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Background: Current literature suggests that immersive virtual reality (IVR) could be an efficacious therapeutic approach for patients with cardiovascular diseases (CVD) undergoing cardiac rehabilitation program (CRP). However, this has only been affirmed in individual studies and is yet to be confirmed by a systematic review., Objectives: To determine the efficacy of IVR interventions on depression, anxiety, and stress symptoms in patients with CVD., Methods: A meta-analysis was performed in line with PRISMA guidelines following a literature search between inception and June 2024 in PubMed, SCOPUS, WOS, CINAHL and PEDro for retrieving randomized controlled trials (RCTs) that compared the efficacy of IVR versus conventional CRPs on depression, anxiety and stress in patients with CVD. The PEDro scale was used to evaluate the methodological quality of the studies. Pooled effects were calculated using the Cohen's standardized mean difference (SMD) and its 95% confidence interval (95% CI), or mean difference (MD) if studies used the same measure., Results: Eight RCTs, providing data from 510 patients with CVD (63.8±5.4 years, 60% men), were included. The methodological quality was moderate (M=5.1±1 points). A large rehabilitative effect of IVR was found for reducing depression (SMD=-0.54; 95% CI -0.77 to -0.31; p<0.001), anxiety (SMD=-0.43; 95% CI -0.74 to -0.12; p=0.006) and stress (MD=-14.96; 95% CI -20.1 to -9.8; p<0.001). The findings suggest that combine IVR and CRP is the most appropriate approach for reducing depression, anxiety and stress., Conclusion: IVR, especially when combined with a traditional CRP, reduces depression, anxiety and stress in patients with CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To communicate the results and complications in a series of 17 proximal lacrimal pathway obstructions (PLPO) operated by conjunctivo-rhinostomy (CR) with Métaireau tube implantation., Methods: Retrospective descriptive study including 16 patients (17 PLPO) operated with CR between April 2010 and June 2017. Surgeries were performed under general anesthesia. The Métaireau tube implantation, draining into the middle meatus, was carried out through a trans-caruncular osteotomy with a 14G Abbocath catheter under endoscopic control., Results: Twelve women (75%) and four men (25%) were included. The median age was 57 years (range 32-78). The indication for surgery was constant epiphora (Munk 4) due to obstruction less than 8 mm from the punctum. The follow-up time was 28 months (range 2-85). Epiphora improved one month after the intervention (Munk 0.35 ± 1) and at the end of follow-up (Munk 1.50 ± 1.10) compared to baseline values (Munk 4). The most frequent postoperative symptoms were hyperemia (35%), discharge (24%), and tearing (24%). The detected signs were conjunctival folds and papillomas at the proximal end of the tube (35% and 24%, respectively) and tube malposition (18%). One patient developed restrictive strabismus. 41% of the cases required at least one surgery to reposition or remove the tube., Conclusions: CR with Métaireau tube implantation is a therapeutic alternative for PLPO. Despite the good anatomic results, patients should be warned about the potential complications, which are frequent and may require reoperations., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in relation to the present work., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Purpose: Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome that leads to higher morbidity and mortality. We investigated the association between serum C-reactive protein (CRP) and the occurrence of POD in older hip fracture patients, and whether CRP predicted POD better than a clinical model., Methods: Patients aged ≥ 75 years admitted for surgical repair of an acute hip fracture were recruited. We compared serum CRP levels between patients with and without POD., Results: Sixty patients were included, of whom 21 (35%) developed POD. Serum CRP levels were significantly higher in patients who developed delirium (p = 0.011). In a multiple regression model including clinical variables and CRP, cognitive impairment (p = 0.003) and infection (p = 0.001) were the best predictors of POD., Conclusions: Although higher levels of serum CRP were significantly associated with POD in older hip fracture patients, pre-existing cognitive impairment and infections were the most important risk factors for POD., Competing Interests: Declarations. Conflict of interest: The authors declare they have no conflict of interest. Ethical approval: Ethical approval was agreed by the Ethical Comittee of the Institution. Informed consent: Informed consent was obtained from all patients prior to all surgical procedures., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women., Methods: This retrospective case-control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n  = 40) and late (≥34 weeks, n  = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls ( n  = 80) and were further stratified into early ( n  = 25) and late ( n  = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay., Results: 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924-2926) pg/mL vs. 630 (448-4002) pg/mL, p  = .026, and late preeclampsia: 1833 (1441-5534) pg/mL vs. 910 (526-6178) pg/mL, p  = .021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070-3188) pg/mL vs. without MVM: 888 (812-1781) pg/mL, p  = .03; and with MVM vs. control: 630 (448-4002) pg/mL, p  = .04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy ( p  = .3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392-3135) pg/mL vs. control: 910 (526-6178), p  = .045; and without MVM: 2023 (1578-8936) pg/mL vs. control, p  = .01]., Conclusions: MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.

Tomato sensory analysis typically involves assessing different fruits, and the inherent intra- and inter-fruit variability poses experimental challenges. To address this, blending emerges as a sampling protocol to minimize panelist experimental error. This study delves into intra-(locule/pericarp) and inter-fruit heterogeneity, examining the efficacy of blended samples in assessing sweetness and acidity. Results reveal a higher acidity (22.2%) and sweetness perception (10.3%) in locular tissue, influenced by elevated titratable acids (TA) and soluble solids (TSS). The observed locular-to-fruit weight ratios (6-31%) might impact overall taste intensity. Fruit-to-fruit variation was high among the 16 varieties studied for TA, TSS, and dry matter. The use of blending to construct an "average" sample, increased sweetness (23%) and acidity perception (17%) without affecting sample ordering. Our results underscore the need to integrate locular relative weight into tomato phenotyping protocols and highlight the potential of blended samples in sensory analysis of traits related to the non-volatile fraction., Competing Interests: DECLARATION OF CONFLICTING INTERESTSThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The pursuit of automated methods to assess the extent of resection (EOR) in glioblastomas is challenging, requiring precise measurement of residual tumor volume. Many algorithms focus on preoperative scans, making them unsuitable for postoperative studies. Our objective was to develop a deep learning-based model for postoperative segmentation using magnetic resonance imaging (MRI). We also compared our model's performance with other available algorithms., Methods: To develop the segmentation model, a training cohort from 3 research institutions and 3 public databases was used. Multiparametric MRI scans with ground truth labels for contrast-enhancing tumor (ET), edema, and surgical cavity, served as training data. The models were trained using MONAI and nnU-Net frameworks. Comparisons were made with currently available segmentation models using an external cohort from a research institution and a public database. Additionally, the model's ability to classify EOR was evaluated using the RANO-Resect classification system. To further validate our best-trained model, an additional independent cohort was used., Results: The study included 586 scans: 395 for model training, 52 for model comparison, and 139 scans for independent validation. The nnU-Net framework produced the best model with median Dice scores of 0.81 for contrast ET, 0.77 for edema, and 0.81 for surgical cavities. Our best-trained model classified patients into maximal and submaximal resection categories with 96% accuracy in the model comparison dataset and 84% in the independent validation cohort., Conclusions: Our nnU-Net-based model outperformed other algorithms in both segmentation and EOR classification tasks, providing a freely accessible tool with promising clinical applicability., Competing Interests: All the authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

