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Abstract Background Although crackles on chest auscultation represent a fundamental component of the diagnostic suspect for fibrotic interstitial lung disease (ILD), their reliability has not been properly studied. We assessed the agreement among respiratory physicians on the presence and changes over time of audible crackles collected in a prospective longitudinal cohort of patients with fibrotic ILD. Methods Lung sounds were digitally recorded at baseline and after 12 months at eight anatomical sites. Nine respiratory physicians blindly assessed randomized couples of recordings obtained from the same anatomical site at different timepoints. The physicians indicated the presence of crackles in individual recordings and which recording from each couple eventually had more intense crackles. Fleiss’ kappa coefficient was used to measure inter- and intra-rater agreement. Results Fifty-two patients, mostly with a diagnosis of IPF (n = 40, 76.9%) were prospectively enrolled between October 2019 and May 2021. The final acoustic dataset included 702 single recordings, corresponding to 351 couples of recordings from baseline and 12-months timepoints. Kappa coefficient was 0.57 (95% CI 0.55–0.58) for the presence of crackles and 0.42 (95% CI 0.41–0.43) for acoustic change. Intra-rater agreement, measured for three respiratory physicians on three repeated assessments, ranged from good to excellent for the presence of crackles (κ = 0.87, κ = 0.86, κ = 0.79), and from moderate to good for acoustic change (κ = 0.75, κ = 0.76, κ = 0.57). Conclusions Agreement between respiratory physicians for the presence of crackles and acoustic change was acceptable, suggesting that crackles represent a reliable acoustic finding in patients with fibrotic ILD. Their role as a lung-derived indicator of disease progression merits further studies.

Children are at high risk of exposure to potentially traumatic events (PTEs) during early childhood. This developmental period, marked by rapid growth in fundamental skills, may render children particularly vulnerable to adverse developmental effects. Embedding universal trauma-informed supports within early childhood education (ECE) settings has the potential to mitigate the negative consequences of early exposure to PTEs; yet there is a lack of early childhood trauma-informed prevention and intervention programming. To address this need, a collaborative partnership via a participatory research approach was formed between an academic partner and several early childhood education centers in a large urban public school district primarily serving youth of color. This exploratory study describes the development of the "Ready to Learn through Relationships (RLR) Program" that emerged from this partnership. The RLR program is based on the National Child Traumatic Stress Network (NCTSN) guidelines for school-based models of trauma-informed care (TIC) and the "boots on the ground" experiences of the participating school district's early childhood personnel. It utilizes implementation coaching to promote program installation and sustainability. Results demonstrate high levels of need for the program, as well as its feasibility and acceptability. Recommendations for future refinement, implementation, and evaluation efforts are discussed.

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis. Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids, such as docosahexaenoic acid, and exercise in Parkinson’s disease, we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway. First, mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation. Four weeks after lesion, animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks. During this period, the animals had access to a running wheel, which they could use or not. Docosahexaenoic acid treatment, voluntary exercise, or the combination of both had no effect on (i) distance traveled in the open field test, (ii) the percentage of contraversive rotations in the apomorphine-induction test or (iii) the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta. However, the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum. Compared to docosahexaenoic acid treatment or exercise alone, the combination of docosahexaenoic acid and exercise (i) improved forelimb balance in the stepping test, (ii) decreased the striatal DOPAC/dopamine ratio and (iii) led to increased dopamine transporter levels in the lesioned striatum. The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

Abstract It has been thought that Io’s many paterae may contain lava lakes, but observations by NASA’s Galileo spacecraft at sufficiently high resolution were limited to a few locations, such as Loki Patera. Data acquired by NASA’s Juno mission in May 2023 reveal a common set of thermal characteristics for at least ten paterae on Io, with bright (hot) “thermal rings” around the perimeter of their floors. Loki, Surt, Fuchi, Amaterasu, Mulungu, Chors, and Dazhbog Patera, and four unnamed paterae, all show the same pattern of surface temperature. This new Juno/JIRAM data suggests that hot rings around paterae are a common phenomenon, and that they are indicative of active lava lakes. All the investigated paterae lack recent lava flows on their flanks, suggesting that at the time of observations, the level of the lake was not high enough to overflow the rim. These observations provide insight about the characteristics of paterae’s activity, which may involve either central upwelling of magma, or up-and-down “piston-like” vertical motion of the lake surface. Tidal forces, which are extreme at Io, could play a role as well. Future observations from Juno, particularly during the closest flybys, may indicate which mechanism is more plausible.

