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Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC with patients with average onset colorectal cancer (AO-CRC) to help define surveillance outcomes in these groups. Single-institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps [adenoma/sessile serrated]) were examined. For each group, 3 serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards. A total of 1259 patients with CRC were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared with patients with AO-CRC, patients with EO-CRC had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (hazard ratio, 0.71; 95% confidence interval, 0.52–1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (P =.003), and patients with EO-CRC were found to have less advanced neoplasia compared with their counterparts with AO-CRC (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that, while patients with EO-CRC returned for follow-up surveillance colonoscopy earlier than patients with AO-CRC, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas. Patients with EO-CRC do not have an increased risk of advanced neoplasia compared with patients with AO-CRC and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend. [ABSTRACT FROM AUTHOR]

EMR and endoscopic submucosal dissection (ESD) are both accepted resection strategies for Barrett's esophagus–related neoplasia and esophageal adenocarcinoma (EAC). However, a lack of consensus exists regarding which technique offers superior outcomes. This study aims to systematically review the evidence comparing EMR versus ESD in treating Barrett's neoplasia and EAC. We searched 3 databases (Embase, MEDLINE, Cochrane Central) through October 2023. We included studies comparing the efficacy of EMR and ESD for Barrett's neoplasia and EAC. Primary outcomes include en bloc, R0, and curative resection; complete remission of dysplasia (CRD), and local recurrence. Secondary outcomes encompass adverse events. Our search identified 905 records. Eleven studies were included in the final analyses. Data showed significantly higher en bloc resection rates with ESD (odds ratio [OR], 31.53; 95% confidence interval [CI], 10.02-99.19; P <.01; 7 studies). R0 resection rates were significantly higher with ESD (OR, 5.92; 95% CI, 2.75-12.77; P <.01; 8 studies). Curative resection rates tended to be higher with ESD (OR, 3.49; 95% CI, 0.86-14.14; P =.080; 4 studies). There was no significant difference in CRD rates (OR, 0.92; 95% CI, 0.37-2.26; P =.86; 3 studies). Local recurrence rates tended to be lower with ESD (OR, 0.35; 95% CI, 0.11-1.04; P =.058; 10 studies). As for adverse events, there was no significant difference in bleeding, perforation, and postoperative stricture rates. This systematic review and meta-analysis demonstrates that ESD achieves higher en bloc, R0, and curative resection rates, with a tendency toward lower recurrence rates. These results suggest that ESD may be a more effective option for managing Barrett's neoplasia and EAC. (International Prospective Register of Systematic Reviews [PROSPERO] registration number: CRD42023426486.) [Display omitted] [ABSTRACT FROM AUTHOR]

The laboratory measurements conducted on Vaca Muerta formation samples demonstrate stress-dependent elastic behavior and compaction under representative in situ conditions. The experimental results reveal that the analyzed samples display elastoplastic deformation and shear-enhanced compaction as primary plasticity mechanisms. These experimental findings contradict the expected linear elastic response anticipated before brittle failure, as reported in several studies on the geomechanical characterization of the Vaca Muerta formation. Therefore, we present a comprehensive laboratory analysis of Vaca Muerta formation samples showing their nonlinear elastic behavior and irrecoverable shear-enhanced compaction. Additionally, we calibrate an elastoplastic constitutive model based on these experimental observations. The resulting model accurately reproduces the observed phenomena, playing a pivotal role in geoengineering applications within the energy industry.

Nowadays, many wireless applications require the exchange of electromagnetic waves through propagation environments that look like to stratified media to some extent. This may concern both natural scenarios, e.g., air/vegetation/ground, and artificial structures, like meta-materials, photonic devices, solar cells or systems-on-chip. The characterization of the layered propagation channel is therefore important for the design and deployment of effective devices and systems. To this aim, the Dyadic Green Function method has been often leveraged, although its use is usually limited to simple sources, like short dipoles or current elements. Furthermore, it seems unsuited to assess the dispersive properties of the channel, which are known to become important when high data-rate must be conveyed. In this paper, a ray-based approach to propagation inside layers is proposed. As the layered environment can be quite reverberating, a great number of rays may be needed, to the extent that the corresponding computational burden might be hardly afforded by general purpose ray tracing tools. Therefore, the ray tracing engine here presented is specifically conceived for the layered case, and mostly relies on analytical formulation. The accuracy of the model is checked against measurement carried out at chip scale at optical frequency, as a reference study case.