To overcome the toxic nature of organic solvents, scientific interest in the use of green solvents, particularly natural deep eutectic solvents (NADES), has increased over the past decade, leading to new applications in the food, nutraceutical, pharmaceutical, and cosmetic industries. Understanding the physicochemical properties and molecular interactions of NADES is essential for uncovering new potential applications in these fields. In this study, several lactic and citric acid-based NADES, as well as chloride choline- and urea-based NADES, were evaluated for their physicochemical properties, including density, pH, viscosity, conductivity, and refractive index. Additionally, nuclear magnetic resonance (NMR), and in particular nuclear Overhauser enhancement spectroscopy (NOESY), was employed to investigate the intermolecular interactions between the NADES components to confirm the formation of the eutectic mixture. The extraction efficiency of the confirmed NADES was tested for extracting polyphenols as a proof of concept to highlight their relationship with the measured properties. Lactic and choline chloride-based NADES provided the highest extraction yields. These results were also compared with the predicted extraction capabilities of each NADES provided by the COSMO-RS software., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Physical function deficits and frailty are commonly reported in people experiencing homelessness and addiction. Typically, geriatric, or general physical performance measures are employed to evaluate these constructs., Objectives and Setting: We aimed to investigate the feasibility of a broad test battery to evaluate physical functioning and frailty in a non-geriatric community-based population of people experiencing homelessness and addiction., Design and Methods: Physical function and the presence of frailty was evaluated using combined data from two linked low-threshold exercise pre-post intervention studies (LEAP-I and II)., Participants: Seventy-four participants attending an open-access day-service centre (18 to 65 years) were evaluated. Participants with acute confusion or behavioural issues, or major medical conditions precluding safe participation were excluded., Intervention: A broad test battery was performed which evaluated physical functioning and frailty., Main Outcome Measures: Outcome measures included were the Short Physical Performance Battery, Single Leg Stance, Chair Stand Test, 10mWT and 2 Minute Walk Tests, limb circumference, dynamometry, Clinical Frailty Scale, SHARE-Frailty Instrument, Numerical Pain Rating Scale and Short Form-12., Results: Test completion was 100% for all outcomes except pain rating (81% and 79% for LEAP-I and II, respectively), and balance and walking tests (95% and 93% in LEAP-II). A ceiling effect was detected for the Short Physical Performance Battery., Conclusion: High feasibility of the test batteries was demonstrated. An optimised test battery was proposed based on findings. This has important implications for clinicians working in inclusion health settings., Clinical Trial Registration Number: Clinical Trials.gov: NCT05700305. CONTRIBUTION OF THE PAPER., Competing Interests: Conflict of Interest The authors have no conflicting interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Hospital-associated deconditioning is a broad term, which refers non-specifically to declines in any function of the body secondary to hospitalisation. Older people, particularly those living with frailty, are known to be at greatest risk. It has historically been most commonly used as a term to describe declines in muscle mass and function (i.e. acute sarcopenia). However, declines in physical function do not occur in isolation, and it is recognised that cognitive deconditioning (defined by delayed mental processing as part of a spectrum with fulminant delirium at one end) is commonly encountered by patients in hospital. Whilst the term 'deconditioning' is descriptive, it perhaps leads to under-emphasis on the inherent organ dysfunction that is associated, and also implies some ease of reversibility. Whilst deconditioning may be reversible with early intervention strategies, the long-term effects can be devastating. In this article, we summarise the most recent research on this topic including new promising interventions and describe our recommendations for implementation of tools such as the Frailty Care Bundle., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To evaluate health-related quality of life perceived by patients with the most prevalent immune-mediated inflammatory diseases in Spain: inflammatory bowel disease (IBD), psoriasis (Ps), psoriatic arthritis (AP), rheumatoid arthritis (RA), and spondyloarthropathies (SpAs), and to determine the factors that influence patient quality of life., Methods: The SACVINFA study (SA = satisfaction, CV = quality of life, IN = immune-mediated, FA = pharmacy) consisted of an observational study conducted in 4 hospitals in the Community of Madrid. A cross-sectional analysis was made of adult patients diagnosed with an immune-mediated inflammatory disease who attended the Pharmacy Service. Quality of life was assessed using the EQ-5D-5L questionnaire (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and specific questionnaires: SIBDQ-9, DLQI, PsAQoL, QoL-RA and ASQoL., Results: A total of 578 patients were analyzed (inflammatory bowel disease = 25.3%; psoriasis = 19.7%; spondyloarthropathies = 18.7%; rheumatoid arthritis = 18.5%; psoriatic arthritis = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the global EQ-5D- 5 L was 0.771 (0.2) and the mean (SD) visual analogue scale score was 71.5 (20.0). Type of immune-mediated inflammatory diseases was associated with differences in quality of life showing psoriasis and inflammatory bowel disease higher values of EQ-5D-5L than psoriatic arthritis, rheumatoid arthritis and spondyloarthropathies, p < 0,05 in all comparisons. Patients with RA, IBD, and Ps achieved 70% of the maximum score, while patients with PsA and SpAs did not reach 50% of the maximum possible score. Female gender, a state of moderate/severe disease severity, an older age and a higher number of previous treatments were correlated with worse quality of life. Conversely, persistence to current treatment correlated with better quality of life., Conclusions: Patients with immune-mediated inflammatory diseases have markedly affected quality of life, mainly in the pain/discomfort dimension, especially in those immune-mediated inflammatory diseases with a rheumatological component., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Lineage plasticity is a hallmark of cancer progression that impacts therapy outcomes, yet the mechanisms mediating this process remain unclear. Here, we introduce a versatile in vivo platform to interrogate neuroendocrine lineage transformation throughout prostate cancer progression. Transplanted mouse prostate organoids with human-relevant driver mutations (Rb1 -/- ; Trp53 -/- ; cMyc + or Pten -/- ; Trp53 -/- ; cMyc + ) develop adenocarcinomas, but only those with Rb1 deletion advance to aggressive, ASCL1 + neuroendocrine prostate cancer (NEPC) resistant to androgen receptor signaling inhibitors. Notably, this transition requires an in vivo microenvironment not replicated by conventional organoid culture. Using multiplexed immunofluorescence and spatial transcriptomics, we reveal that ASCL1 + cells arise from KRT8 + luminal cells, progressing into transcriptionally heterogeneous ASCL1 + ;KRT8 - NEPC. Ascl1 loss in established NEPC causes transient regression followed by recurrence, but its deletion before transplantation abrogates lineage plasticity, resulting in castration-sensitive adenocarcinomas. This dynamic model highlights the importance of therapy timing and offers a platform to identify additional lineage plasticity drivers., Competing Interests: Competing interests: C.L.S. is on the board of directors of Novartis, is a cofounder of ORIC Pharmaceuticals and is a co-inventor of the prostate cancer drugs enzalutamide and apalutamide, covered by US patents 7,709,517; 8,183,274; 9,126,941; 8,445,507; 8,802,689; and 9,388,159 filed by the University of California. C.L.S. is on the scientific advisory boards for the following biotechnology companies: Beigene, Blueprint Medicines, Column Group, Foghorn, Housey Pharma, Nextech, PMV Pharma and ORIC. D.P. is on the scientific advisory board of Insitro. The other authors declare no competing interests., (© 2024. The Author(s).)

Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in C. elegans to mimic the human NGPS mutation. These baf-1(G12T) mutant worms displayed multiple phenotypes related to fertility, lifespan, and stress resistance. Importantly, nuclear morphology deteriorated faster during aging in baf-1(G12T) compared to wild-type animals, recapitulating an important hallmark of cells from progeria patients. Although localization of BAF-1(G12T) was similar to wild-type BAF-1, lamin accumulation at the nuclear envelope was reduced in mutant worms. Tissue-specific chromatin binding and transcriptome analyses showed reduced BAF-1 association in most genes deregulated by the baf-1(G12T) mutation, suggesting that altered BAF chromatin association induces NGPS phenotypes via altered gene expression., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation., Material and Methods: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated., Results: (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation., Conclusions: Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background and Aims: Few studies have evaluated frailty in older hypertensive individuals and the most appropriate tools to identify frailty in this population have yet to be identified. This study compared the performance of six frailty instruments in the prediction of 1-year functional decline in older hypertensive outpatients., Methods: The HYPERtension and FRAILty in Older Adults (HYPER-FRAIL) longitudinal pilot study involved hypertensive participants ≥75 years from two geriatric outpatient clinics at Careggi Hospital, Florence, Italy, undergoing identification of frailty with four frailty scales (Fried Frailty Phenotype, Frailty Index [FI], Clinical Frailty Scale [CFS], Frailty Postal Score) and two physical performance tests (Short Physical Performance Battery [SPPB] and gait speed). Prediction of 1-year functional decline (i.e. a ≥ 10-point Barthel Index decrease between baseline and follow-up) was examined based on ROC curve analysis and multivariable logistic regression., Results: Among 116 participants, 24 % reported functional decline. In the ROC curve analyses, FI (AUC=0.76), CFS (AUC=0.77), gait speed (AUC=0.73) and the SPPB (AUC=0.77) achieved the best predictive performance, with FI ≥0.21 and CFS ≥4 showing the highest sensitivity (82 %) and negative predictive value (91 %). Frailty identified with FI, CFS or physical performance tests was associated with an increased risk of 1-year functional decline, independently of baseline functional status and comorbidity burden., Conclusions: FI, CFS and physical performance tests showed similar predictive ability for functional decline in hypertensive outpatients. The CFS and gait speed might be more suitable for clinical use and may be useful to identify non-frail individuals at lower risk of functional decline., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Caregivers' ambivalent feelings toward the care recipient have been found to be associated with depression and anxiety. There is no research linking caregivers' ambivalent feelings and cardiovascular risk. This study was aimed to analyze longitudinally the effect of ambivalence on caregivers' cardiovascular risk, defined by circulating levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and D-dimer., Method: Participants were 121 dementia family caregivers who were assessed three times during a 2-year period. Sociodemographic and health variables, behavioral and psychological symptoms of dementia (BPSD), ambivalent feelings, and C-reactive protein (CRP), IL-6, and D-dimer values were assessed. Mixed linear models were used to analyze the association between variables, including testing whether ambivalent feelings moderated the links between BPSD and biomarkers., Results: Increases over time in D-dimer were associated with increases in ambivalence, older age, female gender, and body mass index (BMI). Increases over time in CRP were associated with increases in BMI, older age, female gender, and the interaction of BPSD with caregivers' ambivalent feelings. The moderation analysis showed that increased BPSD was significantly associated with increased CRP when caregivers experienced high levels of ambivalence ( p = .006). In contrast, BPSD were not significantly associated with CRP when caregivers experienced low levels of ambivalence ( p = .73). Increases in IL-6 were associated with female gender and BMI. The tested model explained 42.85%, 33.15%, and 5.36% of longitudinal variance in CRP, D-dimer, and IL-6 levels, respectively., Conclusion: The findings suggest that high ambivalent feelings are relevant for understanding cardiovascular vulnerability in dementia caregivers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objectives: To evaluate health-related quality of life perceived by patients with the most prevalent immune-mediated inflammatory diseases in Spain: inflammatory bowel disease (IBD), psoriasis (Ps), psoriatic arthritis (AP), rheumatoid arthritis (RA), and spondyloarthropathies (SpAs), and to determine the factors that influence patient quality of life., Methods: The SACVINFA study (SA=satisfaction, CV=quality of life, IN=immune-mediated, FA=pharmacy) consisted of an observational study conducted in 4 hospitals in the Community of Madrid. A cross-sectional analysis was made for adult patients diagnosed with an immune-mediated inflammatory disease who attended the Pharmacy Service. Quality of life was assessed using the EQ-5D-5L questionnaire (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and specific questionnaires: SIBDQ-9, DLQI, PsAQoL, QoL-RA, and ASQoL., Results: A total of 578 patients were analysed (inflammatory bowel disease=25.3%; psoriasis=19.7%; spondyloarthropathies=18.7%; rheumatoid arthritis=18.5%; psoriatic arthritis=17.8%). The mean age (standard deviation) was 49.8 (12.3) years and 50.7% were male. The average score (standard deviation) for the global EQ-5D-5L was 0.771 (0.2) and the mean (standard deviation) visual analogue scale score was 71.5 (20.0). Type of immune-mediated inflammatory diseases was associated with differences in quality of life showing psoriasis and inflammatory bowel disease higher values of EQ5D-5L than psoriatic arthritis, rheumatoid arthritis, and spondyloarthropathies, p<.05 in all comparisons. Patients with RA, IBD, and Ps achieved 70% of the maximum score, while patients with PsA and SpAs did not reach 50% of the maximum possible score. Female gender, a state of moderate/severe disease severity, an older age, and a higher number of previous treatments were correlated with worse quality of life. Conversely, persistence to current treatment correlated with better quality of life., Conclusions: Patients with immune-mediated inflammatory diseases have markedly affected quality of life, mainly in the pain/discomfort dimension, especially in those immune-mediated inflammatory diseases with a rheumatological component., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: People who are homeless are more likely to experience poor mental health and addiction as well as suffering from non-communicable diseases. There is evidence of frailty and accelerated physical ageing among people experiencing homelessness. Appropriate physical rehabilitation and nutritional supplementation strategies can stabilise or reverse frailty and general physical decline, but it is not known how this type of intervention would work in practice in this population., Aim: To evaluate the feasibility and pre-post intervention impact of a low threshold physical rehabilitation intervention with protein supplementation to target physical functioning and frailty in people with problematic substance use who are experiencing homelessness., Methods: The intervention will consist of a 12-week low threshold rehabilitation programme with protein supplementation. Participants will be service users of the Ballyfermot Advance Project, a day services centre for people with addiction issues and experiencing homelessness. Primary outcomes will be feasibility including numbers recruited, retention of participants and adherence to the exercise intervention and protein supplement. Any adverse events will be recorded. Secondary outcomes will be strength and muscular mass, physical performance and lower extremity physical function, pain, frailty and nutritional status., Discussion: An immediate impact may be simply a distraction from difficult circumstances and potentially an improvement of physical health of participants, which can be a conduit for the emergence of other positive behaviours and recovery. Longer term, this study will generate preliminary data on which to inform the design of a definitive randomised controlled trial of physical rehabilitation and protein supplementation, if indicated., Ethics and Dissemination: Ethical approval was granted by the Faculty of Health Sciences Research Ethics Committee in TCD. Study findings will be disseminated through publication into an international peer-reviewed journal and presented at national and international conferences., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Kennedy F et al.)

