicarbazide hydrochloride. The synthesized compounds were characterized by ESI-MS, FT-IR, and NMR (1H, 13C) spectroscopic techniques. The two-dimensional 1H-1H NOESY NMR (in acetone-d6) data revealed that compound 1 exists in the E isomeric form. The computational study of the energetic, structural, and electronic properties, carried out at B3LYP/6-311G++(d,p) level of theory, showed that the most stable conformer for the all synthesized compounds, in both gas and liquid (acetone and DMSO) phases, has a cisE geometrical configuration. This evidence found is in good agreement with the spectrometric results. The geometrical parameters, frontier molecular orbital (FMO), molecular electrostatic potential (MEP), Mulliken atomic charges, and natural bonding orbital (NBO) analysis were also performed at the same level of theory. Taking into account the relative enthalpies ΔH computed, we can establish for tautomeric structures of each of the compounds, the following stability order: I (cisE) > II (E′E) > III (cisE). The MEP descriptors indicate that the oxygen atom of the carbonyl group C=O is susceptible to electrophilic attack, while the hydrogen atoms of the amide and hydrazone fragments are sensitive to nucleophilic attack. The calculated HOMO-LUMO gap energies Eg indicate that 5 (in gas phase) and 6 (in liquid phase) are the most stable and less reactive compounds, while 1 is the less stable and the most reactive compound. From the NBO analysis, it becomes evident that the presence of the hydrazone fragment produces stabilizing effects due to hyperconjugative interactions.

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in the FNAP, and 88% were enrolled in school lunch programs. Children in urban areas were significantly more likely to report household food insecurity than those in rural areas (29.15% vs. 19.10%). The overall HEI-2015 score was 48.2. The associations between child/household FSS and FNAP participation as well as between child/household FSS and diet quality did not differ by urban/rural residence status, irrespective of the children’s age groups. There is a need for improvement in children’s diet quality, regardless of age or urban/rural residence. The findings suggest that improving children’s diets requires broader action as well as the prioritizing of children in urban areas experiencing food insecurity in future dietary interventions.

Cryptococcosis, caused by fungi of the genus Cryptococcus , manifests in a broad range of clinical presentations, including severe pneumonia and disease of the central nervous system (CNS) and other tissues (bone and skin). Immune deficiency or development of overexuberant inflammatory responses can result in increased susceptibility or host damage, respectively, during fungal encounters. Leukotrienes help regulate inflammatory responses against fungal infections. Nevertheless, studies showed that Cryptococcus exploits host 5-lipoxygenase (5-LO), an enzyme central to the metabolism of arachidonic acid into leukotrienes, to facilitate transmigration across the brain-blood barrier. To investigate the impact of host 5-LO on the development of protective host immune responses and mortality during cryptococcosis, wild-type (C57BL/6) and 5-lipoxygenase-deficient (5-LO -/- ) mice were given experimental pulmonary and systemic Cryptococcus sp., infections. Our results showed that 5-LO -/- mice exhibited reduced pathology and better disease outcomes (i.e., no mortality or signs associated with cryptococcal meningoencephalitis) following pulmonary infection with C. deneoformans, despite having detectable yeast in the brain tissues. In contrast, C57BL/6 mice exhibited classical signs associated with cryptococcal meningoencephalitis. Additionally, brain tissues of 5-LO -/- mice exhibited lower levels of cytokines (CCL2 and CCL3) clinically associated with Cryptococcus -related immune reconstitution inflammatory syndrome (C-IRIS). In a systemic mouse model of cryptococcosis, 5-LO -/- mice and those treated with a Federal Drug Administration (FDA)-approved 5-LO synthesis inhibitor, zileuton, displayed significantly reduced mortality compared to C57BL/6 infected mice. These results suggest that therapeutics designed to inhibit host 5-LO signaling could reduce disease pathology and mortality associated with cryptococcal meningoencephalitis., Importance: Cryptococcosis is a mycosis with worldwide distribution and has a broad range of clinical manifestations, including diseases of the CNS. Globally, there is an estimated 179,000 cases of cryptococcal meningitis, resulting in approximately 112,000 fatalities per annum and 19% of AIDS-related deaths. Understanding how host immune responses are modulated during cryptococcosis is central to mitigating the morbidity and mortality associated with cryptococcosis. Leukotrienes (LTs) have been shown to modulate inflammatory responses during infection. In this study, we show that mice deficient in 5-lipoxygenase (5-LO), an enzyme central to the metabolism of arachidonic acid into leukotrienes, exhibit reduced pathology, disease, and neurological signs associated with cryptococcal meningitis. Additionally, mice given an experimental cryptococcal infection and subsequently treated with an FDA-approved 5-LO synthesis inhibitor exhibited significantly reduced mortality rates. These results suggest that therapeutics designed to inhibit host 5-LO activity could significantly reduce pathology and mortality rates associated with cryptococcal meningitis., Competing Interests: The authors declare no conflict of interest.