Student leadership identity is fast becoming one of the most critical challenges educational institutions face today. However, mental health counselors may be limited in the amount of education and training received as they become leaders in the field. There is currently no known mandate at the master's level for leadership embedded within the counseling curriculum in the educational environment, although research suggests otherwise. The purpose of this correlational predictive empirical study was to investigate leadership identity characteristics as measured by the Socially Responsible Leadership Scale, Revision 2 (SLRS-R2), moderated by demographic factors. Multiple regression analysis was used to determine outcome measures of the SLRSR2 relating to leadership. Conclusions and suggestions for future practice regarding leadership skill development are provided.

There is now compelling evidence for the presence of pathological forms of Tau in tissues of both patients and animal models of Huntington's disease (HD). While the root cause of this illness is a mutation within the huntingtin gene, a number of studies now suggest that HD could also be considered a secondary tauopathy. However, the contributory role of Tau in the pathogenesis and pathophysiology of this condition, as well as its implications in cellular toxicity and consequent behavioral impairments are largely unknown. We therefore performed intracerebral stereotaxic injections of recombinant human Tau monomers and fibrils into the knock-in zQ175 mouse model of HD. Tau fibrils induced cognitive and anxiety-like phenotypes predominantly in zQ175 mice and increased the number and size of insoluble mutant huntingtin (mHTT) aggregates in the brains of treated animals. To better understand the putative mechanisms through which Tau could initiate and/or contribute to pathology, we incubated StHdh striatal cells, an in vitro model of HD, with the different Tau forms and evaluated the effects on cell functionality and heat shock proteins Hsp70 and Hsp90. Calcium imaging experiments showed functional impairments of HD StHdh cells following treatment with Tau fibrils, as well as significant changes to the levels of both heat shock proteins which were found trapped within mHTT aggregates. The accumulation of Hsp70 and 90 within aggregates was also present in mouse tissue which suggests that alteration of molecular chaperone-dependent protein quality control may influence aggregation, implicating proteostasis in the mHTT-Tau interplay.

BackgroundEosinophilic esophagitis (EoE) is a chronic and progressive type 2 inflammatory disease affecting the esophagus. Its prevalence has increased in recent years due to increased awareness, evolving clinical guidelines, and heightened sensitivity among healthcare professionals managing the condition. The exact causes behind EoE’s development remain unknown, and its clinical presentation varies, often leading to significant diagnostic delays depending on the age at which symptoms manifest. Consequently, achieving long-term disease control through heightened awareness becomes imperative. EoE generates a significant clinical burden, resulting in substantial economic consequences for patients, healthcare systems, and society. This study aimed to assess the economic and social impacts on EoE patients within the Italian context.MethodsA cost-of-illness analysis was conducted from two perspectives: the National Health System (NHS) and the societal perspective. This analysis encompassed direct healthcare, indirect healthcare, and non-healthcare costs. Data were collected and assessed through a survey administered to a panel of expert clinicians and EoE-affected patients.ResultsManaging EoE incurs a significant burden on healthcare systems, amounting to €6,852.28 per patient per year. The primary cost component appears to be direct costs, comprising 60.73% of the total cost per patient for this condition, while indirect costs contribute to 29.68% of the overall management expenses.ConclusionThis analysis underscores a substantial financial burden on both the healthcare system and patients affected by eosinophilic esophagitis. It emphasizes the imperative need for a continuous and combined effort from clinicians, patients, and families to promptly recognize symptoms and adaptive behavior to mitigate diagnostic delays.