Widespread public awareness is needed to address health disparities and push for effective and equitable solutions. However, in a high choice media environment, this can only be achieved to the extent that people opt to consume disparity messaging. Drawing on theories of selective exposure, the present research uses a pre-registered online study conducted with U.S. adult participants to examine identity-based predictors of choice exposure to a racial disparity message about the health consequences of air pollution. Findings indicate that racial identity and environmental justice awareness are key predictors of disparity message selection, likely motivated by information utility and a bias toward congenial information. Altogether, results underscore the difficulty of raising awareness of disparities beyond impacted or already well-informed groups and highlight the need to examine more creative messaging strategies in order to broaden public awareness.

Objectives: Streptococcus agalactiae , or Group B Streptococcus (GBS), is a leading cause of neonatal sepsis. Materno-fetal transmission of the microorganisms present in the lower genital tract/perineum is considered to be the most frequent mode for acquisition of infection. It has also been proposed that, in a subset of cases, GBS causes acute chorioamnionitis, intraamniotic infection, and fetal/neonatal sepsis. However, the evidence to support this ascending pathway is derived from microbiologic studies that rely on cultivation methods, which do not have the resolution to determine if the microorganisms causing neonatal sepsis are the same as those found in the amniotic fluid and the vaginal ecosystem., Methods: We used whole genome sequencing of the microorganisms isolated from the vagina, amniotic fluid, chorioamniotic membranes, and neonatal blood (four isolates) in a case of early neonatal sepsis. Using hybrid genome assembly, we characterized the genomic features including virulence factors and antimicrobial resistance in four isolates from the same mother, placenta, and newborn., Results: Whole genome sequencing revealed that the microorganisms in the four clinical isolates corresponded to S. agalactiae sequence type 1, clonal complexes 1, and serotype Ib. Comparative genomic analysis illustrated similar DNA sequences of the four genomes., Conclusions: This study presents the first evidence of the genomic similarity of microorganisms in the vaginal ecosystem, the space between the chorioamniotic membranes of the placenta, amniotic fluid, and neonatal blood., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Rationale: Tobacco use is a risk factor for COVID-19 adverse outcomes. Despite health implications, data conflict regarding COVID-19 and tobacco consumption. We present results from a survey of health behaviors during the pandemic to identify how COVID-19 influenced tobacco behaviors., Methods: A nationally administered, internet-based survey was deployed between May-September 2020. Of respondents, we analyzed participants who reported current smoking and/or vaping. Our primary outcome of interest was change in tobacco or vape use using measures from the Behavioral Risk Factor Surveillance System, as well as whether participants reported that these changes were related to COVID-19. Our principal exposures were previously psychometrically evaluated measures of anxiety, depression, and novel perceived COVID-19 threat scale with additional adjustment for age. We employed multinomial logistic regression to determine associations between these factors and tobacco consumption., Results: We identified 500 respondents who reported ever smoking in their lifetime, 150 of which reported currently smoking at the time of the survey. Of 220 participants who reported any use of vapes, 110 reported currently vaping. Increased perceived threat of COVID-19 was associated with both increased (aRR increase 1.75, 95% CI [1.07-2.86], P = 0.03) and decreased (aRR decrease 1.72 [1.04-2.85], P = 0.03) tobacco consumption relative to no change. There were no significant relationships found between perceived threat of COVID-19 and vaping behavior., Conclusions: As perceived COVID-19 threat increased, people were more likely to increase or decrease their smoking as opposed to continue at the same amount of use, even after controlling for anxiety and depression, both of which are known to affect smoking in either direction. Further study into motivators of changing tobacco consumption behaviors, and how barriers to care from safer-at-home policies and changes in care delivery moderate change in tobacco use will aid planning tobacco reduction interventions during the ongoing and future respiratory viral pandemics., Trial Registration: This manuscript is derived from baseline survey data obtained in the "Understanding Community Considerations, Opinions, Values, Impacts, and Decisions in COVID-19" study., Clinicaltrials: gov registration NCT04373135, registered 04/30/2020., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Long-read sequencing (LRS) enables accurate structural variant detection and variant phasing. When a molecular diagnosis is suspected, target enrichment can reduce the cost and duration of sequencing., Methods: LRS was conducted in five inherited retinal dystrophy (IRD) patients harboring a monoallelic variant in RPE65 that remained uncharacterized after clinical exome sequencing (CES). CRISPR-Cas9 guide RNA probes were designed to target a 31 kb region, including the entire RPE65 locus. The DNA was sequenced on a MinION platform. Short-read ×30 whole-genome sequencing (WGS) was performed for five patients to validate nanopore results., Results: The nanopore sequencing process yielded a median of 271 reads within the targeted region, with a mean depth of 109 and a median read size of 8 kb. All variants identified by CES have been detected using this approach, and no additional RPE65 gene causative variants were found. Nanopore variant detection demonstrated performance akin to short-read WGS at similar coverage levels, although exhibiting increased false positive calls at lower coverage., Discussion: In this study, we explore the advantages of using a targeted approach together with long-read sequencing to identify variants associated with IRD. The results underscore the utility of targeted long reads for characterizing patients affected by rare diseases when first-tier diagnostic tests are non-conclusive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodilla, Núñez-Moreno, Benitez, Romero, Fernández-Caballero, Mínguez, Corton and Ayuso.)