Fluctuations in genomic repetitive fractions (repeatome) are known to impact several facets of evolution, such as ecological adaptation and speciation processes. Therefore, investigating the divergence of repetitive elements can provide insights into an important evolutionary force. However, it is not clear how the different repetitive element clades are impacted by the different factors such as ecological changes and/or phylogeny. To discuss this, we used the Neotropical legume genus Erythrostemon (Caesalpinioideae) as a model, given its ancient origin (~33 Mya), lineage-specific niche conservatism, macroecological heterogeneity, and disjunct distribution in Meso- and South American (MA and SA respectively) lineages. We performed a comparative repeatomic analysis of 18 Erythrostemon species to test the impact of environmental variables over repeats diversification. Overall, repeatome composition was diverse, with high abundances of satDNAs and Ty3/gypsy-Tekay transposable elements, predominantly in the MA and SA lineages respectively. However, unexpected repeatome profiles unrelated to the phylogeny/biogeography were found in a few MA (E. coccineus, E. pannosus and E. placidus) and SA (E. calycinus) species, related to reticulate evolution and incongruence between nuclear and plastid topology, suggesting ancient hybridizations. The plesiomorphic Tekay and satDNA pattern was altered in the MA-sensu stricto subclade with a striking genomic differentiation (expansion of satDNA and retraction of Tekay) associated with the colonization of a new environment in Central America around 20 Mya. Our data reveal that the current species-specific Tekay pool was the result of two bursts of amplification probably in the Miocene, with distinct patterns for the MA and SA repeatomes. This suggests a strong role of the Tekay elements as modulators of the genome-environment interaction in Erythrostemon, providing macroevolutionary insights about mechanisms of repeatome differentiation and plant diversification across space and time., (© 2024 John Wiley & Sons Ltd.)

Cellular responses to external stress allow microorganisms to adapt to a vast array of environmental conditions, including infection sites. The molecular mechanisms behind these responses are studied to gain insight into microbial pathogenesis, which could lead to new antimicrobial therapies. Here, we explore a role for arrestin protein-mediated ubiquitination in stress response and pathogenesis in the pathogenic fungus Cryptococcus neoformans . In a previous study, we identified four arrestin-like proteins in C. neoformans and found that one of these is required for efficient membrane synthesis, likely by directing interaction between fatty acid synthases and the Rsp5 E3 ubiquitin ligase. Here, we further explore Cn Rsp5 function and determine that this single Ub ligase is absolutely required for pathogenesis and survival in the presence of cellular stress. Additionally, we show that a second arrestin-like protein, Ali2, similarly facilitates interaction between Rsp5 and some of its protein targets. Of the four postulated C. neoformans arrestin-like proteins, Ali2 appears to contribute the most to C. neoformans pathogenesis, likely by directing Rsp5 to pathogenesis-related ubiquitination targets. A proteomics-based differential ubiquitination screen revealed that several known cell surface proteins are ubiquitinated by Rsp5 and a subset also requires Ali2 for their ubiquitination. Rsp5-mediated ubiquitination alters the stability and the localization of these proteins. A loss of Rsp5-mediated ubiquitination results in cell wall defects that increase susceptibility to external stresses. These findings support a model in which arrestin-like proteins guide Rsp5 to ubiquitinate specific target proteins, some of which are required for survival during stress., Importance: Microbial proteins involved in human infectious diseases often need to be modified by specific chemical additions to be fully functional. Here, we explore the role of a particular protein modification, ubiquitination, in infections due to the human fungal pathogen Cryptococcus neoformans . We identified a complex of proteins responsible for adding ubiquitin groups to fungal proteins, and this complex is required for virulence. These proteins are fungal specific and might be targets for novel anti-infection therapy.