Mind-mindedness is associated with positive developmental outcomes. However, much of the literature uses mostly White, middle to high socioeconomic status (SES) samples despite evidence that the benefits of mind-mindedness may vary based on degree of social risk. Additionally, few studies have examined relations between mind-mindedness and language development. The current study investigates whether mind-mindedness predicts children's language development and behavioral functioning and if family history of childhood maltreatment moderates the relation of mind-mindedness to these outcomes. Participants were 98 mothers (49.0% Black, 24.5% White, 13.3% Latina, 7.2% multiracial; 81.6% low SES per Hollingshead classifications) and their children (49 boys, 49 girls) from the Rochester, New York area recruited at Time 1 (M[subscript age] = 13.34 months) and followed up twice (M[subscript ages] = 27.51 [Time 2] and 39.31 months [Time 3]). Mother-child dyads participated in videotaped free play interactions at Times 1 and 2. Using transcripts of these interactions, we coded mind-mindedness at Times 1 and 2 and children's internal state language at Time 2. Mothers reported on children's behavioral functioning at Time 3. Findings revealed that Time 2 mind-mindedness predicted fewer Time 3 behavioral difficulties in children from maltreating families but did not predict behavioral difficulties in children from nonmaltreating families. Additionally, Time 1 mind-mindedness predicted children's Time 2 use of decontextualized internal state language. Findings highlight the importance of examining mind-mindedness in higher risk populations and how mind-mindedness can be leveraged as a protective factor to prevent future maladjustment in children at risk for adverse outcomes.

Abstract Background Seasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy. Methods To estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted. Results Assuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69. Conclusions The study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

A number of post-mortem studies conducted in transplanted Huntington’s disease (HD) patients from various trials have reported the presence of pathological and misfolded proteins, in particular mutant huntingtin (mHtt) and phosphorylated tau neuropil threads, in the healthy grafted tissue. Here, we extended these observations with histological analysis of post-mortem tissue from three additional HD patients who had received similar striatal allografts from the fetal tissue transplantation trial conducted in Los Angeles in 1998. Immunohistochemical staining was performed using anti-mHtt antibodies, EM48 and MW7, as well as anti-hyperphosphorylated tau antibodies, AT8 and CP13. Immunofluorescence was used to assess the colocalization of EM48+ mHtt aggregates with the neuronal marker MAP2 and/or the extracellular matrix protein phosphacan in both the host and grafts. We confirmed the presence of mHtt aggregates within grafts of all three cases as well as tau neuropil threads in the grafts of two of the three transplanted HD patients. Phosphorylated tau was also variably expressed in the host cerebral cortex of all three subjects. While mHtt inclusions were present within neurons (immunofluorescence co-localization of MAP2 and EM48) as well as within the extracellular matrix of the host (immunofluorescence co-localization of phosphacan and EM48), their localization was limited to the extracellular matrix in the grafted tissue. This study corroborates previous findings that both mHtt and tau pathology can be found in the host and grafts of HD patients years post-grafting.

Summary: Background: The search for factors beyond the radiotherapy dose that could identify patients more at risk of developing radio-induced toxicity is essential to establish personalised treatment protocols for improving the quality-of-life of survivors. To investigate the role of the intestinal microbiota in the development of radiotherapy-induced gastrointestinal toxicity, the MicroLearner observational cohort study characterised the intestinal microbiota of 136 (discovery) and 79 (validation) consecutive prostate cancer patients at baseline radiotherapy. Methods: Gastrointestinal toxicity was assessed weekly during RT using CTCAE. An average grade >1.3 over time points was used to identify patients suffering from persistent acute toxicity (endpoint). The microbiota of patients was quantified from the baseline faecal samples using 16S rRNA gene sequencing technology and the Ion Reporter metagenomic pipeline. Statistical techniques and computational and machine learning tools were used to extract, functionally characterise, and predict core features of the bacterial communities of patients who developed acute gastrointestinal toxicity. Findings: Analysis of the core bacterial composition in the discovery cohort revealed a cluster of patients significantly enriched for toxicity, displaying a toxicity rate of 60%. Based on selected high-risk microbiota compositional features, we developed a clinical decision tree that could effectively predict the risk of toxicity based on the relative abundance of genera Faecalibacterium, Bacteroides, Parabacteroides, Alistipes, Prevotella and Phascolarctobacterium both in internal and external validation cohorts. Interpretation: We provide evidence showing that intestinal bacteria profiling from baseline faecal samples can be effectively used in the clinic to improve the pre-radiotherapy assessment of gastrointestinal toxicity risk in prostate cancer patients. Funding: Italian Ministry of Health (Promotion of Institutional Research INT-year 2016, 5 × 1000, Ricerca Corrente funds). Fondazione Regionale per la Ricerca Biomedica (ID 2721017). AIRC (IG 21479).