Poor placental development and placental defects can lead to adverse pregnancy outcomes such as pre-eclampsia, fetal growth restriction, and stillbirth. This study introduces two sensors, which use a near-infrared spectroscopy (NIRS) technique to measure placental oxygen saturation transabdominally. The first one, an NIRS sensor, is a wearable device consisting of multiple NIRS channels. The second one, a Multimodal sensor, which is an upgraded version of the NIRS sensor, is a wireless and wearable device, integrating a motion sensor and multiple NIRS channels. A pilot clinical study was conducted to assess the feasibility of the two sensors in measuring transabdominal placental oxygenation in 36 pregnant women (n = 12 for the NIRS sensor and n = 24 for the Multimodal sensor). Among these subjects, 4 participants had an uncomplicated pregnancy, and 32 patients had either maternal pre-existing conditions/complications, neonatal complications, and/or placental pathologic abnormalities. The study results indicate that the patients with maternal complicated conditions (69.5 ± 5.4%), placental pathologic abnormalities (69.4 ± 4.9%), and neonatal complications (68.0 ± 5.1%) had statistically significantly lower transabdominal placental oxygenation levels than those with an uncomplicated pregnancy (76.0 ± 4.4%) ( F (3,104) = 6.6, p = 0.0004). Additionally, this study shows the capability of the Multimodal sensor in detecting the maternal heart rate and respiratory rate, fetal movements, and uterine contractions. These findings demonstrate the feasibility of the two sensors in the real-time continuous monitoring of transabdominal placental oxygenation to detect at-risk pregnancies and guide timely clinical interventions, thereby improving pregnancy outcomes.

Importance: The COVID-19 pandemic prompted rapid development of scarce resource allocation policies (SRAPs) in case demand for critical health services eclipsed capacity., Objective: To test whether a brief educational video could improve knowledge of how the University of California Health's SRAP would be implemented and trust in health systems to implement such policies in accordance with ethical principles during the pandemic., Design, Setting, and Participants: This randomized clinical trial used an educational video intervention embedded in a longitudinal web-based survey and was conducted between May and December 2020 and analyzed during March 2024. A total of 1971 adult participants were enrolled, of whom 939 completed follow-up; participants with matched baseline and follow-up responses were analyzed. California residents were randomized to view the intervention (n = 345) or not (n = 353) and stratified by age, sex, education, racial identity, and self-reported health care worker status. Non-California residents were allocated to the control group (n = 241)., Interventions: A brief (6-minute) "explainer" video that provided an overview of mechanics and ethical principles underpinning the University of California Health SRAP, subtitled in 6 languages., Main Outcomes and Measures: Self-reported survey assessment of knowledge of components of SRAP, graded as correct vs incorrect, and trust graded on a 10-point Likert scale. Anxiety about such policies was graded on a 10-point Likert scale with an a priori noninferiority margin of half of a standard deviation. Participants answered items at baseline and follow-up (approximately 10 weeks after baseline), with randomization occurring between administrations., Results: Of 770 randomized participants with responses at both points, 566 (73.5%) were female, and the median (IQR) age was 43.5 (36-57) years. Intervention participants demonstrated improvement of 5.6 (95% CI, 4.8-6.4; P < .001) more correct knowledge items of 20 vs controls, as well as significant improvements in reported trust in fairness/consistency and honesty/transparency about SRAP implementation. There was no significant change in reported anxiety surrounding SRAP in either treatment or control groups., Conclusions and Relevance: The trial found that a brief educational video is sufficient to explain complex ethical tenets and mechanics of SRAP and improved knowledge of such policies and trust in health systems to implement them equitably while not exacerbating anxiety about potential policy implications. This informs practice by providing a framework for educating people about the use of these policies during future situations necessitating crisis standards of care., Trial Registration: ClinicalTrials.gov Identifier: NCT04373135.

