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ObjectiveThe cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation within a sample of US mothers.MethodsParticipants were drawn from a previous study of human milk cytokines. The present analysis includes 162 participants (98 Black, 64 White) with infants ranging from 1 to 18 months of age. Levels of cytokines were determined previously. Here we measure milk sodium (Na) and potassium (K) levels with ion-selective probes. Two approaches were used to define elevated MEP: Na levels ≥10 mmol/L and Na/K ratios greater than 0.6. Associations between maternal–infant characteristics, elevated MEP, and twelve analytes (IL-6, IL-8, TNFα, IL-1β, FASL, VEGFD, FLT1, bFGF, PLGF, EGF, leptin, adiponectin) were examined using bivariate associations, principal components analysis, and multivariable logistic regression models.ResultsElevated MEP was observed in 12 and 15% of milk samples as defined by Na and Na/K cutoffs, respectively. The odds of experiencing elevated MEP (defined by Na ≥ 10 mmol/L) were higher among Black participants and declined with older infant age. All cytokines, except leptin, were positively correlated with either Na or the Na/K ratio. A pro-inflammatory factor (IL-6, IL-8, TNFα, IL-1β, EGF) and a tissue remodeling factor (FASL, VEGFD, FLT1, bFGF, PLGF, adiponectin) each contributed uniquely to raising the odds of elevated MEP as defined by either Na or the Na/K ratio.ConclusionThis exploratory analysis of MEP and cytokine levels during established lactation indicates that elevated MEP may be more common in US populations than previously appreciated and that individuals identifying as Black may have increased odds of experiencing elevated MEP based on current definitions. Research aimed at understanding the role of MEP in mammary gland health or infant growth and development should be prioritized.

Ecological and environmental crises are related to the development of an anthropocentric human culture. They threaten the values on which human life and development on Earth depend, and therefore the need for a new ethic arises. The aim of this paper, which is based on a qualitative analysis of theoretical sources, is to highlight the gravity of these crises and to present a 'new ethics', which is referred to as the ethics of the future, the ethics of responsibility for the future or the ethics of sustainability. We draw on the work of H. Jonas and other thinkers who point out that the traditional ethics, which is also referred to as anthropocentric, is no longer sufficient in today's world. It cannot contribute to solving these crises. We argue in favour of a 'new ethics' that takes into account the distant future and relies on a new dimension of responsibility, but also of justice. It urges people to be able to take responsibility for the consequences of their actions and not to endanger the survival of humanity on the planet and also of all life. With this in mind, it should also play a part in shaping their moral character.

This study explores the capabilities of large language models to replicate the behavior of individuals with underdeveloped cognitive and language skills. Specifically, we investigate whether these models can simulate child-like language and cognitive development while solving false-belief tasks, namely, change-of-location and unexpected-content tasks. GPT-3.5-turbo and GPT-4 models by OpenAI were prompted to simulate children (N = 1296) aged one to six years. This simulation was instantiated through three types of prompts: plain zero-shot, chain-of-thoughts, and primed-by-corpus. We evaluated the correctness of responses to assess the models' capacity to mimic the cognitive skills of the simulated children. Both models displayed a pattern of increasing correctness in their responses and rising language complexity. That is in correspondence with a gradual enhancement in linguistic and cognitive abilities during child development, which is described in the vast body of research literature on child development. GPT-4 generally exhibited a closer alignment with the developmental curve observed in 'real' children. However, it displayed hyper-accuracy under certain conditions, notably in the primed-by-corpus prompt type. Task type, prompt type, and the choice of language model influenced developmental patterns, while temperature and the gender of the simulated parent and child did not consistently impact results. We conducted analyses of linguistic complexity, examining utterance length and Kolmogorov complexity. These analyses revealed a gradual increase in linguistic complexity corresponding to the age of the simulated children, regardless of other variables. These findings show that the language models are capable of downplaying their abilities to achieve a faithful simulation of prompted personas.

As socio-natural phenomena, wildfires are exacerbated by climate change and socioeconomic dynamics. However, the role of socioeconomic uncertainty in shaping future wildfire risk and management remains largely neglected. Building on the notion that risk emerges at the intersection of hazard, exposure and vulnerability, we conduct an integrative literature review to identify the most significant socioeconomic drivers of wildfire risk in the European geographical and institutional context and bring this together with the Shared Socioeconomic Pathways (SSP) perspectives on plausible socioeconomic dynamics. To our knowledge, this is the first study to bridge the gap between wildfire research and socioeconomic scenarios to establish a conceptual understanding of future wildfire risk. The resulting wildfire risk scenario space has two main applications: (i) it acts as a qualitative navigator for factoring socioeconomic uncertainty in model-based wildfire risk assessments, and (ii) it sets the boundary conditions for evaluating the feasibility of management strategies. Sustainable land use practices and profitable agricultural value chains can reduce future wildfire risk (e.g. SSP1), whereas land degradation (e.g. SSP4), and socioeconomic disparities (e.g. SSP3) may increase it. As a result, challenges to future wildfire risk management differ significantly across scenarios, leading to paradoxical situations. In scenarios where vulnerability reduction has significant potential to lower risk, socioeconomic challenges reduce the feasibility of implementing the necessary measures to achieve risk reduction. Similar dilemmas may arise in the context of hazard and exposure. By considering multiple plausible futures, this paper emphasizes the importance of accounting for socioeconomic dynamics in shaping wildfire risk and keeping the design of risk management strategies open and flexible in the face of changing circumstances.