Introduction It is well known that eating disorders are related to comorbidity. At least, half of these patients have other mental disorders and, in addition to it, the presence of physical comorbidity (cardiovascular, kidney, nervous system, digestive tract, metabolic or endocrine disorders) comes with a decline in life expectancy. Objectives Description of a patient with a diagnosis of anorexia nervosa (AN) who developed a gastric bezoar during hospitalization. Methods Case treated in a specific Eating Disorder Unit in a Third-Level Hospital. Results 26 years old woman with a diagnosis of AN hospitalized in General Psychiatric Unit with BMI of 11,78 kg/m2. Nasogastric tube was necessary and, after 1 month with a progressive weight recovery (BMI 13,84 kg/m2), the patient was transferred to the Eating Disorder Unit in order to follow specific psychological therapy. No incidence related to physical exploration or clinical analyses happened during this month apart from pancytopenia due to malnutrition. However, 8 days after, patient developed nausea and had 3 vomit episodes, constant abdominal pain at hipogastrium (moderate intensity), dizziness, instability and constipation. The patient refused possibility of pregnancy. The physical exam showed bowel sounds augmented but no mass or peritoneal irritation appeared. Blood test results were normal. Abdominal X-Ray showed gastric dilatation with small bowel faeces sign, which suggested diagnosis of gastric bezoar. The treatment was the dissolution of the bezoar by Coca-Cola, solving the symptoms completely. The patient refused having eaten hair or any other kind of object or indigestible material but admitted to be following a strict vegan diet. Finally, after an endoscopy was done, the patient was diagnosed of phytobezoar. Conclusions Based on literature, bezoars are rare in AN, being phytobezoars the most common between the types of bezoars. Nevertheless, there are some risk factors, such as delayed gastric emptying, dehydration or, in the case of phytobezoar, ingestion of food containing high amount of cellulose, hemi-cellulose, lignin, and tannins (celery, pumpkin, grape skins, prunes, raisins and, in particular, persimmons). Some of the symptoms caused by phytobezoar can be similar to those of the AN (abdominal pain, intestinal obstruction, poor appetite, vomiting, malnutrition, weight loss). Therefore, gastric bezoar could be an underdiagnosed or even undiagnosed disease in this group of patients. Taking this into account could reduce time until diagnosis and treatment, decreasing the risks associated. Disclosure of Interest None Declared

Introduction Chronic insomnia, resistant to different treatments (pharmacological, sleep hygiene and cognitive-behavioral therapy) remains one of the greatest challenges in our daily practice as psychiatrists. The pharmacological options include benzodiazepines and their analogues (zolpidem, zopiclone, etc.). However, when trying to treat chronic insomnia the use of off-label drugs, including antidepressants with sedative action (such as trazodone), antipsychotics or antiepiletic drugs, is not uncommon. Perampanel is a non-competitive AMPA receptor antagonist, marketed for the treatment of partial onset epilepsy and primary generalized tonic-clonic seizures. It has been used in the treatment of chronic insomnia with positive results and it has shown to improve the quality of sleep in a recent observational retrospective cohort study. The most frequent adverse effects of Perampanel include dizziness and drowsiness. Perampanel can also cause psychiatric and behavioral adverse effects, aggression and irritability in up to 10% of patients, as well as depression, and suicidal ideation, with higher rates in patients with psychiatric history. Objectives To draw attention to possible adverse effects of Perampanel and to add knowledge to improve the treatment for chronic insomnia. Methods Case report and non-systematic literature review of the current data. Results A 33 year old woman with Anorexia Nervosa was admitted to the psychiatric hospitalization unit due to suicidal ideation and a history of chronic insomnia. Perampanel was started at a dose of 2mg/day, progressively titrated to 6mg/day, following patient’s informed consent. A week after the initiation of treatment, her sleep pattern had improved but she became aggressive, showed low tolerability to minor frustrations and suffered from an intensification of suicidal ideation. She became extremely hostile to the personnel, had severe tantrums and deliberate self injurious behavior. Perampanel was discontinued and in less than a week her aggressive behavior succumbed. Although she was not re-exposed to Perampanel the symptoms she presented are considered a very likely adverse drug reaction. Levomepromazine 20mg/day and Lormetazepam 0.5mg/day were reinstated as a treatment for insomnia. Conclusions Psychiatric comorbidity is known to be a risk factor for behavioral adverse effects of Perampanel. Therefore Perampanel as a treatment for chronic insomnia needs a careful individual benefit-risk assessment and monitoring for adverse effects. Disclosure of Interest None Declared