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose

Objective: we aim to illustrate step by step the technique of enucleoresection of renal mass during robot-assisted partial nephrectomy (RAPN). Patient and surgical procedure: 72-year-old man affected by asymptomatic and incidental small renal mass in the middle third of the left kidney. The diameter of the renal mass was 3 cm on preoperative imaging, with a PADUA score of 7. We performed left transperitoneal RAPN with selective clamping. After the enucleoresection, medullary and cortical sutures were performed. A hemostatic agent was applied at the end of the procedure. Results: Intraoperative blood loss was 50 ml, with an ischemia time of 15 min. Postoperative hemoglobin was 14.8 g/dL and the creatinine was 0.69 mg/dL. On the third post-operative day, the drain was removed and the patient was discharged on the same day. No postoperative complications or recurrences were found during the 6-month follow-up. Conclusion: partial nephrectomy maximizes the amount of healthy renal parenchyma spared. Evidence supports the adoption of this technique whenever feasible.

Data collected from a study of school libraries in Massachusetts provide source material that identifies barriers and enablers related to equitable access and meaningful use of school library resources and services. These quantitative and qualitative survey data supplied by school librarians across rural, urban, and suburban schools describe staffing, resources, instruction, and funding which suggest barriers and enablers related to equitable access and meaningful use. An in-depth analysis reveals underlying factors that determine policies and practices such as traditional library values, educational beliefs, and social justice principles that are operational in the access and use of school libraries.

Despite findings that developmental timing of maltreatment is a critical factor in predicting subsequent outcomes, children's developmental stage is understudied in maltreatment research. Moreover, childhood maltreatment is associated with the development of maladaptive peer relationships and psychopathology, with social cognition identified as a process underlying this risk. The current study uses structural equation modeling to examine the impact of developmental timing of maltreatment (i.e., infancy through preschool versus elementary and middle-school years) on psychopathology via negative perceptions of peer relationships. Multi-informant methods were used to assess 680 socioeconomically disadvantaged children. Results did not support differential effects of early versus later maltreatment on children's internalizing symptomatology or disruptive behavior, but indicated that chronic maltreatment, relative to episodic maltreatment, has more severe consequences for children's internalizing symptomatology. Results further support the mediating role of children's perceptions of relationships in the effect of maltreatment on negative developmental outcomes.

Racial and ethnic disproportionality in discipline (REDD) represents a longstanding and pervasive issue in the United States educational system. However, researchers and interventionists have not sufficiently provided educators with appropriate frameworks and feasible tools to disrupt REDD and promote equity. The goal of this paper is to present a framework of eight malleable factors associated with REDD and describe the Disproportionality in Discipline Assessment for Schools (DDAS). The DDAS is a suite of user-friendly tools based on this framework, designed to help school teams identify and address REDD. Two studies are described. Study 1 presents the results of educator feedback on a presentation of the framework and the DDAS in terms of their perception of its feasibility, usability, and validity/logical soundness. Study 2 presents the process of applying the DDAS in four real-world school settings. Results indicated that the framework and the DDAS were useful and feasible tools to help schools increase equity and address REDD. Modifications to the framework and the DDAS were made to improve validity and appropriateness.