Background. Hydrolysed collagen supplements are reported to fight the signs of aging and improve skin appearance, but more authoritative clinical evidence is needed to support efficacy. Aim. This randomised, double-blind, placebo-controlled study evaluated the efficacy of a supplement containing hydrolysed collagen and vitamin C (Absolute Collagen, AC) on biophysical parameters and visible signs of aging for skin, scalp, and hair, when taken daily or every 48 hours. Methods. We measured dermal collagen using confocal microscopy and high-resolution ultrasound. Hydration, elasticity, wrinkles, and clinical trichoscopy were measured in parallel to expert visual grading. Efficacy measures were recorded at baseline, week 6, and week 12. Results. Following 12 weeks daily use of the AC supplement, using confocal microscopy, we observed a significant 44.6% decrease in fragmentation vs. placebo (p

Candida albicans (C. albicans) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by the epithelium. When the epithelial tolerance breaks down, due to C. albicans overgrowth and hyphae formation, the generated inflammatory response and cell damage lead to vulvovaginal candidiasis (VVC) symptoms. Here, we focused on the induction of mitochondrial reactive oxygen species (mtROS) in vaginal epithelial cells after C. albicans infection and the involvement of fungal burden, morphogenesis and candidalysin (CL) production in such induction. Bioluminescent (BLI) C. albicans, C. albicans PCA-2 and C. albicans 529L strains were employed in an in vitro infection model including reconstituted vaginal epithelium cells (RVE), produced starting from A-431 cell line. The production of mtROS was kinetically measured by using MitoSOX™ Red probe. The potency of C. albicans to induced cell damage to RVE and C. albicans proliferation have also been evaluated. C. albicans induces a rapid mtROS release from vaginal epithelial cells, in parallel with an increase of the fungal load and hyphal formation. Under the same experimental conditions, the 529L C. albicans strain, known to be defective in CL production, induced a minor mtROS release showing the key role of CL in causing epithelial mithocondrial activation. C. albicans PCA-2, unable to form hyphae, induced comparable but slower mtROS production as compared to BLI C. albicans yeasts. By reducing mtROS through a ROS scavenger, an increased fungal burden was observed during RVE infection but not in fungal cultures grown on abiotic surface. Collectively, we conclude that CL, more than fungal load and hyphae formation, seems to play a key role in the rapid activation of mtROS by epithelial cells and in the induction of cell-damage and that mtROS are key elements in the vaginal epithelial cells response to C. albicans.

Antecedentes: Las conductas suicidas en adolescentes son un problema de salud pública que va en aumento. Conocer sus factores de riesgo es clave para reducirlas. Objetivo: Identificar la relación entre dos conductas suicidas (ideación e intento) y ocho problemas de salud mental (PSM) en adolescentes mexicanos. Material y métodos: Mediante una encuesta en línea a adolescentes escolarizados de 20 estados, se tamizó la siguiente información: sintomatología de seis PSM (problemas afectivos/ depresión, problemas conductuales, problemas somáticos, problemas de inatención e hiperactividad, problemas oposicionistas desafianes y problemas de ansiedad) y conducta suicida (ideación e intentos de suicidio). Se analizaron frecuencias y porcentajes y se indagó asociación mediante regresión logística binaria. Resultados: Completaron la encuesta 6766 adolescentes entre 11 y 19 años (16.38 ± 1.33), 61.02 % del sexo femenino. El 10 % reportó conducta suicida y entre 3 y 5 %, PSM. Los factores predictivos (χ2 (8) =387.13, p < 0.001) de la conducta suicida fueron problemas afectivos/depresión, problemas conductuales, problemas somáticos, problemas oposicionistas desafiantes y problemas de ansiedad. Conclusión: Cinco problemas de salud mental incrementaron el riesgo de reportar conductas suicidas.

Influenza A virus (IAV) can cause severe respiratory infection leading to significant global morbidity and mortality through seasonal epidemics. Likewise, the constantly increasing number of cancer diseases is a growing problem. Nevertheless, the understanding of the mutual interactions of the immune responses between cancer and infection is still very vague. Therefore, it is important to understand the immunological cross talk between cancer and IAV infection. In several preclinical mouse models of cancer, including melanoma and colorectal cancer, we observed that IAV infection in the lung significantly decreased the tumour burden. Concomitantly, tumour-specific CD8+ T-cells are strongly activated upon infection, both in the tumour tissue and in the lung. CD8+ T-cell depletion during infection reverses the reduced tumour growth. Interestingly, IAV infection orchestrated the migration of tumour-specific CD8+ T-cells from the tumour into the infected lung. Blocking the migration of CD8+ T-cells prevented the anti-tumoural effect. Thus, our findings show that viral respiratory infection has significant impact on the anti-tumour CD8+ T-cell response, which will significantly improve our understanding of the immunological cross talk between cancer and infection.

The demand for lithium-ion batteries (LIBs) has dramatically increased in recent years due to their application in various electronic devices and electric vehicles (EVs). Great amount of LIB waste is generated, most of which ends up in landfills. LIB wastes contain substantial amounts of critical metals (such as Li, Co, Ni, Mn, and Cu) and can therefore serve as valuable secondary sources of these metals. Metal recovery from the black mass (shredded spent LIBs) can be achieved via bioleaching, a microbiology-based technology that is considered to be environmentally friendly, due to its lower costs and energy consumption compared to conventional pyrometallurgy or hydrometallurgy. However, the growth and metabolism of bioleaching microorganisms can be inhibited by dissolved metals. In this study, the indigenous acidophilic chemolithotrophs in a sediment from a highly acidic and metal-contaminated mine pit lake were enriched in a selective medium containing iron, sulfur, or both electron donors. The enriched culture with the highest growth and oxidation rate and the lowest microbial diversity (dominated by Acidithiobacillus and Alicyclobacillus spp. utilizing both electron donors) was then gradually adapted to increasing concentrations of Li+, Co2+, Ni2+, Mn2+, and Cu2+. Finally, up to 100% recovery rates of Li, Co, Ni, Mn, and Al were achieved via two-step bioleaching using the adapted culture, resulting in more effective metal extraction compared to bioleaching with a non-adapted culture and abiotic control.