The diversification of angiosperms has largely been attributed to adaptive radiation of their pollination and mating systems, which are relevant drivers of the macroevolution processes. The fig (Ficus, Moraceae) and fig wasp (Agaonidae, Hymenoptera) interaction is an example of obligate mutualism. Passive and active pollination modes have been associated with morphological traits in both partners. However, more information is required to assess the relationship between floral traits and pollination modes, particularly in Neotropical Ficus species. This study evaluates the morphological traits of figs and fig wasps regarding pollination modes in species belonging to Neotropical Ficus sections (three species each of Americanae and Pharmacosycea). Pollination mode was identified by floral morphology, anther/ovule ratio, and specialized structures fig wasps use for pollen transport (pollen pocket and coxal combs). Fig species in sect. Americanae are actively pollinated because pistillate flowers form a synstigma, present anther/ovule ratios <0.11, and their pollinator Pegoscapus fig wasps have pollen pockets and coxal combs. In contrast, species in sect. Pharmacosycea have free pistillate flowers, with anther/ovule ratios >0.27; they are pollinated by Tetrapus wasps, which lack specialized structures to carry pollen. Each species of Ficus was associated with a single morphospecies of fig wasp. The results support previous contributions that consider reciprocal morphological traits between fig species and their pollinating wasps as evidence of a close co-evolutionary history., (© 2024 The Author(s). Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC 50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells., (© 2024. The Author(s).)

Background: Despite several studies on the mental health of medical students, there is insufficient research on long-term follow-ups., Aims: To investigate the associated factors and changes in the quality of life and mental health of a group of medical students followed-up for three years., Methods: An observational, prospective cohort study was conducted. Four classes were followed during the first three years of the medical course. The study included sociodemographic data, mental health data using the DASS-21 scale, and quality-of-life data using the WHOQOL-BREF scale. Linear regression models were used for analysis., Results: A total of 201 (66.1%) medical students responded to both data collection waves after a three-year follow-up. Depressive symptoms(p < 0.001), anxiety(p = 0.037), and stress(p < 0.001) increased. Additionally, physical(p < 0.001), psychological(p < 0.001), and social(p = 0.003) quality of life decreased. Worse mental health at baseline and being a woman were associated with worse mental health after three years, while higher income at baseline was associated with better quality of life after three years., Conclusions: The mental health and quality of life of the medical students worsened after three years, being influenced by gender, income, and mental health at baseline. Educators and managers must be aware of these factors to minimize suffering in medical schools.

Background: Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA., Methods: In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing., Findings: We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034)., Interpretation: This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care., Funding: Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

This study evaluated the effect of feeding colostrum obtained from an intramammary administration (IA) of LPS from Escherichia coli (O55:B5) to dairy goats at parturition, on goat kids performance, biochemical parameters (i.e., calcium, LDH, glucose, total proteins, albumin, and urea) and immune status (i.e., IgG and IgM) during the first month of life. At birth, goat kids were weighted (d 0) and immediately allocated into either the LPS group (n = 15) or the CON group (n = 21) based on the experimental group of the dam. At parturition, 20 multiparous dairy goats were allocated in one of the 2 experimental groups (LPS vs. CON). The LPS group received an IA of saline solution (2 mL) containing 50 µg of LPS in each half udder whereas goats in the CON group received an IA of saline solution (2 mL) without LPS. Goat kids were bottle-fed dam colostrum equivalent to 10% of the birth BW divided in 2 meals (i.e., at 3 and 12 h relative to birth), and then fed twice daily with milk replacer ad libitum. Individual milk intake (MI) and BW were recorded on d 7, 15, 21 and 30 of life. Blood samples were collected on d 0, 1, 2, 4, 7, 15, 21 and 30 after birth. Data was analyzed using the MIXED procedure of SAS (9.4). The model included IA, time (T) and the interaction (IA x T) as fixed effects and sex and litter size as random effects. Both groups showed similar MI, except on d 7 relative to birth as the LPS group showed higher MI than the CON group (910.5 ± 69.77 and 683.9 ± 59.64 mL, respectively). No differences in BW or rectal temperature were observed between groups, neither in plasma IgG nor IgM concentrations. Despite the IA did not affect calcium, glucose, LDH, total protein, and albumin concentrations an interaction between the IA and T was observed for urea concentration, showing the LPS group higher urea concentrations than the CON group on d 0 (20.1 ± 1.34 and 20.0 ± 1.25 mg/dL, respectively). In conclusion, feeding colostrum from goats that received an IA of LPS at parturition does not affect goat kid performance, plasma immunoglobulin concentrations and serum metabolites during the first month of life., (© 2024, The Authors. Published by Elsevier 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/).)

Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings., (© 2024. The Author(s).)

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy., Competing Interests: Declaration of interests R.M.-B.: consulting or advisory and/or speaker bureaus for Sanofi Aventis, AstraZeneca, Merck Sharp & Dohme, Astellas, BMS, and travel and accommodation expenses from Roche, Sanofi Aventis, Astellas, Janssen, Merck Sharp & Dohme, Bayer, and Pfizer. J.C. received consulting and speaker’s fees from Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Sanofi, MSD Oncology, Roche, AstraZeneca and Asofarma, and research support from AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals INC, Astellas Pharma., Astrazeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation (BMS), Clovis Oncology INC, Cougar Biotechnology INC, Deciphera Pharmaceuticals LLC, Exelixis INC, F. Hoffmann-La Roche LTD, Genentech INC, Glaxosmithkline, SA, Incyte Corporation, Janssen-Cilag International NV, Karyopharm Therapeutics INC, Laboratoires Leurquin Mediolanum SAS, Lilly SA, Medimmune, Millennium Pharmaceuticals INC., Nanobiotix SA, Novartis Farmacéutica SA, Pfizer, S.L.U, Puma Biotechnology INC, Sanofi-Aventis SA, SFJ Pharma LTD. II, Teva Pharma S.L.U. J.M. has served as advisor for AstraZeneca, Amunix/Sanofi, Daichii-Sankyo, Janssen, MSD; Pfizer and Roche; he is member of the scientific board for Nuage Therapeutics and is involved as investigator in several pharma-sponsored clinical trials, none of them related to this work. He is also the PI of grants funded by AstraZeneca, Amgen, and Pfizer to VHIO (institution), including grant NCR-19-20035, relevant to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC 50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.

Human-induced pressures have led to substantial changes in marine ecosystems worldwide, with the introduction of non-indigenous species (NIS) emerging as a significant threat to ecological, economic, and social aspects. The Macaronesian islands, comprising the Azores, Madeira, Canary Islands, and Cabo Verde archipelagos, are regions where the regional economy is dependent on marine resources (e.g., marine traffic, ecotourism and fisheries). Despite their importance, concerted efforts to manage marine biological invasions in Macaronesia have been scarce. In this context, the current study aims to contribute to the much-needed debate on biosecurity measures in this unique insular ecosystem to prevent and mitigate the impact of NIS. By adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, this work validated and analyzed 260 documents providing insights into the management of NIS in Macaronesia until 2022. These documents revealed the presence of 29 Invasive Alien Species (IAS), most of which are misconceptions regarding this terminology. Most studies focused on the stages of early detection, rapid response, and eradication across the archipelagos. Cabo Verde had comparatively fewer studies. The most common techniques include monitoring/sampling, literature reviews, and taxonomic reviews. NIS introduction pathways were mainly attributed to transport (stowaway) and unaided migration, with ship fouling, ballast water, rafting, ocean currents, and tropicalization being also identified as significant contributors. This systematic review highlights the current efforts to establish robust biosecurity protocols in Macaronesia and emphasizes the urgent need to safeguard the region's ecological, economic, and social well-being., 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.)