Whole-Body Electromyostimulation (WB-EMS) is a training technology that enables simultaneous stimulation of all the main muscle groups with a specific impulse intensity for each electrode. The corresponding time-efficiency and joint-friendliness of WB-EMS may be particularly attractive for people unable or unmotivated to conduct (intense) conventional training protocols. However, due to the enormous metabolic and musculoskeletal impact of WB-EMS, particular attention must be paid to the application of this technology. In the past, several scientific and newspaper articles reported severe adverse effects of WB-EMS. To increase the safety of commercial non-medical WB-EMS application, recommendations “for safe and effective whole-body electromyostimulation” were launched in 2016. However, new developments and trends require an update of these recommendations to incorporate more international expertise with demonstrated experience in the application of WB-EMS. The new version of these consensus-based recommendations has been structured into 1) “general aspects of WB-EMS”, 2) “preparation for training”, recommendations for the 3) “WB-EMS application” itself and 4) “safety aspects during and after training”. Key topics particularly addressed are 1) consistent and close supervision of WB-EMS application, 2) mandatory qualification of WB-EMS trainers, 3) anamnesis and corresponding consideration of contraindications prior to WB-EMS, 4) the participant’s proper preparation for the session, 5) careful preparation of the WB-EMS novice, 6) appropriate regeneration periods between WB-EMS sessions and 7) continuous interaction between trainer and participant at a close physical distance. In summary, we are convinced that the present guideline will contribute to greater safety and effectiveness in the area of non-medical commercial WB-EMS application.

The mu opioid receptor agonists are the most efficacious pain controlling agents but their use is accompanied by severe side effects. More recent developments indicate that some ligands can differentially activate receptor downstream pathways, possibly allowing for dissociation of analgesia mediated through the G protein from the opioid-related side effects mediated by β-arrestin pathway. In an effort to identify such biased ligands, here we present a series of thirteen endomorphin-2 (EM-2) analogs with modifications in positions 1, 2, and/or 3. All obtained analogs behaved as mu receptor selective agonists in calcium mobilization assay carried out on cells expressing opioid receptors and chimeric G proteins. A Bioluminescence Resonance Energy Transfer (BRET) approach was employed to determine the ability of analogs to promote the interaction of the mu opioid receptor with G protein or β-arrestin 2. Nearly half of the developed analogs showed strong bias towards G protein, in addition four compounds were nearly inactive towards β-arrestin 2 recruitment while blocking the propensity of EM-2 to evoke mu-β-arrestin 2 interaction. The data presented here contribute to our understanding of EM-2 interaction with the mu opioid receptor and of the transductional propagation of the signal. In addition, the generation of potent and selective mu receptor agonists strongly biased towards G protein provides the scientific community with novel tools to investigate the in vivo consequences of biased agonism at this receptor.

A claimed technological advantage of online professional development (OPD) is the flexibility for educators to learn at a time and space of their convenience. However, the question of how, and with whom educators learn in OPD has received limited empirical attention. Using a participatory design approach, we explored the lived experiences and social networks of 19 educators following a formal OPD in a microcredential format. The mixed method study findings indicated that most (but not all) educators developed learning ties with their peers. This suggests that additional structural opportunities are needed to maintain social engagement in OPD. The findings will be of interest primarily to educators developing and delivering OPD, as well as current or potential professional learners who want to make the most out of OPD.