Tight control of beta cell stimulus-secretion coupling is crucial for maintaining homeostasis of energy-rich nutrients. While glucose serves as a primary regulator of this process, incretins augment beta cell function, partly by enhancing cytosolic [Ca2+] dynamics. However, the details of how precisely they affect beta cell recruitment during activation, their active time, and functional connectivity during plateau activity, and how they influence beta cell deactivation remain to be described. Performing functional multicellular Ca2+ imaging in acute mouse pancreas tissue slices enabled us to systematically assess the effects of the GLP-1 receptor agonist exendin-4 (Ex-4) simultaneously in many coupled beta cells with high resolution. In otherwise substimulatory glucose, Ex-4 was able to recruit approximately a quarter of beta cells into an active state. Costimulation with Ex-4 and stimulatory glucose shortened the activation delays and accelerated beta cell activation dynamics. More specifically, active time increased faster, and the time required to reach half-maximal activation was effectively halved in the presence of Ex-4. Moreover, the active time and regularity of [Ca2+]IC oscillations increased, especially during the first part of beta cell response. In contrast, subsequent addition of Ex-4 to already active cells did not significantly enhance beta cell activity. Network analyses further confirmed increased connectivity during activation and activity in the presence of Ex-4, with hub cell roles remaining rather stable in both control experiments and experiments with Ex-4. Interestingly, Ex-4 demonstrated a biphasic effect on deactivation, slightly prolonging beta cell activity at physiological concentrations and shortening deactivation delays at supraphysiological concentrations. In sum, costimulation by Ex-4 and glucose increases [Ca2+]IC during beta cell activation and activity, indicating that the effect of incretins may, to an important extent, be explained by enhanced [Ca2+]IC signals. During deactivation, previous incretin stimulation does not critically prolong cellular activity, which corroborates their low risk of hypoglycemia.

This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A β-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology.

Glyphosate, a globally prevalent herbicide known for its selective inhibition of the shikimate pathway in plants, is now implicated in physiological effects on humans and animals, probably due to its impacts in their gut microbiomes which possess the shikimate pathway. In this study, we investigate the effects of environmentally relevant concentrations of glyphosate on the gut microbiota, neurotransmitter levels, and anxiety in zebrafish. Our findings demonstrate that glyphosate exposure leads to dysbiosis in the zebrafish gut, alterations in central and peripheral serotonin levels, increased dopamine levels in the brain, and notable changes in anxiety and social behavior. While the dysbiosis can be attributed to glyphosate's antimicrobial properties, the observed effects on neurotransmitter levels leading to the reported induction of oxidative stress in the brain indicate a novel and significant mode of action for glyphosate, namely the impairment of the microbiome-gut-axis. While further investigations are necessary to determine the relevance of this mechanism in humans, our findings shed light on the potential explanation for the contradictory reports on the safety of glyphosate for consumers.

The aim of this article is to describe current Swedish legalisation, clinical practice and future perspectives on the medical ethical decision “Do-Not-Attempt-Cardio-Pulmonary-Resuscitation” (DNACPR) in relation to prevent futile resuscitation of in-hospital cardiac arrests. Sweden has about 2200 in-hospital cardiac arrests yearly, with an overall 30-day survival ratio of 35%. This population is highly selected, although the frequency of DNACPR orders for hospitalized patients is unknown, resuscitation is initiated in only 6–13% of patients dying in Swedish hospitals.According to Swedish law and although shared decision making is sought, the physician is the ultimate decision-maker and consultation with the patient, her relatives and another licenced health care practitioner is mandatory. According to studies, these consultations is documented in only about 10% of the decisions. Clinicians lack tools to assess risk of IHCA, tools to predict outcome and we are not good at guessing patients own will.Future directives for clinical practice need to address difficulties for physicians in making decisions as well as the timing of decisions.We conclude that the principles in Swedish law needs to be fulfilled by a more systematic approach to documentation and planning of meetings between patients, relatives and colleagues.

New concepts are constantly being borrowed across languages. The influence of one language on another can occur on all linguistic levels, with lexis being the most sensitive. Croatian has become most receptive to borrowing from English, and the influence of English on Croatian has been documented in different functional styles. The prestigious status of English, which reduces the likelihood that a borrowed element will adapt to the rules of the recipient language, is one of the reasons why English has become an inexhaustible source of new words for Croatian learners. The aim of the present study is to investigate the use of adapted forms of English loanwords in Croatian, with particular attention to the type and degree of their adaptation. Due to the differences between the phonemic systems of the two languages, it was expected that the Croatian learners would show diversity in their responses regarding loanword adaptation. A translation task with the 392 most frequently used unadapted English loanwords in Croatian was given to 116 undergraduate students at the Faculty of Maritime Studies. The data showed that the participants preferred the unadapted forms to the adapted forms of English. They were also more inclined to orthographically adapt a loanword, than to adapt it both orthographically and morphologically. The differences observed in orthographic adaptation reflect the underlying differences in the phonemic systems of the two languages. Overall, the results suggest that the unadapted forms of English words have become established in Croatian and are a preferred lexical choice among younger L1 speakers of Croatian.