Problem: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction., Method of Study: This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at p < 0.05 or false discovery rate-adjusted q < 0.1., Results: In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%-90%) and 68% (95% CI, 56%-80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data., Conclusions: Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Aim: The aim of this study was to explore the perceptions and satisfaction of last-year nursing students with the Self-Learning Methodology in Simulated Environments (MAES©)., Background: As a learning method, clinical simulation uses elements that replicate real clinical practice scenarios and facilitates the acquisition of competencies and learning objectives. Simulations promote critical thinking, knowledge, techniques and teamwork in nursing students. The Self-Learning Methodology in Simulated Environments (MAES©) is a method that integrates problem-based learning with realistic clinical simulation., Design: A cross-sectional mixed-method study implemented a simulation learning method as part of the mandatory nursing training practice; that was registered in Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/R89PZ)., Methods: Students were invited to complete a cross-sectional questionnaire about satisfaction with the simulation and were asked to participate in an interview about their perceptions on the simulation. All data were collected in December 2023 in a mid-sized southern Spanish university. A total of 69 last-year nursing students were enrolled in the simulation course and were selected using eligibility criteria., Results: Satisfaction measures showed no significant differences across gender, university access, or age (p>0.05 each). However, strong correlations were found between students' preference for the simulation method and perceived effort value (p<0.001 each). Qualitative analysis identified key themes in different stages of simulation (prebriefing, scenario, briefing, debriefing), simulation benefits (learning, usefulness, positive emotions) and challenges (difficulty, realism, time constraints). Despite some realism concerns, overall, students viewed the methodology positively., Conclusions: The findings of this study underscore the vital role of simulation-based learning in nursing education. As the field of nursing continues to evolve, so too must the educational methods we employ, with simulation-based learning standing at the forefront of this transformative journey., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Mental health treatment for psychosexual problems is effective, but treatment rates are low. Metaverse-based therapy offers one solution to increase overall treatment rates. Understanding attitudes towards this novel approach could lead to wider adoption of metaverse-based therapy, resulting in higher treatment rates for psychosexual problems., Methods: Twenty-one participants across three focus groups of different ages shared their perceptions and attitudes about metaverse-based therapy broadly and for treating sexual disorders. A content analysis of the transcribed text from the focus groups using qualitative data analysis software was conducted., Results: Participants identified several perceived benefits of metaverse-based intervention, including avoiding the perceived embarrassment of going to a clinic and accessing patients (a) with diverse physical or mental functionality, (b) living in remote areas and/or (c) balancing different family/work obligations or duties. The two main concerns with metaverse-based therapy were the fear of online therapy being less personal than traditional therapy and the technological fluency needed. Clarifying their acceptance of the therapy, participants reported that they would be more likely to engage in metaverse-based therapy if they trusted their therapist. Also, although it might be effective for mild and moderate disorders, participants were more reluctant about its use for severe mental illness., Conclusions: Results suggest that attitudes towards metaverse-based intervention are mainly positive, since it removes some barriers that hinder access to psychological treatment in general and, specifically, for problems of a sexual nature., Patient and Public Contribution: During the design stage, a person with sexual difficulties was consulted to understand the patient's perspective. Members of the public advised the implementation of the focus groups. Three potential service users were involved in the coding of the text during the content analysis., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470&#95;471del and c.3331&#95;3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901&#95;2902dup) and two in BRCA2 (c.2095C>T and c.4040&#95;4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333-3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278-1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Background: The stay in a critical care unit (CCU) has a serious impact on physical condition causing numerous discomfort factors such as pain or difficulty in communicating. All of these are associated with possible sequelae following discharge from the Intensive Care Unit (ICU) named post-ICU syndrome. The Kolcaba Comfort Theory allows, from a holistic approach, to identify care needs from the patient's perspective using instruments such as the General Comfort Questionnaire (GCQ)., Objectives: To determine the comfort level of patients admitted to the CCU using the GCQ of Kolcaba and to identify the discomfort factors., Methods: Cross-sectional descriptive observational prospective study., Population: 580 patients admitted to adult CCU of two high complexity hospitals from June 2015 to March 2020 with stay ≥24 h were interviewed. Descriptive analysis, Student's t-test and ANOVA and multivariate analysis were performed using SPSS v26 and STATA v16., Results: The mean age was 52,62 (16,21), 357 (61,6%) were male and 434 (74,8%) were believers. The type of admission was planned in 322 (55,5%) and the most prevalent reason for admission was surgical 486 (83,8%). The median pain score (NRS) was 3,00 [0-4] and severity score (APACHE II) was 13,26 (5,89), the median length of stay was 4,00 [2-7] days. The mean comfort level was 3,02 (0,31) showing the highest value Reanimation 3.02 (0.30) and the lowest Trauma and Emergency Unit 2.95 (0.38). Statistically significant differences were found between the units in the comfort level of patients >65 years of age (p = 0.029). The Relief comfort type obtained the lowest mean 2.81 (0.33) and the physical context 2.75 (0.41) in the three units. In the multivariate analysis, statistically significant differences were found between the comfort level and the pain level: no pain (p = 0,000) OR 4,361 CI [2,184-8,707], mild pain (p = 0,000) OR 4,007 CI [2,068-7,763], moderate pain (p = 0,007) OR 2,803 CI [1,328-5,913], and the APACHE II score equal to or greater than 10 (p = 0,000) OR 0,472 CI [0,316-0,705]., Conclusions: The comfort level showed high scores in all three units. The physical and environmental contexts and the relief comfort type negatively affected the perception of comfort. The variables that explained comfort were pain and severity of illness. The evaluation of comfort from the patient's perspective through the GCQ could be considered an indicator of quality of nursing interventions., (Copyright © 2024 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España S.L.U. All rights reserved.)

Background: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population., Methods: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected., Results: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs., Conclusions: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Intracellular pH (pHi) dynamics regulate normal cell function, and dysregulated pHi dynamics is an emerging hallmark of cancer (constitutively increased pHi) and neurodegeneration (constitutively decreased pHi). However, the molecular mechanisms by which pHi dynamics regulate cell biology are poorly understood. Here, we discovered that altering pHi in normal human breast epithelial cells triggers global transcriptional changes. We identified 176 genes differentially regulated by pHi, with pHi-dependent genes clustering in signaling and glycolytic pathways. Using various normal epithelial cell models, we showed pH-dependent Notch homolog 1 protein expression, with increased protein abundance at high pHi. This resulted in pH-dependent downstream signaling, with increased Notch homolog 1 signaling at high pHi. We also found that high pHi increased the expression of glycolytic enzymes and regulators of pyruvate fate, including lactate dehydrogenase and pyruvate dehydrogenase kinase. These transcriptional changes were sufficient to alter lactate production, with high pHi shifting these normal epithelial cells toward a glycolytic metabolism and increasing lactate production. Thus, pHi dynamics transcriptionally regulate signaling and metabolic pathways in normal epithelial cells. Our data reveal new molecular regulators of pHi-dependent biology and a role for increased pHi in driving the acquisition of cancer-associated signaling and metabolic changes in normal human epithelial cells., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Emerging theories emphasize the crucial role of allostasis (anticipatory and adaptive regulation of the body's biological processes) and interoception (integration, anticipation, and regulation of internal bodily states) in adjusting physiological responses to environmental and bodily demands. In this review, we explore the disruptions in integrated allostatic interoceptive mechanisms in psychiatric and neurological disorders, including anxiety, depression, Alzheimer's disease, and frontotemporal dementia. We assess the biological mechanisms associated with allostatic interoception, including whole-body cascades, brain structure and function of the allostatic interoceptive network, heart-brain interactions, respiratory-brain interactions, the gut-brain-microbiota axis, peripheral biological processes (inflammatory, immune), and epigenetic pathways. These processes span psychiatric and neurological conditions and call for developing dimensional and transnosological frameworks. We synthesize new pathways to understand how allostatic interoceptive processes modulate interactions between environmental demands and biological functions in brain disorders. We discuss current limitations of the framework and future transdisciplinary developments. This review opens a new research agenda for understanding how allostatic interoception involves brain predictive coding in psychiatry and neurology, allowing for better clinical application and the development of new therapeutic interventions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as "stress signals" in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues., Results: Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs., Conclusion: Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes., (© 2024. The Author(s).)