BackgroundScientists and practitioners alike need reliable, valid measures of contextual factors that influence implementation. Yet, few existing measures demonstrate reliability or validity. To meet this need, we developed and assessed the psychometric properties of measures of several constructs within the Inner Setting domain of the Consolidated Framework for Implementation Research (CFIR).MethodsWe searched the literature for existing measures for the 7 Inner Setting domain constructs (Culture Overall, Culture Stress, Culture Effort, Implementation Climate, Learning Climate, Leadership Engagement, and Available Resources). We adapted items for the healthcare context, pilot-tested the adapted measures in 4 Federally Qualified Health Centers (FQHCs), and implemented the revised measures in 78 FQHCs in the 7 states (N = 327 respondents) with a focus on colorectal cancer (CRC) screening practices. To psychometrically assess our measures, we conducted confirmatory factor analysis models (CFA; structural validity), assessed inter-item consistency (reliability), computed scale correlations (discriminant validity), and calculated inter-rater reliability and agreement (organization-level construct reliability and validity).ResultsCFAs for most constructs exhibited good model fit (CFI > 0.90, TLI > 0.90, SRMR

La relación entre cuidado y tecnociencia genera un campo de estudios muy dinámico en las ciencias sociales, como el proyecto en que se inscriben los resultados aquí presentados (anonimizado). En este artículo se analizan las implicaciones que las tecnologías tienen en el trabajo concreto del Servicio de Ayuda a Domicilio (SAD). Para ello, se ha llevado a cabo una aproximación cualitativa longitudinal mediante entrevistas a auxiliares del SAD a través de cuyos discursos se estudia cómo se reconfiguran las prácticas del cuidado con las tecnologías, tras la irrupción de la pandemia. Otros objetivos que centran el análisis son conocer los requerimientos en términos de competencias, habilidades y destrezas que —la nueva situación— requiere movilizar así como las exigencias que conlleva; e identificar de qué modo contribuyen a definir el cuidado con las tecnologías en un espacio que tiende a resistirse a los cambios como es el ámbito doméstico.

Abstract Background With the gradual resumption of sports activities after the lock-down period for coronavirus pandemic, a new problem is emerging: Allow all athletes to be able to return to compete after SARS-CoV-2 infection in total safety. Several protocols have been proposed for healed athletes but all of them have been formulated for the adult population. The aim of the present study is to evaluate the adequacy of Italian practical recommendations for return-to-paly, in order to exclude cardiorespiratory complications due to COVID-19 in children and adolescents. Methods Between April 2020 and January 2021 the Italian Sports Medical Federation formulated cardiorespiratory protocols to be applied to athletes recovered from SARS-CoV-2 infection. The protocols take into account the severity of the infection. Protocols include lung function tests, cardiopulmonary exercise test, echocardiographic evaluation, blood chemistry tests. Results From September 2020 to February 2021, 45 children and adolescents (aged from 9 to 18 years; male = 26) with previous SARS-CoV-2 infection were evaluated according to the protocols in force for adult. 55.5% of the subjects (N = 25) reported an asymptomatic infection; 44.5% reported a mild symptomatic infection. Results of lung function test have exceeded the limit of 80% of the theoretical value in all patients. The cardiorespiratory capacity of all patients was within normal limits (average value of maximal oxigen uptake 41 ml/kg/min). No arrhythmic events or reduction in the ejection fraction were highlighted. Conclusion The data obtained showed that, in the pediatric population, mild coronavirus infection does not cause cardiorespiratory complications in the short and medium term. Return to play after Coronavirus infection seems to be safe but it will be necessary to continue with the data analysis in order to modulate and optimize the protocols especially in the pediatric field.

