bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic food consumption during pregnancy and symptoms of neurodevelopmental disorders at 8 years of age in the offspring: the Norwegian Mother, Father and Child Cohort Study (MoBa)
Authors: Instanes Johanne T. , Solberg Berit S. , Kvalvik Liv G. , Klungsøyr Kari , Posserud Maj-Britt R. , Hartman Catharina A. , Haavik Jan
Published: October 2024

Background

Partially driven by public concerns about modern food production practices, organic food has gained popularity among consumers. However, the impact of organic food consumption during pregnancy on offspring health is scarcely studied. We aimed to investigate the association between maternal intake of organic food during pregnancy and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring at 8 years of age.

Methods

This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). The total study sample included 40,707 mother–child pairs (children born 2002–2009). Organic food consumption during pregnancy was assessed by six questions from a food frequency questionnaire in mid-pregnancy (sum score 0–18). Symptoms of ADHD and ASD in the offspring aged 8 years were measured by ADHD (0–54) and ASD (0–39) symptom scores based on the Parent/Teacher Rating Scale for Disruptive Behaviour disorders and the Social Communication Questionnaire. Associations between maternal intake of organic food during pregnancy and symptoms of ADHD and ASD in the offspring were analyzed using regression models with adjustment for covariates such as maternal anxiety and depression, including sibling analysis.

Results

Mean ADHD and ASD symptom scores in the offspring differed only slightly by maternal intake of organic food. The covariate-adjusted unstandardized regression coefficient (adjusted(Adj)beta) with 95% confidence interval for the ADHD symptom score with one unit increase in organic food sum score was 0.03 (0.01, 0.05). Similarly, Adjbeta for autism symptom score was 0.07 (0.04, 0.10). For ADHD, the adjusted estimates weakened when adjusting for maternal symptoms of ADHD. The sibling analyses showed no significant results with Adjbeta − 0.07 (− 0.15, 0.01) and − 0.001 (− 0.12, 0.12) for ADHD and ASD outcomes, respectively.

Conclusions

We observed weak positive associations between frequent maternal organic food consumption during pregnancy and offspring ADHD and ASD symptom levels at 8 years of age. This trend weakened or disappeared after adjusting for maternal symptoms of ADHD, and in sibling analyses, suggesting that the associations mainly reflect genetic confounding. Our study indicates that consumption of organic food during pregnancy should neither be considered a risk factor nor protective against symptoms of ADHD and ASD in offspring.
Reducing rehospitalization in cardiac patients: a randomized, controlled trial of a cardiac care management program (“Cardiolotse”) in Germany
Authors: Schüttig Wiebke , Darius Harald , Reber Katrin C. , Coors Marie , Flothow Amelie , Holzgreve Alfred , Karmann Sebastian , Stürtz Anica , Zöller Rebecca , Kropp Saskia , Riesner Petra , Sundmacher Leonie
Published: October 2024

Background

We conducted a prospective, randomized, controlled, two-group parallel trial investigating the effectiveness of a care management program employing cardiac care navigators providing post-discharge support to patients compared to standard care.

Methods

The intervention commenced in 2019/2020 for 2862 patients hospitalized with heart failure, coronary heart disease, or cardiac arrhythmias in departments of cardiology across eight participating sites of a hospital group in Berlin, Germany. We analyzed the results using an intention-to-treat approach. The primary outcome was the all-cause rehospitalization rate after 12 months. Secondary outcomes included rehospitalizations due to one of the qualifying cardiac diagnoses, duration of rehospitalization, mortality, health-related quality of life, and several process indicators.

Trial data were collected from a combination of face-to-face and phone interviews conducted by hospital staff throughout the 12-month follow-up period using standardized questionnaires. Administrative claims data were provided by a large statutory health insurer. Outcomes for the intervention and control groups were compared using logistic regression, generalized linear models (GLMs) with a negative binomial distribution, ordinary least squares, and Cox proportional hazards regression.

Results

Compared to the control group (N = 1294), the intervention group (N = 1256) had a lower rate of all-cause rehospitalizations (62.6% vs. 66.4%, p = 0.05) and shorter lengths of stay (14.49 vs. 16.89 days, p = 0.02) during the 12-month follow-up period. These differences were also present for rehospitalizations due to the cardiac diseases qualifying for study recruitment, with rehospitalization rates for the intervention and control groups being 58.0% vs. 61.4% (p = 0.08) and particularly pronounced for lengths of rehospitalization stay of 12.97 vs. 15.40 days (p = 0.01), respectively. Subgroup analyses indicated positive effects of the intervention for patients 70 years and older (p = 0.05), females (p = 0.06), and those with little or no German language proficiency (p = 0.03). Furthermore, we found positive effects on patients’ adherence to health-related behavioral recommendations (81.91% vs. 73.95%, p = 0.000).