La descripción de la entonación en la costa mexicana es hasta ahora un área de estudio poco explorada; por tanto, su descripción representa una oportunidad para reconocer la diversidad en la variación geoprosódica de México. En este artículo se presentan los resultados del estudio de la entonación en los enunciados declarativos e interrogativos (absolutos y pronominales) en el español de Tonalá, ciudad perteneciente a la región istmo-costa del estado de Chiapas (México) y tiene como objetivo el registro de las diferencias y semejanzas entre la entonación de dicho municipio y la documentada en otras ciudades del país para reconocer la posible existencia de un español costeño mexicano. En este estudio se consideró como base teórica el modelo autosegmental (Pierrehumbert, 1980; Ladd, 1996; Hualde, 2003) y la notación Sp_ToBI (Hualde y Prieto, 2015). Los resultados sugieren que no existen mayores diferencias entre el español hablado en las costas de Tonalá en comparación con otras variedades mexicanas hasta ahora descritas. Sin embargo, se reconocen particularidades entonativas en los enunciados interrogativos, lo que valida la propuesta de que los rasgos prosódicos característicos de cada variante dialectal del español se reflejan, principalmente, en este tipo de enunciados.

Il settimo centenario della morte di Dante (1321-2021) è stata una propizia occasione per rinnovare il rapporto con il Poeta, con la sua opera sempre complessa e sempre ricca di suggestioni, con gli ‘oggetti’ che la tramandano – dai manoscritti agli album d’artista, per rimanere in un ambito circoscritto. Ogni epoca ha avuto il proprio Dante, talora anche più di uno, e la contemporaneità non poteva sottrarsi a tale confronto/incontro. Per l’occasione, la Biblioteca Apostolica Vaticana ha perciò curato una mostra online, Viaggiare con Dante (https://www.vaticanlibrary.va/it/viaggiare-con-dante.html), promossa dal Comitato scientifico-organizzativo dantesco del Pontificio Consiglio della Cultura e dal “Cortile dei Gentili”; in essa si espongono soprattutto manoscritti (commentati dalle annotazioni in IIIF), ma anche stampati, incisioni e medaglie, patrimonio dell’istituzione. Indagare una materia di così sfaccettata stratificazione attraverso tecnologie all’avanguardia ha comportato un mutamento del punto di osservazione, rivelando inedite possibilità di ricerca.

Bone metastases cause pain and impair quality of life, and they can lead to serious complications that require immediate treatment. Urgent surgical treatment followed by postoperative radiotherapy should be considered in bone metastases with an impending or existing pathologic fracture or spinal cord compression. Patients who are unable or unwilling to undergo surgery should be referred for urgent radiotherapy. Patients with painful bone metastases without an impending or existing pathologic fracture and no spinal cord compression, regardless of the size of the metastatic lesion, are treated pharmacologically first, complemented by palliative irradiation. In palliative radiation, low total doses are prescribed and delivered in a single fraction or in short fractionation regimens. Patients with insufficient pain relief or pain relapse after initial radiation can be safely reirradiated. We conducted a retrospective review of palliative bone irradiations between 2018 – 2021 at the Institute of Oncology Ljubjana. Annually, we treat 800 bone metastases and we are seeing a decline in the number of irradiations. The most common fractionation is 5 x 4 Gy, with only 10% of patients receiving single-dose treatment. Palliative irradiation for painful bone metastases is effective, inexpensive, and safe. It is critical to select patients who will benefit from radiation therapy and present them in a multidisciplinary team meeting. Radiation treatment can be made easier to use by simplifying the procedure for the patient and prescribing the dose in one fraction.

Předložený článek popisuje teorii vibrací, jak ji můžeme nalézt v díle Josepha Priestleyho. Priestley byl anglický polyhistor 18. století, který se stal známý především díky svým kontroverzním politickým a teologickým názorům, ale i díky proklamování materialismu a determinismu. V tomto článku se zaměříme na jednotlivé oblasti jeho teorie vnímání a poznání. Popíšeme, jak vznikají jednotlivé počitky a ideje a jak je možné na základě této teorie vysvětlit i složitější operace mysli – vznik abstraktních idejí, myšlení, paměti a dalších duševních schopností. Taktéž se zaměříme na otázku, jak je možné propojit ideje s pohyby těla a lidskou vůlí. Na konci se budeme zabývat otázkou, zda má taková teorie místo i v soudobém bádání.

This study investigates the experimental conditions required for magnetic resonance imaging (MRI) of thermally polarized hydrocarbon gas, focusing on ethane. The nuclear magnetic resonance (NMR) spectra and relaxation properties of ethane were analysed at different pressures in the range from 1.5 to 6 bar at 7 T using 1H NMR spectroscopy. The spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) were measured, and their dependence on the pressure was determined, showing that both relaxation times increase with pressure. Using the estimated relaxation times, we adjusted parameters for imaging of static ethane using rapid acquisition with relaxation enhancement (RARE) and fast low-angle shot (FLASH). The signal-to-noise ratio (SNR) of ethane images was evaluated and compared to the calculation for the given range of pressures. Then, we imaged flowing gas using a 2D velocity-encoded pulse sequence, which is usually used for liquid flow studies. The MRI-measured flow rates are compared to those pre-set with a pump, showing good agreement in the slow flow range. Overall, the results provide insights into the feasibility of 1H MRI for imaging and flow measurements of thermally polarized ethane.