El aparecer en la Educación a Distancia nuevos horizontes trajo consigo, por la complejidad, las dimensiones y la envergadura de los mismos, toda una serie de dificultades detectadas a través de observaciones, y experiencia profesional, las cuales proyecta resolver mediante una estrategia general de gestión del aprendizaje organizada en acciones que deben ejecutar los principales actores del proceso, validada mediante criterio de especialista y criterio de usuario con resultados significativos y se concluye que la gestión del aprendizaje es un proceso complejo que requiere del trabajo coordinado de todos los que inciden directa e indirectamente en el estudiante y que el trabajo metodológico y la autopreparación del docente y del estudiante constituyen la esencia de la gestión del aprendizaje en la Educación a Distancia.

Na história antiga de Portugal e da Galiza há um consenso consistente na ideia de que o nome da comum região Callaecia derivou, em época romana inicial, de um povo de Callaeci epónimos assentados na margem direita da foz do Douro. Este consenso pode ser categorizado como questão eponímica. Apesar de que tal questão sofreu uma forte variabilidade de interpretações, um artigo de 1977 de A. Tranoy assentou a sua forma actual e o consenso hoje existente sobre ela. Mas tal consenso limitou-se à aceitação acrítica das teses de A. Tranoy, que não foram revisitadas desde então. O presente artigo re-examina as provas da questão eponímica e demonstra a sua fraqueza, junto com a necessidade de ampliar as perspectivas sobre o suposto povo epónimo e as origens do paleo-corónimo regional.

Background: Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothelial cell activation, proliferation, and migration. The effect of opioids on this process is controversial with no data for NOP receptor ligands. Methods: We used patient-derived human umbilical vein endothelial cells (HUVECs) treated with media from the Michigan Cancer Foundation-7 (MCF-7) breast cancer cells or vascular endothelial growth factor (VEGF; 10 ng ml−1) and fibroblast growth factor (FGF; 10 ng ml−1) as angiogenic stimuli. We have measured (i) NOP/MOP messenger RNA, (ii) receptor protein using N/OFQATTO594 and DermorphinATTO488 as fluorescent probes for NOP and MOP, and (iii) NOP/MOP function in a wound healing assay (crude measure of migration that occurs during angiogenesis). Results: HUVEC lines from 32 patients were used. Using all 32 lines, mRNA for NOP but not MOP was detected. This was unaffected by media from MCF-7 cells or VEGF/FGF. There was no binding of either N/OFQATTO594(NOP) or DermorphinATTO488(MOP) in the absence or presence of angiogenic stimuli (six lines tested). In the absence of MOP mRNA, this was expected. Whilst MCF-7 conditioned medium (not VEGF/FGF) reduced wound healing per se (14 lines tested), there was no effect of N/OFQ (NOP ligand) or morphine (MOP ligand). Conclusions: Media from MCF-7 breast cancer cells or VEGF/FGF as angiogenic stimuli did not influence NOP translation into receptor protein. MOP was absent. In the absence of constitutive or inducible MOP/NOP, there was no effect on wound healing as a measure of angiogenesis.

Purpose Exposure to different types of vaccine information in social media can result in parents making disparate vaccine decisions, including not following national guidelines for human papillomavirus (HPV) vaccination. We sought to characterize parents’ exposure to and engagement with information about HPV vaccination in social media, and the associations between exposure to such information and vaccine decisions for their adolescent children. Methods In 2019, we conducted a web-based survey with a national sample of 1073 parents of adolescents who use social media. The survey assessed whether parents have seen information in favor, against, or mixed about HPV vaccination. Multivariable logistic regressions assessed correlates of vaccine decisions, including HPV vaccine initiation, delay, and refusal. Results Sixty-one percent of parents reported that their children have initiated HPV vaccination. Over one-third of parents (37%) reported seeing HPV vaccine information on social media, which was either in favor (20%), against (5%), or a mix (12%). Parents exposed to information in favor were more likely than those who saw no information to have initiated HPV vaccination (OR = 1.74, 95% CI:1.24, 2.44). Parents exposed to information against vaccination were more likely to have delayed (OR = 3.29, 95% CI:1.66, 6.51) or refused (OR = 4.72, 95% CI:2.35, 9.50) HPV vaccination. Exposure to mixed information was also significantly associated with vaccine delay and refusal. Discussion Our findings suggest that the type of information seen on social media regarding HPV vaccination may influence the decisions parents make about vaccinating their children. Efforts should be sought to increase online information in favor of HPV vaccination and combat vaccine misinformation in social media.