Importance: Bovine mastitis, predominantly associated with gram-positive Staphylococcus aureus , poses a significant threat to dairy cows, leading to a decline in milk quality and volume with substantial economic implications., Objective: This study investigated the incidence, virulence, and antibiotic resistance of S. aureus associated with mastitis in dairy cows., Methods: Fifty milk-productive cows underwent a subclinical mastitis diagnosis, and the S. aureus strains were isolated. Genomic DNA extraction, sequencing, and bioinformatic analysis were performed, supplemented by including 124 S. aureus genomes from cows with subclinical mastitis to enhance the overall analysis., Results: The results revealed a 42% prevalence of subclinical mastitis among the cows tested. Genomic analysis identified 26 sequence types (STs) for all isolates, with Mexican STs belonging primarily to CC1 and CC97. The analyzed genomes exhibited multidrug resistance to phenicol, fluoroquinolone, tetracycline, and cephalosporine, which are commonly used as the first line of treatment. Furthermore, a similar genomic virulence repertoire was observed across the genomes, encompassing the genes related to invasion, survival, pathogenesis, and iron uptake. In particular, the toxic shock syndrome toxin ( tss-1 ) was found predominantly in the genomes isolated in this study, posing potential health risks, particularly in children., Conclusion and Relevance: These findings underscore the broad capacity for antibiotic resistance and pathogenicity by S. aureus , compromising the integrity of milk and dairy products. The study emphasizes the need to evaluate the effectiveness of antibiotics in combating S. aureus infections., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain., Methods: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC., Discussion: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine., (© 2024. The Author(s).)

Introduction: Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed graft function has been correlated with less rejection compared to basiliximab, but optimal dosing remains unknown. Program Evaluation Aims: The purpose of this evaluation was to retrospectively assess the short-term effectiveness and tolerability of a clinical protocol that increased the net state of immunosuppression in delayed graft function kidney transplant recipients using cumulative 6 mg/kg rabbit antithymocyte globulin induction. Design: This retrospective cohort included 88 kidney transplant recipients with delayed graft function, transplanted between January 2017 and March 2021, who either received cumulative 4.5 mg/kg pre-protocol or 6 mg/kg post-protocol rabbit antithymocyte globulin. Outcomes evaluated were biopsy-proven acute rejection and incidence of graft loss, infection, and cytopenia at 6 months. Results: A significant reduction of biopsy-proven acute rejection incidence occurred post-protocol implementation (10/33, 30.3% vs 6/55, 10.9%; P  = .04). Of those with rejection, significantly less post-protocol patients were classified as acute cellular rejection (9/10, 90.0% vs 2/6, 33.3%; P  = .04). No death-censored graft loss was observed in either group. Rates of cytopenia and infection were similar pre- versus post-protocol implementation. Conclusion: Increasing the exposure to rabbit antithymocyte globulin and maintenance immunosuppression in delayed graft function kidney transplant recipients was tolerable and significantly reduced rejection occurrence at 6 months., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intrastromal antibiotic injections are a type of treatment that can be very useful in bacterial keratitis refractory to topical antibiotics. We present the case of a 44-year-old woman with an infiltrate in a laser in situ keratomiuleusis (LASIK) flap and growth of Achromobacter xylosoxidans, who was treated with topical ceftazidime for 1 month. However, after discontinuation of the antibiotic, there was a worsening with growth of the same germ. Topical treatment was reintroduced and, due to suspicion of germ reservoir, it was decided to give three cycles of intrastromal ceftazidime injections, the last one also with moxifloxacin, with good results. After 4 months asymptomatic and without treatment at the moment, no signs of recurrence have been observed. This case supports the usefulness of intraestromal injections in refractory cases to the topical medication., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Urinary tract infections (UTIs) are very common worldwide. According to their symptomatology, these infections are classified as pyelonephritis, cystitis, or asymptomatic bacteriuria (AB). Approximately 75-95% of UTIs are caused by uropathogenic Escherichia coli (UPEC), which is an extraintestinal bacterium that possesses virulence factors for bacterial adherence and invasion in the urinary tract. In addition, UPEC possesses type 6 secretion systems (T6SS) as virulence mechanisms that can participate in bacterial competition and in bacterial pathogenicity. UPEC UMN026 carries three genes, namely, ECUMN&#95;0231, ECUMN&#95;0232, and ECUMN&#95;0233, which encode three uncharacterized proteins related to the T6SS that are conserved in strains from phylogroups B2 and D and have been proposed as biomarkers of UTIs., Aim: To analyze the frequency of the ECUMN&#95;0231, ECUMN&#95;0232, ECUMN&#95;0233, and vgrG genes in UTI isolates, as well as their expression in Luria Bertani (LB) medium and urine; to determine whether these genes are related to UTI symptoms or bacterial competence and to identify functional domains on the putative proteins., Methods: The frequency of the ECUMN and vgrG genes in 99 clinical isolates from UPEC was determined by endpoint PCR. The relationship between gene presence and UTI symptomatology was determined using the chi 2 test, with p < 0.05 considered to indicate statistical significance. The expression of the three ECUMN genes and vgrG was analyzed by RT-PCR. The antibacterial activity of strain UMN026 was determined by bacterial competence assays. The identification of functional domains and the docking were performed using bioinformatic tools., Results: The ECUMN genes are conserved in 33.3% of clinical isolates from patients with symptomatic and asymptomatic UTIs and have no relationship with UTI symptomatology. Of the ECUMN + isolates, only five (15.15%, 5/33) had the three ECUMN and vgrG genes. These genes were expressed in LB broth and urine in UPEC UMN026 but not in all the clinical isolates. Strain UMN026 had antibacterial activity against UPEC clinical isolate 4014 (ECUMN - ) and E. faecalis but not against isolate 4012 (ECUMN + ). Bioinformatics analysis suggested that the ECUMN genes encode a chaperone/effector/immunity system., Conclusions: The ECUMN genes are conserved in clinical isolates from symptomatic and asymptomatic patients and are not related to UTI symptoms. However, these genes encode a putative chaperone/effector/immunity system that seems to be involved in the antibacterial activity of strain UMN026., Competing Interests: The authors declare that they have no competing interests., (© 2024 Casiano González et al.)

SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were assessed for circulating anti-SARS-CoV-2 spike IgG levels and avidity for up to 6 months post-primary series and 9 months after the third dose. Following primary series vaccination, anti-SARS-CoV-2 spike IgG levels declined from months 1 to 6, while avidity increased through month 6, irrespective of the vaccine received. The third dose of either vaccine increased anti-SARS-CoV-2 spike IgG levels and avidity and appeared to enhance antibody level persistence-generating a slower rate of decline in the 3 months following the third dose compared to the decline seen after the primary series alone. The third dose of both vaccines induced significant avidity increases 1 month after vaccination compared to the avidity response 6 months post-primary series vaccination ( p ≤ 0.001). A significant difference in avidity responses between the two vaccines was observed 6 months post-third dose, where the BNT162b2 recipients had higher antibody avidity levels compared to the mRNA-1273 recipients ( p = 0.020).

Aims: To explore the influence of gender on periodontal treatment outcomes in a dataset of eight RCTs conducted in Brazil, United States, and Germany., Methods: Clinical parameters were compared between men and women with stages III/IV grades B/C generalized periodontitis at baseline and 1-year post-therapy, including scaling and root planing with or without antibiotics., Results: Data from 1042 patients were analyzed. Men presented a tendency towards higher probing depth (p = .07, effect size = 0.11) and clinical attachment level (CAL) than women at baseline (p = .01, effect size = 0.16). Males also presented statistically significantly lower CAL gain at sites with CAL of 4-6 mm at 1-year post-therapy (p = .001, effect size = 0.20). Among patients with Grade B periodontitis who took antibiotics, a higher frequency of women achieved the endpoint for treatment (i.e., ≤4 sites PD ≥5 mm) at 1 year than men (p < .05, effect size = 0.12)., Conclusion: Men enrolled in RCTs showed a slightly inferior clinical response to periodontal therapy in a limited number of sub-analyses when compared to women. These small differences did not appear to be clinically relevant. Although gender did not dictate the clinical response to periodontal treatment in this population, our findings suggest that future research should continue to explore this topic., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the effect of a rapid training intervention on the knowledge of health providers and the provision of preconception care in primary health care services., Methods: Randomized community trial in eight primary health care facilities (four were randomly allocated to the intervention group and four to the control group) in 2020 in Brazil. The intervention consisted of rapid training in preconception health for all health providers in the intervention group. Health providers who had medicine and nursing backgrounds answered structured questionnaires about their knowledge and practices of preconception health-related topics, and reproductive-age women attending the services completed a questionnaire about their experience with preconception care in pre- and postintervention (three months after the intervention) periods., Findings: The level of knowledge among health providers increased after the intervention, but providing information about preconception care and prescribing folic acid showed no significant change, with the exception of screening for future pregnancy intention., Key Conclusions and Implications for Practice: Although the knowledge of health providers on preconception care is a fundamental requirement for its provision in primary health care settings, rapid training focused on preconception health topics was not sufficient to change their practices, with the exception of pregnancy intention screening, which experienced a slight increase after the training. It appears that additional elements, such as the reorganization of primary health care services to prioritize non-pregnant women, the development and implementation of specific guidelines, along with strategies for the dissemination of preconception care awareness, may also play crucial roles for full preconception care implementation in addition to health providers' knowledge of such issues., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Screen printing is one of the most used techniques for developing printed electronics. It stands out for its simplicity, scalability, and effectivity. Specifically, the manufacturing of hybrid integrated circuits has promoted the development of the technique, and the photovoltaic industry has enhanced the printing process by developing high-performance metallization pastes and high-end screens. In recent years, fine lines of 50 μm or smaller are about to be adopted in mass production, and screen printing has to compete with digital printing techniques such as inkjet printing, which can reach narrower lines. In this sense, this work is focused on testing the printing resolution of a high-performance stainless-steel screen with commercial conductive inks and functional lab-made inks based on reduced graphene oxide using an interdigitated structure. We achieved electrically conductive functional patterns with a minimum printing resolution of 40 μm for all inks., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Salmonella enterica is known for its disease-causing serotypes, including Montevideo and Pomona. These serotypes have been found in various environments, including river water, sediments, food, and animals. However, the global spread of these serotypes has increased, leading to many reported infections and outbreaks. The goal of this study was the genomic analysis of 48 strains of S . Montevideo and S . Pomona isolated from different sources, including clinical. Results showed that environmental strains carried more antibiotic resistance genes than the clinical strains, such as genes for resistance to aminoglycosides, chloramphenicol, and sulfonamides. Additionally, the type 4 secretion system, was only found in environmental strains. .Also many phosphotransferase transport systems were identified and the presence of genes for the alternative pathway Entner-Doudoroff. The origin of isolation may have a significant impact on the ability of Salmonella isolates to adapt and survive in different environments, leading to genomic flexibility and a selection advantage.