Purpose Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. Materials and Methods Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas Results All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. Conclusion Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

Objective To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR). Methods A comprehensive search in PubMed, Embase, Web of Science, and Scopus was performed. Prospective or retrospective studies reporting on MFPR from triplet or higher-order to twin compared to ongoing (i.e., non-reduced) triplets and/or twins were included. A meta-analysis of the primary outcome HDP was carried out using a random-effects model. Subgroup analyses of gestational hypertension (GH) and preeclampsia (PE) were performed. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Results Thirty studies with a total of 9,811 women were included. MFPR from triplet to twin was associated with a lower risk for HDP compared to ongoing triplets (OR 0.55, 95% CI, 0.37–0.83; p = 0.004). In a subgroup analysis, the decreased risk of HDP was driven by GH, and PE was no longer significant (OR 0.34, 95% CI, 0.17–0.70; p = 0.004 and OR 0.64, 95% CI, 0.38–1.09; p = 0.10, respectively). HDP was also significantly lower after MFPR from all higher-order (including triplets) to twin compared to ongoing triplets (OR 0.55, 95% CI, 0.38–0.79; p = 0.001). In a subgroup analysis, the decreased risk of HDP was driven by PE, and GH was no longer significant (OR 0.55, 95% CI 0.32–0.92; p = 0.02 and OR 0.55, 95% CI 0.28–1.06; p = 0.08, respectively). No significant differences in HDP were found in MFPR from triplet or higher-order to twin versus ongoing twins. Conclusions MFPR in women with triplet and higher-order multifetal pregnancies decreases the risk of HDP. Twelve women should undergo MFPR to prevent one event of HDP. These data can be used in the decision-making process of MFPR, in which the individual risk factors of HDP can be taken into account.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Abstract The mechanisms of communication between the brain and the immune cells are still largely unclear. Here, we characterize the populations of resident natural killer (NK) cells and innate lymphoid cells (ILC) 1 in the meningeal dura layer of adult mice. We describe that ILC1/NK cell-derived interferon-γ and acetylcholine can contribute to the modulation of brain homeostatic functions, shaping synaptic neuronal transmission and neurotransmitter levels with effects on mice behavior. In detail, the interferon-γ plays a role in the formation of non-spatial memory, tuning the frequency of GABAergic neurotransmission on cortical pyramidal neurons, while the acetylcholine is a mediator involved in the modulation of brain circuitries that regulate anxiety-like behavior. These findings disclose mechanisms of immune-to-brain communication that modulate brain functions under physiological conditions.

Abstract The hippocampus and entorhinal cortex are deeply involved in learning and memory. However, little is known how ongoing events are processed in the hippocampal-entorhinal circuit. By recording from head-fixed rats during action-reward learning, here we show that the action and reward events are represented differently in the hippocampal CA1 region and lateral entorhinal cortex (LEC). Although diverse task-related activities developed after learning in both CA1 and LEC, phasic activities related to action and reward events differed in the timing of behavioral event representation. CA1 represented action and reward events almost instantaneously, whereas the superficial and deep layers of the LEC showed a delayed representation of the same events. Interestingly, we also found that ramping activity towards spontaneous action was correlated with waiting time in both regions and exceeded that in the motor cortex. Such functional activities observed in the entorhinal-hippocampal circuits may play a crucial role for animals in utilizing ongoing information to dynamically optimize their behaviors.

Abstract With the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment strategies. Here, we study 1084 eQTLs affecting the TIME found through analysis of The Cancer Genome Atlas and literature curation. These TIME eQTLs are enriched in areas of active transcription, and associate with gene expression in specific immune cell subsets, such as macrophages and dendritic cells. Polygenic score models built with TIME eQTLs reproducibly stratify cancer risk, survival and immune checkpoint blockade (ICB) response across independent cohorts. To assess whether an eQTL-informed approach could reveal potential cancer immunotherapy targets, we inhibit CTSS, a gene implicated by cancer risk and ICB response-associated polygenic models; CTSS inhibition results in slowed tumor growth and extended survival in vivo. These results validate the potential of integrating germline variation and TIME characteristics for uncovering potential targets for immunotherapy.

Este artículo presenta un marco con una triple dimensión (material, educativa y psicoemocional) a partir del cual se analizan las características, procesos y resultados de la educación remota de emergencia implementada por las universidades presenciales durante la pandemia por COVID-19. A tal fin, se diseñaron dos cuestionarios ad hoc que se aplicaron en los meses de abril-mayo a una muestra de 220 docentes y 548 estudiantes en una universidad española. Los resultados más significativos evidencian una desigualdad digital en términos de tipo de equipamiento tecnológico y calidad de la conectividad entre los estudiantes. El diseño de la educación remota ha consistido en la traslación del modelo de enseñanza presencial al espacio virtual. Docentes y estudiantes experimentan una sobrecarga de trabajo que puede ayudar a explicar la alta afección de estrés de ambos. El estudio concluye con propuestas para mejorar la calidad y la eficacia de la enseñanza a distancia ante eventuales crisis.

Abstract Background Chicks of precocial birds hatch well-developed and can search actively for food but their homeothermy develops gradually during growth. This makes them dependent on heat provided by parents (“brooding”), which is then traded off against other activities, mainly foraging. Although brooding has been documented in many precocial birds, little is known about the differences in the amount and efficiency of brooding care, brooding diel rhythmicity, and impact on the chick’s growth, particularly between species living in different climatic conditions. Results We used multisensory dataloggers to evaluate brooding patterns in two congeneric species inhabiting contrasting climate zones: temperate Northern lapwing (Vanellus vanellus) and desert Red-wattled lapwing (Vanellus indicus). In accordance with our expectation, the adult desert lapwings brooded the chicks slightly less compared to the adult temperate lapwings. However, the desert lapwings brooded their chicks in higher ambient temperatures and less efficiently (i.e. they could not reach the same brooding temperature as the temperate lapwings), which are new and hitherto unknown brooding patterns in precocial birds. In both species, night brooding prevailed even during warm nights, suggesting a general brooding rule among birds. Although the high rates of brooding can reduce the time spent by foraging, we found no negative effect of the high brooding rate on the growth rate in either species. Conclusions Our data suggest that the chicks of species breeding in colder climates may reduce their thermal demands, while their parents may increase the efficiency of parental brooding care. More research is however needed to confirm this as a rule across species.