Extracellular vesicles released by the primary pathogen of periodontal disease Porphyromonas gingivalis (Pg), referred to as outer membrane vesicles (OMVs), have been associated with the pathogenesis of systemic diseases like cardiovascular disease, rheumatoid arthritis, and Alzheimer’s disease. A pathogenic role for Pg by disrupting placental homeostasis was proposed in the association between periodontal disease and adverse pregnancy outcomes. On the basis that trophoblast-derived factors modulate endothelial and immune cell profiles in normal pregnancy and the scarce presence of Pg in placenta, we hypothesized that OMVs from Pg affect trophoblast cell phenotype, impairing trophoblast–endothelium and trophoblast–neutrophil interactions. By means of in vitro designs with first-trimester human trophoblast cells, endothelial cells, and freshly isolated neutrophils, we showed that Pg OMVs are internalized by trophoblast cells and modulate the activity and expression of functional markers. Trophoblast cells primed with Pg OMVs enhanced neutrophil chemoattraction and lost their anti-inflammatory effect. In addition, reduced migration with enhanced adhesion of monocytes was found in endothelial cells upon incubation with the media from trophoblast cells pretreated with Pg OMVs. Taken together, the results support a pathogenic role of Pg OMVs at early stages of pregnancy and placentation through disruption of trophoblast contribution to vascular transformation and immune homeostasis maintenance.

HPV vaccination is recommended for U.S. adolescents at ages 11–12 and requires two versus three doses if the series is started before age 15. We evaluated how talking about recommended age or fewer doses motivates on-time HPV vaccination. Our national, online experiment randomized 1,263 parents of adolescents to view one of three messages about HPV vaccination recommendations or no message. Messages framed guidelines as recommending: vaccination at age 11–12; fewer doses for those who start vaccination at age 11–12; or, fewer doses for those who start vaccination before age 15. We then assessed parents’ preferred age for HPV vaccination, categorizing preferences of ≤12 years as on-time. Parents who viewed “at age 11–12” versus no message more often preferred on-time HPV vaccination (63% vs. 43%, p .05). Parents who viewed “fewer doses before age 15” less often preferred on-time HPV vaccination (39%, p

The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Low complexity regions (LCRs) play a role in a variety of important biological processes, yet we lack a unified view of their sequences, features, relationships, and functions. Here, we use dotplots and dimensionality reduction to systematically define LCR type/copy relationships and create a map of LCR sequence space capable of integrating LCR features and functions. By defining LCR relationships across the proteome, we provide insight into how LCR type and copy number contribute to higher order assemblies, such as the importance of K-rich LCR copy number for assembly of the nucleolar protein RPA43 in vivo and in vitro. With LCR maps, we reveal the underlying structure of LCR sequence space, and relate differential occupancy in this space to the conservation and emergence of higher order assemblies, including the metazoan extracellular matrix and plant cell wall. Together, LCR relationships and maps uncover and identify scaffold-client relationships among E-rich LCR-containing proteins in the nucleolus, and revealed previously undescribed regions of LCR sequence space with signatures of higher order assemblies, including a teleost-specific T/H-rich sequence space. Thus, this unified view of LCRs enables discovery of how LCRs encode higher order assemblies of organisms.