Conclusions

This study adds to the body of evidence indicating that care management interventions supporting patients as they transition from the inpatient to the outpatient sector can lower rehospitalizations, decrease length of rehospitalization stays, and improve adherence to post-discharge recommendations.

Trial registration

German Clinical Trial Register, DRKS00020424. Registered 2020-06-18. (retrospectively registered).
Heart-healthy diets including phytostanol ester consumption to reduce the risk of atherosclerotic cardiovascular diseases. A clinical review
Authors: Simonen Piia , Nylund Lotta , Vartiainen Erkki , Kovanen Petri T. , Strandberg Timo E. , Öörni Katariina , Wester Ingmar , Gylling Helena
Published: October 2024

The risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.e., low intakes of saturated and trans-fatty acids and cholesterol, and high intakes of unsaturated fatty acids, viscous fibre, and dietary phytostanols as fatty acid esters, according to international dyslipidaemia treatment guidelines. Calculations based on both FINRISK and Cholesterol Treatment Trialists’ Collaborators regression equations indicate that heart-healthy diets combined with phytostanol ester reduce LDL-C concentrations to such an extent that the 10-year estimated reduction in the incidence of coronary artery disease would be 23%. This information can be used, in particular, to prevent the development of subclinical atherosclerosis in healthy middle-aged populations and the progression of atherosclerosis to ASCVD. The outcome of simple and feasible dietary changes, and, when needed, combined with statins, can be significant: reduced mortality, an increased number of healthy life-years, and reduced healthcare costs.
The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering
Authors: Zhu Baiheng , Xiang Kehao , Li Tanghua , Li Xin , Shi Fujun
Published: October 2024

Breast cancer (BC) currently ranks second in the global cancer incidence rate. Hypoxia is a common phenomenon in BC. Under hypoxic conditions, cells in the tumor microenvironment (TME) secrete numerous extracellular vesicles (EVs) to achieve intercellular communication and alter the metabolism of primary and metastatic tumors that shape the TME. In addition, emerging studies have indicated that hypoxia can promote resistance to tumor treatment. Engineered EVs are expected to become carriers for cancer treatment due to their high biocompatibility, low immunogenicity, high drug delivery efficiency, and ease of modification. In this review, we summarize the mechanisms of EVs in the primary TME and distant metastasis of BC under hypoxic conditions. Additionally, we highlight the potential applications of engineered EVs in mitigating the malignant phenotypes of BC cells under hypoxia.
Current understanding of the impact of United States military airborne hazards and burn pit exposures on respiratory health
Authors: Trembley Janeen H. , Barach Paul , Tomáška Julie M. , Poole Jedidah T. , Ginex Pamela K. , Miller Robert F. , Lindheimer Jacob B. , Szema Anthony M. , Gandy Kimberly , Siddharthan Trishul , Kirkness Jason P. , Nixon Joshua P. , Torres Rosie Lopez , Klein Mark A. , Nurkiewicz Timothy R. , Butterick Tammy A.
Published: October 2024

Millions of United States (U.S.) troops deployed to the Middle East and Southwest Asia were exposed to toxic airborne hazards and/or open-air burn pits. Burn pit emissions contain particulate matter combined with toxic gasses and heavy metals. Ongoing research has demonstrated that exposures to the airborne hazards from military burn pits have profound and lasting health and wellness consequences. Research on the long-term health consequences of exposure to open burn pits has been limited. Work continues to understand the scope of the health impacts and the underlying pathobiology following exposures and to establish care standards. The U.S. Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act was signed into law August 2022. This act expands the benefits and services to U.S. Veterans exposed to toxicants, requires the Veterans Health Administration to provide toxic exposure screening, and supports increased research, education, and treatment due to toxic occupational exposures. This review highlights the state of the science related to military burn pit exposures research with an emphasis on pulmonary health. Clinical data demonstrate areas of reduced or delayed pulmonary ventilation and lung pathologies such as small airways scarring, diffuse collagen deposition and focal areas of ossification. Identification and characterization of foreign matter deposition in lung tissues are reported, including particulate matter, silica, titanium oxides, and polycyclic aromatic hydrocarbons. These data are consistent with toxic exposures and with the symptoms reported by post-deployment Veterans despite near-normal non-invasive pulmonary evaluations. On-going work toward new methods for non-invasive pulmonary diagnoses and disease monitoring are described. We propose various studies and databases as resources for clinical and health outcomes research. Pre-clinical research using different burn pit modeling approaches are summarized, including oropharyngeal aspiration, intranasal inhalation, and whole-body exposure chamber inhalation. These studies focus on the impacts of specific toxic substances as well as the effects of short-term and sustained insults over time on the pulmonary systems.
Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer’s disease
Authors: Taylor Xavier , Noristani Harun N. , Fitzgerald Griffin J. , Oluoch Herold , Babb Nick , McGathey Tyler , Carter Lindsay , Hole Justin T. , Lacor Pascale N. , DeMattos Ronald B. , Wang Yaming
Published: October 2024