It is established that topological spin textures are a rich source for emergent physical properties; it remains a major challenge, however, to unravel their local structure and topological connections. Here, the authors apply X-ray vector magnetic tomography to gain insight into the magnetic structure near Bloch points at permalloy microstructures and identify several topological monopoles and dipoles within the domain wall core.

Abstract Background This retrospective cohort study aimed to compare treatment results between bilateral extraction of upper second molars (M2) and first premolars (P1) in terms of treatment timing, cephalometry, upper third molar alignment and relapse in the long-term. Methods Fifty-three consecutively treated Caucasian patients with a brachyfacial pattern, skeletal class I and dental class II requiring extraction in the maxilla due to crowding were retrospectively divided into group I (M2 extracted; N = 31) and II (P1 extracted; N = 22). Fixed appliances were inserted after extraction and after distalisation of the first molars in group I. Post-treatment lateral cephalograms were digitally analysed and compared between groups. Six to seven years later relapse and success of upper third molar alignment were clinically evaluated as well as orthodontic treatment duration, pre-treatment age and gender recorded. Results After debonding patients with second molar extraction showed significantly smaller values for the Wits-appraisal, but higher values for index and facial axis. Extracting first premolars caused significantly more retroinclination/−position of anterior teeth and an increased profile concavity, more relapse and less successful alignment of upper third molars. Orthodontic treatment duration, pre-treatment age and gender were not significantly different between groups. Conclusions Bilateral extraction of upper first premolars or second molars may solve dental crowding in skeletal class I dental class II patients with a brachyfacial growth pattern. Upper second molar extraction seems to affect maxillary third molar alignment, long-term stability and dental and soft-tissue cephalometric parameters positively, but no intervention proved to be clearly superior.

This study aimed to investigate the effects of dietary supplementation with modified-hen-egg-yolk on plasma lipids and lipoprotein profiles in rats. During the four-week-experiment, 64 Wistar rats were divided into four groups of 16 (eight of both sexes), and fed commercial rat food (group C); food containing 70% commercial rat mixture and 30% freshly cooked egg yolk originating from laying hen eggs fed with 3% fish oil (group F); 3% palm olein (group P), or 3% lard (group L). The cooked egg yolk in the rat diet affected the concentrations of plasma total and LDL-cholesterol in males of the P and L groups. Cholesterol and total fat in the diet did not have a hypercholesterolemic effect on their own, but when in combination with fatty acid composition, they could contribute to an increase in plasma total and LDL cholesterol concentrations in rats. HDL-cholesterol was the most resilient plasma lipoprotein of rats to dietary treatments in our experiment. Compared to the control group, the addition of hen egg yolk to the rat diet regardless of its quality, adversely affected the values of HDL-C/TC and HDL-C/LDL-C in both males and females.

Due to the falling water level in the Aral Sea and Muynak Lake, the content of salts dissolved in the water has gradually increased, and toxic elements have been deposited at the lake’s bottom and subsequently washed into the Aral region by the river. Bacteria, archaea and fungi are crucial for the cycling of several important inorganic nutrients in soils. From 15 genera and 31 species of recovered microscopic filamentous fungi, a big group was melanized, of which most of them were also phytopathogenic. The second group consisted of keratinophilic species. Isolated bacteria mainly included members of the genera Arthrobacter, Bacillus, Massilia, Rhodococcus and Nocardiopsis. High-throughput sequencing analysis permitted a better view of the mycobiome and prokaryotic communities (comprising archaea). The cultivation and sequencing approaches were shown to be complementary. The aim of the work was to identify soil microorganisms, including the order Halobacteriales, and to discover the differences in species diversity depending on soil salinity and the presence of PTEs in soil.

Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation of the physiological consequences of venom exposure and the assessment of toxicity using animal models. Chicken embryos serve as valuable models for assessing venom toxicity through the chick embryotoxicity screening test (CHEST) and the chick chorioallantoic membrane (CAM) assay, particularly useful for evaluating vascular impacts. C. adamanteus venom application resulted in higher embryotoxicity and morphological abnormalities, such as Siamese twins. The CAM assay demonstrated the hemorrhagic effects of venom, varying with venom type and concentration. The irritant potential of both venom types was classified as slight or moderate depending on their concentration. Additionally, acetylcholinesterase (AChE) activity was performed to receive information about organ toxicity. The results show that both venoms induced changes in the whole embryo, heart, and liver weights, but the C. adamanteus venom was identified as more toxic. Specific venom concentrations affected AChE activity in embryonic tissues. These findings underscore the embryotoxic and vasoactive properties of Crotalus venoms, providing valuable insights into their mechanisms of toxicity and potential applications in biomedicine.

Freshwater ecosystems, particularly rivers and lakes, are under severe pressure due to increasing anthropogenic activities, such as water extraction, flow regulation, pollution, and habitat fragmentation [...]