Abstract Assumptions about how conservation practices will affect ecological outcomes are critical for informing and learning from conservation actions. However, when assumptions do not reflect conditions to which they are applied, they can impede achievement of targeted outcomes and hinder capacity to contribute to conservation goals. We assert that identifying and examining technical assumptions, or those that relate to abiotic or biotic systems, in conservation practice retrospectively for broad conservation strategies is crucial for advancing learning in conservation. Unlike existing proactive assumption frameworks, retroactive examination, which is often realistic for broad scale conservation, allows for honest evaluation of the contributions of those strategies toward shared goals. We propose the state, identify, focus, and think (SIFT) framework, a four‐step process, to guide examination of technical assumptions by defining how assumptions interact with biological circumstances to shape outcomes. We demonstrate use of the SIFT framework with a common technical assumption in US federal private lands conservation programs—that all acres are similarly valuable for achieving wildlife conservation benefits. With the SIFT framework, we show that the benefits of these programs are likely to be applicable to mobile, generalist species with small space requirements, while many species of conservation concern are less likely to benefit.

Objective: To evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. Methods: A retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR ( 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR

Congenital cytomegalovirus (cCMV) infection can follow primary and secondary maternal infection. Growing evidence indicate that secondary maternal infections contribute to a much greater proportion of symptomatic cCMV than was previously thought. We performed a monocentric retrospective study of babies with cCMV evaluated from August 2004 to February 2021; we compared data of symptomatic children born to mothers with primary or secondary infection, both at birth and during follow up. Among the 145 babies with available data about maternal infection, 53 were classified as having symptomatic cCMV and were included in the study: 40 babies were born to mothers with primary infection and 13 babies were born to mothers with secondary infection. Analyzing data at birth, we found no statistical differences in the rate of clinical findings in the two groups, except for unilateral sensorineural hearing loss (SNHL) which was significantly more frequent in patients born to mother with secondary infection than in those born to mother with primary infection (46.2 vs. 17.5%, P = 0.037). During follow up, we found a higher rate of many sequelae (tetraparesis, epilepsy, motor and speech delay, and unilateral SNHL) in the group of children born to mothers with secondary infection, with a statistical difference for tetraparesis and unilateral SNHL. Otherwise, only children born to mothers with primary infection presented bilateral SNHL both at birth and follow up. Our data suggest that the risk of symptomatic cCMV and long-term sequelae is similar in children born to mother with primary and secondary CMV infection; it is important to pay appropriate attention to seropositive mothers in order to prevent reinfection and to detect and possibly treat infected babies.

IntroductionPredictors of late life-threatening arrhythmic events in Brugada syndrome (BrS) patients who received a prophylactic ICD implantation remain to be evaluated. The aim of the present long-term multicenter study was to assess the incidence and clinical-electrocardiographic predictors of late life-threatening arrhythmic events in BrS patients with a prophylactic implantable cardioverter defibrillator (ICD) and undergoing generator replacement (GR).MethodsThe study population included 105 patients (75% males; mean age 45 ± 14years) who received a prophylactic ICD and had no arrhythmic event up to first GR.ResultsThe median period from first ICD implantation to last follow-up was 155 (128–181) months and from first ICD Implantation to the GR was 84 (61–102) months. During a median follow-up of 57 (38–102) months after GR, 10 patients (9%) received successful appropriate ICD intervention (1.6%/year). ICD interventions included shock on ventricular fibrillation (n = 8 patients), shock on ventricular tachycardia (n = 1 patient), and antitachycardia pacing on ventricular tachycardia (n = 1 patient). At survival analysis, history of atrial fibrillation (log-rank test; P = 0.02), conduction disturbances (log-rank test; P < 0.01), S wave in lead I (log-rank test; P = 0.01) and first-degree atrioventricular block (log-rank test; P = 0.04) were significantly associated with the occurrence of late appropriate ICD intervention. At Cox-regression multivariate analysis, S-wave in lead I was the only independent predictor of late appropriate ICD intervention (HR: 9.17; 95%CI: 1.15–73.07; P = 0.03).ConclusionsThe present study indicates that BrS patient receiving a prophylactic ICD may experience late appropriate intervention after GR in a clinically relevant proportion of cases. S-wave in lead I at the time of first clinical evaluation was the only independent predictor of persistent risk of life-threatening arrhythmic events. These findings support the need for GR at the end of service regardless of previous appropriate intervention, mostly in BrS patients with conduction abnormalities.