Objectives: To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses., Material and Methods: Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple studies., Results: VMAP (http://vmapapp.org) visualizes 3880 vaginal microbiome samples of 1402 pregnant individuals from 11 studies, aggregated via open-source tool MaLiAmPi. Visualized features include diversity measures, VALENCIA community state types, and composition (phylotypes, taxonomy) that can be filtered by various categories., Discussion: This work represents one of the largest and most geographically diverse aggregations of the vaginal microbiome in pregnancy to date and serves as a user-friendly resource to further analyze vaginal microbiome data and better understand pregnancies and associated outcomes., Conclusion: VMAP can be obtained from https://github.com/msirota/vmap.git and is currently deployed as an online app for non-R users., Competing Interests: Antonio Parraga-Leo and Patricia Diaz-Gimeno are receiving hononaria from the IVI Foundation. All other authors declare no financial or non-financial competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Here we describe and illustrate Pleromacanastrense sp. nov and Pleromaviscosa sp. nov. two new species of the Melastomateae tribe from Serra da Canastra National Park, Minas Gerais, Brazil. We also provide an updated identification key for the members of the tribe that occur in this Protected Area. Pleromacanastrense sp. nov. has coriaceous leaves, broadly ovate to orbicular leaf blade, entire and adpressed-strigose margin, 11-17 basal acrodromous veins, and flowers with white petals. Pleromaviscosa sp. nov. has the younger branches, both side of the leaf blade, bracteoles, hypanthium, and sepals, densely covered by viscous trichomes, as well as prominent secondary veins on the abaxial surface of the blade. Both species have stamens with a short pedoconnective and an inconspicuous ventral appendage. In addition to the descriptions of new species, we present comments, geographic distribution data, conservation status and images of plants in the field. We recommend that P.canastrense and P.viscosa should be included as of 'Least Concern' (LC) in the IUCN Red List., Competing Interests: The authors have declared that no competing interests exist., (Rosana Romero, Rodrigo Pereira Silva, Paulo José Fernandes Guimarães.)

The intragastric balloon (IGB) is recognised as a minimally invasive intervention for the treatment of obesity. Here, we detail a rare and life-threatening complication stemming from this procedure. A female patient in her 40s, who had an IGB in situ for 14 months, presented at the emergency department with septic shock characterised by abdominal guarding and emesis. These symptoms were a direct result of IGB-induced bowel obstruction. We emphasise that the patient missed the recommended 6-month removal window, which in our opinion is the decisive cause leading to deflated balloon migration and subsequent complications. In the course of managing multiple critical events, the patient required multiple operations related to the bowel obstruction, numerous nutritional and psychological challenges. Currently, the patient is living with short bowel syndrome, secondary to the chronic intestinal failure, necessitating the administration of parenteral nutrition 6 days per week., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

(1) Background: Pulmonary hypertension (PH) increases pulmonary vascular resistance and right ventricular (RV) afterload. Assessment of RV systolic function in PH using RV fractional area change (RV FAC) as a marker directly correlates with mortality and the need for extracorporeal membrane oxygenation (ECMO). However, few studies have assessed neurodevelopmental outcomes. We hypothesize that cardiac RV systolic dysfunction with lower RV FAC is associated with worse neurodevelopmental impairment (NI). (2) Methods: Retrospective study of 42 subjects with PH to evaluate neurodevelopmental outcomes in the first two years of life based on (i) subjective assessment of RV systolic function and (ii) RV FAC, a specific echocardiographic marker for RV function. (3) Results: Subjects from the initial study cohort ( n = 135) with PH who had long-term follow-up were divided into RV dysfunction (study, n = 20) and non-RV dysfunction (control, n = 22) groups. RV FAC in the study vs. control group (0.18 vs. 0.25) was lower ( p = 0.00017). There was no statistically significant difference in NI either with RV dysfunction or lower RV FAC. Although not significant, RV dysfunction was associated with longer mean duration of mechanical ventilation, time on ECMO, and length of stay. In the initial cohort (135), mortality was 16.3% and the percentage of NI was 62%. (4) Conclusions: Neonatal pulmonary hypertension is associated with a high degree of neurodevelopment impairment. Early RV systolic dysfunction, as identified by RV FAC, was not an optimal predictive biomarker for infants with PH and neurodevelopmental impairment.

Background: Severe hepatitis cases in children are increasingly recognized, but the exact etiology remains unknown in a significant proportion of patients. Cases of indeterminate severe hepatitis (iSH) may progress to indeterminate pediatric acute liver failure (iPALF), so understanding its immunobiology is critical to preventing disease progression. Hemophagocytic lymphohistiocytosis (HLH) is a systemic hyperinflammatory disorder associated with T-cell and macrophage activation with liver injury., Objectives: We hypothesized that a high proportion of patients with iSH demonstrate systemic T-cell activation similar to HLH before developing iPALF and that the degree of T-cell activation in iSH might correlate with outcomes., Methods: From 2019 to 2022, 14 patients with iSH and 7 patients with PALF of known, nonimmune etiology were prospectively enrolled. We compared immune signatures of iSH, HLH, known PALF, and healthy controls., Results: We found that patients with iSH have increased CD8 + T-cell activation and high IFN-γ activity similar to HLH. The amplitude of CD8 + T-cell activation was predictive of iSH progression to iPALF. We also found that in patients with iSH, ferritin had only modest elevation. However, the ratio of age-normalized plasma soluble IL-2 receptor to ferritin level can distinguish iSH from known PALF and HLH. As proof of concept, we report that in 3 patients with steroid-refractory iSH, emapalumab, an IFN-γ blocking antibody used in combination with steroids, improved liver function and may have prevented progression to PALF., Conclusions: Flow-based T-cell activation markers could help in early identification and risk stratification for targeted intervention in patients with iSH., Competing Interests: Disclosure statement Supported by National Heart, Lung, and Blood Institute (grant 1K08HL141635-01A1), the Atlanta Pediatric Scholars Program K12 Scholar (grant K12HD072245 to S.C.) and T32 (T32DK108735 to T.M.). Contributions were received from the Henagan Foundation (to S.C.), the Seckman family (to S.C.), and the Statham family (to S.C.) for ongoing research support. Disclosure of potential conflict of interest: S. Chandrakasan served on the ad hoc advisory boards of Pharming, X4, SOBI, and Electra Therapeutics. R. Marsh is an employee of Pharming. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n = 160), individuals who had psychotic experiences (n = 157), patients who experienced a first episode of psychosis (FEP, n = 352), and individuals with chronic SCZ or SAD (n = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α 4 β 2 ) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis., (© 2024. The Author(s).)

Lignin valorization through heterogeneous photocatalysis is a promising pathway for obtaining value-added products, including chemical building blocks, biofuels, etc. However, several challenges still demand attention and resolution in this field. One of the key parameters in the heterogeneous photocatalytic process is the synthesis of efficient photocatalysts that can accomplish efficient and selective reactions. Selective conversion of lignin can be achieved by using heterojunction photocatalysts which can efficiently separate charge carriers' and promote selective reactions by band structure modulation. This work details a straightforward approach for synthesizing heterojunction photocatalysts based on Bi 4 Ti 3 O 12 and BiOI involving the hydrothermal and co-precipitation methods. Additionally, the synthesized composites were employed in the selective oxidation of veratryl alcohol, a lignin-derived model compound, to produce high-value-added veratraldehyde. The experimental results showed that the BiOI/Bi 4 Ti 3 O 12 heterojunction (12.5 mol % BiOI) showed superior activity with a veratraldehyde yield of 5.4 and 27.2 times higher than those of Bi 4 Ti 3 O 12 and BiOI, respectively. The mechanistic studies revealed that the improved activity and selectivity were due to the enhanced charge carriers' separation and the suppression of reactive oxygen species formation through modulation of band structure. This study allows a green approach to lignin-derived biomass valorization to obtain high-value chemicals., (© 2024 Wiley-VCH GmbH.)