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work, we have analyzed the influence of age (5–8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4004 analyses for each behavior) in 143 larvae. The results from both behaviors were adjusted to a random-effects linear regression model using generalized least squares (GLSs), including in the model the effect of the three variables, the second-way interactions between them, and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on the age of the larva and the behavioral test.

Non-Saccharomyces yeasts, particularly Metschnikowia pulcherrima, are considered alternatives to SO2 in winemaking, combating specific microorganisms. The sensory profile of the wine is contingent upon the type of yeast, the fermentation conditions, and the concentration and mode of application with Saccharomyces cerevisiae strains (whether pure or used in mixed/sequential co-fermentation). This study assessed the aroma in red wines produced with S. cerevisiae (Sc) and M. pulcherrima (Mp, non-Sc), incorporating variations in the method of addition and the inclusion or exclusion of SO2. The enological parameters of the wines were slightly affected. Volatile compounds were analysed in the wines through gas chromatography–mass spectrometry (GC-MS) at three moments: at the end of malolactic fermentation (MLF) and after 6 and 9 months of bottle ageing. Sequential fermentation of Sc and Mp reduced the concentration of most identified alcohols and acids, which is favourable, as these compounds can yield undesirable aromas at high concentrations. Regardless of the yeast mixture and Mp dose, a majority of the acetate esters and ethyl esters were quantified at concentrations above their perception thresholds, thus enhancing the sensory quality of the wines. Sensory analysis of wines showed generally positive evaluations. Using non-Saccharomyces as an alternative to SO2 improves the aromatic profile of wines.

This study examines gender differences in levels of sexism among university students and evaluates variations in assessing sexist attitudes toward professors. The aim is to analyze potential disparities between men and women regarding ambivalent sexism (both hostile and benevolent) and to determine if these differences influence the evaluation of specific behaviors by teaching faculty. Additionally, the present study seeks to validate the variability hypothesis, asserting that men are over-represented in the extremes of distributions compared to women concerning analyzed sexist attitudes. Eighty university students participated voluntarily and anonymously, completing three questionnaires on ambivalent sexism, neosexism, and the assessment of sexist behaviors by their instructors. Consistent with prior research, the results reveal higher levels of sexism among men in this context. Despite these differences, both men and women align in evaluating specific behaviors in teaching faculty, irrespective of their individual levels of sexism. Finally, the data presented support the variability hypothesis, indicating greater variability in sexist attitudes among men than women. These findings suggest that general attitudes assessed in most questionnaires might not be representative of the behaviors and attitudes that people display in real specific situations. This could change how future research and interventions approach these issues.

In recent years, the search for new compounds with antibacterial activity has drastically increased due to the spread of antibiotic-resistant microorganisms. In this study, we analyzed Cell-Free Supernatant (CFS) from Bacillus siamensis, assessing its potential antimicrobial activity against some of the main pathogenic microorganisms of human interest. To achieve this goal, we exploited the natural antagonism of skin-colonizing bacteria and their ability to produce compounds with antimicrobial activity. Biochemical and molecular methods were used to identify 247 strains isolated from the skin. Among these, we found that CFS from a strain of Bacillus siamensis (that we named CPAY1) showed significant antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, and Candida spp. In this study, we gathered information on CFS’s antimicrobial activity and on its sensitivity to chemical–physical parameters. Time–kill studies were performed; anti-biofilm activity, antibiotic resistance, and plasmid presence were also investigated. The antimicrobial compounds included in the CFS showed resistance to the proteolytic enzymes and were heat stable. The production of antimicrobial compounds started after 4 h of culture (20 AU/mL). CPAY1 CFS showed antimicrobial activity after 7 h of bacteria co-culture. The anti-biofilm activity of the CPAY1 CFS against all the tested strains was also remarkable. B. siamensis CPAY1 did not reveal the presence of a plasmid and showed susceptibility to all the antibiotics tested.

The common bean is an important legume valued for its protein-rich seeds and its ability to fix nitrogen, making it a key element of crop rotation. In conventional agriculture, the emphasis is on uniformity and genetic purity to optimize crop performance and maximize yields. This is due to both the legal obligations to register varieties and the challenges of implementing breeding programs to create genetically diverse varieties. This paper focuses on the factors that influence the occurrence of heterogeneous common bean populations. The main factors contributing to this diversity have been described, including local adaptations, variable weather conditions, different pollinator species, and intricate interactions between genes controlling seed coat colour. We also discuss the benefits of intercropping common beans for organic farming systems, highlighting the improvement in resistance to diseases, and adverse environmental conditions. This paper contributes to a better understanding of common bean seed heterogeneity and the legal obligation to use heterogeneous populations.

Soil water availability during the vine growth cycle can affect yield and grape quality. The objective was to evaluate the effect of soil water holding capacity (AWC) and available soil water (ASW) throughout the growing cycle on the nutritional status, vigor, production, and composition of grapes and wine. The study was conducted in the municipality of Uruñuela in the DOCa Rioja (Spain). The soils of four rainfed vineyard plots were characterized to determine AWC and its impacts on vine, grape, and wine composition. The N, P, and K foliar content, vigor, grape yield, berry weight, and composition of must and wine were analyzed in those vineyard plots during the period 2010–2014. The ASW was simulated in each plot and each year analyzed, considering the soil properties and the weather conditions, after model calibration in one plot in which soil water content was registered. The results showed that AWC influenced ASW along the growing cycle, so vines suffered from water stress in some periods of the vegetative cycle. Plots with higher AWC had higher ASW from fruit set to ripening and lower water stress during this period, which explains the higher N, P, and K foliar content, vigor and grape yield, and lower polyphenol and anthocyanin content in grapes and wines. The period where water availability had the most influence on the quality of the grapes was from veraison to ripening, during which ASW increased berry weight and acidity and decreased anthocyanins and polyphenolic compounds.