This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3–7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non–COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non–COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non–COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium, Fusobacterium, and Neisseria and reduced in Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, and Akkermansia, compared with CTRLs (p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non–COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort (p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella, Clostridium, Dialister, Ruminococcus, and Streptococcus and a decrease of Bifidobacterium, Blautia, Granulicatella, and Prevotella, compared with CTRLs. Stratifying for disease severity, the GM associated to “moderate” COVID-19 was characterized by lower α-diversity compared with “mild” and “asymptomatic” and by a GM profile deprived in Neisseria, Lachnospira, Streptococcus, and Prevotella and enriched in Dialister, Acidaminococcus, Oscillospora, Ruminococcus, Clostridium, Alistipes, and Bacteroides. The ML models identified Staphylococcus, Anaerostipes, Faecalibacterium, Dorea, Dialister, Streptococcus, Roseburia, Haemophilus, Granulicatella, Gemmiger, Lachnospira, Corynebacterium, Prevotella, Bilophila, Phascolarctobacterium, Oscillospira, and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)–based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients’ GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2–infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19–related GM.

Background In September 2017, hurricanes Irma and Maria affected Puerto Rico (PR) and the US Virgin Islands (USVI), causing major disruptions in basic services and health care. This study documented the stressors and experiences of patients with gynecologic cancer receiving oncology care in PR following these hurricanes. Methods We conducted 4 focus groups (December 2018-April 2019) among women aged ≥21 years from PR who were diagnosed with gynecological cancer between September 2016 and September 2018 (n = 24). Using the same eligibility criteria, we also interviewed patients from the USVI (n = 2) who were treated in PR. We also conducted key-informant interviews with oncology care providers and administrators (n = 23) serving gynecologic cancer patients in PR. Discussions were audio-recorded, transcribed verbatim, and coded to identify emergent themes using a constant comparison method. Results Analyses of focus group discussions and interviews allowed us to identify the following emergent themes: 1) disruptions in oncology care were common; 2) communication between oncology providers and patients was challenging before and after the hurricanes hit; 3) patient resilience was key to resume care; and 4) local communities provided much-needed social support and resources. Conclusions This study provides firsthand information about the disruptions in oncology care experienced by and the resiliency of women with gynecologic cancer following hurricanes Irma and Maria. Our findings underscore the need to incorporate oncology care in the preparedness and response plans of communities, health systems, and government agencies to maintain adequate care for cancer patients during and after disasters such as hurricanes.

It is currently unknown the most effective potentiation protocol to increase maximum strength. Hence, we investigated the separated and combined effects of post-tetanic potentiation (PTP) induced by whole body electrostimulation (WB-EMS) and post-activation potentiation (PAP) induced by voluntary maximum isometric contractions on maximum isometric strength. Ten trained males were randomly evaluated on four occasions. In session A, maximum isometric strength (split squat) was measured in minutes 1, 4, and 8. In session B, the measurements were taken in minutes 2, 6, and 10. In session C, a WB-EMS protocol was applied to elicit PTP and the measurements were performed in minutes 1, 4, and 8. In session D, the same WB-EMS protocol was applied and the measurements were taken in minutes 2, 6, and 10. No significant differences in maximum isometric strength were observed between: (i) the control and WB-EMS in minutes 1 vs. 1 and 2 vs. 2; (ii) the control and PAP in minutes 1 vs. 4, 1 vs. 8, 2 vs. 6, and 2 vs. 10; and (iii) the PAP and WB-EMS plus PAP in minutes 4 vs. 4, 8 vs. 8, 6 vs. 6, and 10 vs. 10. In contrast, the WB-EMS plus PAP revealed a significant increase of 54% (~450 N) compared to the WB-EMS in minutes 4 and 8 compared to the minute 1 (p < 0.001), but not between minutes 2 vs. 6 and 2 vs. 10. The present results showed that PTP induced by WB-EMS in isolation or combined with PAP induced by voluntary maximum isometric contractions did not produce a significant increase in maximum isometric strength compared to the control and PAP alone, respectively.