The use of pesticides in viticulture may play a crucial role in ensuring the health and quality of grapes. This review analyzes the most common pesticides used, illustrating their classification and toxicity, and their variations throughout the winemaking process. Fungicides are generally harmless or mildly toxic, whereas insecticides are classified as either highly or moderately hazardous. Potential alternatives to synthetic pesticides in wine production are also reviewed, thereby including biopesticides and biological agents. Analytical methods for detecting and quantifying pesticide residues in wine are then described, including liquid chromatography and gas chromatography coupled with mass spectrometry. This review also discusses the impact of the winemaking process on pesticide content. Pesticides with strong hydrophobicity were more likely to accumulate in solid byproducts, whereas hydrophilic pesticides were distributed more in the liquid phase. Grape's skin contains lipids, so hydrophobic pesticides adsorb strongly on grape surfaces and the clarification has been shown to be effective in the reduction of hydrophobic compounds. Therefore, the final wine could have more quantities of hydrophilic pesticides. Alcoholic fermentation has been shown to be crucial in pesticide dissipation. However, pesticide residues in wine have been shown an antagonistic effect on yeasts, affecting the safety and quality of wine products. Therefore, proteomic and genomic analyses of yeast growth are reviewed to understand the effects of pesticides on yeast during fermentation. The last section describes new effective methods used in removing pesticides from grapes and wine, thereby improving product quality and reducing harmful effects., (© 2024 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Background: Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified., Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (n cases  = 169 and n controls  = 298, ages 16-70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning., Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences., Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Meaning-centered psychotherapy (MCP) has been found to be effective in improving meaning in life and increasing fulfillment in participants with cancer. However, to date, no previous studies have compared MCP with evidence-based treatments such as cognitive behavioral therapy (CBT). The aim of this study was to analyze the differential efficacy of MCP, compared to CBT, in participants with cancer. The study is a randomized controlled trial with 76 participants, n = 41 (MCP) and n = 35 (CBT). At posttreatment, the MCP intervention for cancer survivors was more effective than CBT in increasing the presence of meaning in life, purpose and meaning in life, and life goals. Moreover, our results showed that, at posttreatment and the 6-month follow-up, MCP and CBT were similarly effective in improving depression and developing posttraumatic growth. This study suggests that MCP could be more effective than CBT in improving meaning in life, purpose, and life goals, and equally effective as CBT in improving depression and posttraumatic growth, in cancer survivors., (Copyright © 2024. Published by Elsevier Ltd.)

This study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video-based intervention for teaching respiratory physiology and anatomy to medical students in resource-limited settings. A series of short video lectures on pleural anatomy, pulmonary physiology, and pathophysiology was created using Lightboard and screen capture technology. These were uploaded to YouTube and Google Drive and made available to 1st-3rd year medical students at two Latin American universities for 1 week. Employing a parallel-convergent mixed methods design, we conducted surveys, focus groups, interviews, and pre/post testing for qualitative and quantitative data. Thematic Analysis was used to analyze qualitative data and McNemar's test for quantitative analysis. Seventy-six students participated. The videos' short format, interactivity, and Lightboard style were highly valued for their flexibility, time efficiency, and educational impact. Students recognized their clinical relevance and trusted their content, suggesting potential applicability in similar settings. Despite infrastructure and connectivity challenges, the use of flexible streaming and downloadable options facilitated learning. Survey results indicated high levels of feasibility (99%), appropriateness (95%), and acceptability (95%), with significant knowledge gains observed (37% correct pre-test answers vs. 56% post-test, p < 0.0001). Our findings demonstrate high acceptability, appropriateness, feasibility, and efficacy of a targeted asynchronous education centered on short-format videos in resource-limited settings, enabling robust learning despite local barriers. Flexible access is key for overcoming localized barriers. Taking an adaptive, learner-centered approach to content creation and delivery to address constraints was pivotal to success. Our modular videos could serve as versatile models for flexible education in resource-constrained settings., (© 2024 American Association for Anatomy.)

We developed an algorithm for automatically analyzing scattering-based light sheet microscopy (sLSM) images of anal squamous intraepithelial lesions. We developed a method for automatically segmenting sLSM images for nuclei and calculating seven features: nuclear intensity, intensity slope as a function of depth, nuclear-to-nuclear distance, nuclear-to-cytoplasm ratio, cell density, nuclear area, and proportion of pixels corresponding to nuclei. 187 images from 80 anal biopsies were used for feature analysis and classifier development. The automated nuclear segmentation method provided reliable performance with the precision of 0.97 and recall of 0.91 when compared with the manual segmentation. Among the seven features, six showed statistically significant differences between high-grade squamous intraepithelial lesion (HSIL) and non-HSIL (non-dysplastic or low-grade squamous intraepithelial lesion, LSIL). A classifier using linear support vector machine (SVM) achieved promising performance in diagnosing HSIL versus non-HSIL: sensitivity of 90%, specificity of 70%, and area under the curve (AUC) of 0.89 for per-image diagnosis, and sensitivity of 90%, specificity of 80%, and AUC of 0.92 for per-biopsy diagnosis., Competing Interests: The University of Arizona has a technology-licensing agreement with ArgosMD on the reflectance confocal microscopy technology. DK has the rights to receive royalties as a result of this licensing agreement. DK serves as a scientific advisor to ArgosMD. Conflicts of interest resulting from this interest are being managed by the University of Arizona in accordance with its policies., (© 2024 Optica Publishing Group.)

Beach volleyball (BV) is an intermittent sport characterised by short-duration and highly demanding activities with low intensity periods. Establishing if players' jump ability is influenced by sand granulometry is a useful information for sport scientists, coaches and players. This study aimed to assess the possible differences in the kinetics parameters of the vertical jump on different types of sand performed by BV players. Twelve elite female players performed six countermovement jumps (CMJs) in three different surface conditions (fine sand, reference, coarse sand) in a random counterbalanced order (216 jumps). A generalised mixed model approach detected differences for CMJ model in total duration (p: 0.016), eccentric phase duration (p: 0.007), concentric phase duration (p: 0.011), time to peak power (p: < 0.001), time to peak force (p: 0.014), maximum rate force development concentric phase (p: 0.004), maximum velocity (p: 0.028) and peak power eccentric (p: 0.018). Coarse sand decreases the time spent jumping compared to fine sand, without a penalty to jump height. Coaches and athletes should take this information into account to enhance their understanding of practice strategies and game conditions. One might anticipate a faster pace in games played on coarse sand and a slower pace on fine sand.