Lactic acid bacteria are considered an inexhaustible source of bioactive compounds; indeed, products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that Cell-Free Supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, Lactiplantibacillus (L.) plantarum, Lacticaseibacillus (L.) rhamnosus, and Limosilactobacillus (L.) reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactic acid bacteria on Candida virulence and to the production of metabolites that are able to impair fungal virulence. In the present work, stemming from these data, we deepened our knowledge of CFS from these four lactic acid bacteria by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactic acid bacteria. Interestingly, L. rhamnosus and L. acidophilus showed the most peculiar metabolic profiles. Specifically, after a hierarchical clustering analysis, L. rhamnosus and L. acidophilus showed specific areas of significantly overexpressed metabolites that strongly differed from the same areas in other lactic acid bacteria. From the overexpressed compounds in these areas, inosine from L. rhamnosus returned with the best identification profile. This molecule has been described as having antioxidant, anti-inflammatory, anti-infective, and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity.

We report a novel RPGR missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the RPGR variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated RPGR gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings’ nasal brushing samples. In addition, a missense variant in CEP290 was identified. The concurrent RPGR variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant’s pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the CEP290 gene may be a potential modifier for respiratory symptoms in patients with RPGR mutations.

Background: Occlusal splints and anterior repositioning splints (ARSs) are widely accepted treatments for temporomandibular disorders (TMDs). However, there is uncertainty with regard to the most suitable amount of mandibular repositioning. The aim of this study is to evaluate the clinical and functional effects of the therapeutic position (ThP) established based on the Controlled Mandibular Repositioning (CMR) method. Methods: In this clinical trial, 20 subjects with 37 joints with disc displacement with reduction were recruited. The initial standard functional diagnostic protocol, MRI, and digital condylography were performed, and ThP was calculated with the CMR method. After a 6-month follow-up, the standard diagnostic protocol was repeated. The change in disc position was evaluated by means of MRI after 6 months of CMR therapy. Results: The MRI findings in the parasagittal plane demonstrated that out of the 37 joints presenting disc displacement, 36 discs were successfully repositioned; thus, the condyle–disc–fossa relationship was re-established. Therefore, the success rate of this pilot study was 97.3%. The mean position of the displaced discs was at 10:30 o’clock of the TMJ joint and at 12:00 o’clock after CMR therapy. Conclusions: The ThP determined using the CMR approach reduced all of the anteriorly displaced discs (except one). The CMR method allowed to define an optimum ThP of the mandible thus supporting patients’ effective adaptation to treatment position.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

Background: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. Methods: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. Results: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. Conclusion: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection.

This editorial of the Journal of Awareness-based Systems Change delves into the complex entanglements of our inner and outer worlds. We delve into the nuances of feeling overwhelmed, and fatigued due to our deep, visceral connections with global events. Central to our narrative is the recognition of the intricate web of relationships that underpin all systemic change efforts. Through a lens of decolonialization and Awareness-Based Systems Change, we explore the necessity of reevaluating and transforming these connections. The editorial underscores the urgency of mending and honoring these relationships, emphasizing their role in reshaping our systems. We advocate for a holistic approach that includes affective, relational, and intellectual work, aiming to transcend traditional boundaries and foster a more interconnected and empathetic world. This editorial is a call to action for conscious engagement, inviting readers to participate in collective purpose-shaping and world-making, transforming vulnerabilities into a collective strength for systemic renewal

In March 2023, one hundred and sixty leaders and change-makers from fourteen countries across Latin America participated in a four-day gathering held by the Presencing Institute called the Ecosystem Leadership Program (ELP) in Latin America. A system of scholarship and support was created to ensure the event was inclusive and representative of the region’s diversity. The program is striking as an example of grassroots action taking place at scale. In this dialogue, six members of the holding team engage in a facilitated conversation about what it takes to weave together multiple dimensions of diversity and push the boundaries of inclusion.

Summary: Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of RPS2 K275 abrogate ribosomal delivery to lysosomes without affecting bulk autophagy. We show that the selective recruitment of ubiquitinated ribosomes to autophagosomes is mediated by the p62 receptor. While ribophagy is not required for the establishment of senescence per se, it contributes to senescence-related metabolome alterations and facilitates the senescence-associated secretory phenotype.

Introduction Preterm birth (PTB) is among the leading causes of perinatal and childhood morbidity and mortality. Therefore, accurate identification of pregnant women at high risk of PTB is key to enable obstetric healthcare professionals to apply interventions that improve perinatal and childhood outcomes. Serial transvaginal cervical length measurement is used to screen asymptomatic pregnant women with a history of PTB and identify those at high risk for a recurrent PTB. Cervical length measurement, fetal fibronectin test or a combination of both can be used to identify women at high risk of PTB presenting with symptoms of threatened PTB. The predictive capacity of these methods can be improved. Cervical softening is a precursor of cervical shortening, effacement and dilatation and could be a new marker to identify women a high risk of PTB. However, the predictive value of cervical softening to predict spontaneous PTB still needs to be determined.Methods and analysis This is a single-centre, prospective cohort study, conducted at the Amsterdam University Medical Centers in the Netherlands. Cervical softening will be investigated with a non-invasive CE-marked device called the Pregnolia System. This device has been developed to evaluate consistency of the cervix based on tissue elasticity. Two different cohorts will be investigated. The first cohort includes women with a history of spontaneous PTB