Prosthetic biomaterials can affect the composition of the subgingival microbiota and consequently the production of proinflammatory cytokines, causing damage to the periodontium. A total of 40 patients were divided into two groups: 20 with monolithic zirconia (MZ) prostheses and 20 with porcelain fused to metal (PFM) with nickel-chromium (Ni-Cr) alloy prostheses. Subgingival plaque and gingival crevicular fluid samples were taken. The Checkerboard technique for DNA-DNA hybridization and the enzyme-linked immunosorbent assay technique were performed. Teeth with MZ presented a lower percentage of bleeding on probing and tooth mobility compared to teeth with PFM with Ni-Cr alloy. Prosthodontic teeth harbored higher total levels of the 18 bacterial species than non-prosthodontic teeth. There was a higher prevalence of S. gordonii and V. parvula species in PFM with Ni-Cr alloy compared to MZ. There was an increase in IL-1β, TNF-α and CX3CL1 levels in PFM with Ni-Cr alloy compared to MZ. MZ is a candidate biomaterial with fewer negative effects on the periodontium, allowing for longer prostheses longevity in the mouth.

Yeast infections are challenging human and animal medicine due to low rates of detection and the emergence of unknown ecology isolates. The aim of this study was to verify the biochemical identification of yeasts and yeast-like microorganisms obtained from animals comparing the results with chromogenic media and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS). Between January and August 2023, yeast and yeast-like isolates from samples of animals with suspicion of mycosis were identified using Vitek ® 2 Compact, Brilliance ® Candida Agar and MALDI Biotyper ® MSP. A total of 39 cases were included, and 45 isolations were obtained. Cryptococcus neoformans (15.5%, 7/45), Meyerozyma guilliermondii (13.3%, 6/45), Candida parapsilosis (11.1%, 5/45), Candida albicans and Candida tropicalis (8.9%, each one 4/45) were the most identified organisms. There was full agreement with the three identification methods in 71.1% (32/45) of the isolates, disagreement on species in 17.8% (8/45), disagreement on genus and species in 6.7% (3/45) and, in 4.4% (2/45), there was no matched pattern in MALDI-TOF to compare the results. Biochemical methods are a good option in laboratories where proteomics are not available, and chromogenic media enhances diagnostics by detecting mixed infections. Surveillance must be implemented to improve the detection of agents shared between humans and animals.