Background

Anti-amyloid-β (Aβ) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aβ antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability. Nevertheless, further research is needed to understand the immediate downstream consequences of macrophage activation, potentially exacerbating CAA-related vascular permeability and microhemorrhages linked to Aβ immunotherapy.

Methods

This study investigates immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using RNA in situ hybridization, histology and digital spatial profiling in an Alzheimer's disease (AD) mouse model of microhemorrhage.

Results

In the present study, we have demonstrated that bapineuzumab murine surrogate (3D6) induces profound vascular damage, leading to smooth muscle cell loss and blood–brain barrier (BBB) breakdown. In addition, digital spatial profiling (DSP) reveals that distinct immune responses contribute to vascular damage with peripheral immune responses and perivascular macrophage activation linked to smooth muscle cell loss and vascular fibrosis, respectively. Finally, RNA in situ hybridization identifies two distinct subsets of Trem2+ macrophages representing tissue-resident and monocyte-derived macrophages around vascular amyloid deposits. Overall, these findings highlight multifaceted roles of immune activation and vascular damage in driving the development of microhemorrhage.

Conclusions

In summary, our study has established a significant link between CAA-Aβ antibody immune complex formation, immune activation and vascular damage leading to smooth muscle cell loss. However, the full implications of this cascade on the development of microhemorrhages requires further exploration. Additional investigations are warranted to unravel the precise molecular mechanisms leading to microhemorrhage, the interplay of diverse immune populations and the functional roles played by various Trem2+ macrophage populations in response to Aβ immunotherapy.
A review of the response and the emergency medical team (EMT) deployment following a tanker explosion in Freetown, Sierra Leone
Authors: Oyugi Boniface , Kamara Ibrahim Franklyn , Nuwagira Innocent , Musoke Robert , Lakoh Sulaiman , Jalloh Abdulai , Kamara Rashidatu Fouad , Relan Pryanka , Lajolo Camila , Ndiaye René André Macodou , Niang Babacar , Fall Mouhamadou Mansour , Balde Thierno , Salio Flavio , Kabba Mustapha
Published: October 2024

Background

On 5 November 2021, a fire incident following a tanker explosion occurred in the Wellington PMB Junction east of Freetown, Sierra Leone, injuring and killing people. WHO facilitated the deployment of international emergency medical teams (EMTs) to support the Ministry of Health (MoH) in providing care to the wounded in four hospitals.

Objective

In this study, we document Sierra Leone's experience managing the fire incident and the role of EMTs in responding to it.

Method

This is a cross-sectional After-Action Review (AAR) debrief of the response and deployment, including focus group discussion with WHO and MoH staff (n = 14) in a virtual workshop and document reviews on the response. The results thematically cover the event and the different agencies' responses and a review of EMTs' responses.

Results

At the onset of the emergency, the National Disaster Management Agency (NDMA) instituted a well-coordinated response mechanism in collaboration with the MoH and managed all response actions, such as medical services, informing partners and the public and coordinating all other agencies. WHO facilitated EMT deployments and mobilised medical supplies and equipment, while the MoH provided accommodation, logistics and coordination. The EMTs dispensed their functions with professionalism, adapted to the environment and available resources, and augmented the care the national health workers provided. They offered additional care: reconstructive surgery, pain management, palliative care, wound care, rehabilitation, physiotherapy and psychosocial counselling, which were initially inadequate at the onset of the disaster. 94 out of 157 patients were discharged home at the end. National clinicians acquired additional skills through the capacity-building activities of EMTs. The community appreciated the teams.

Conclusion

The government, partners and EMTs were important in the response and worked with speed and political acceptability using the context experience to provide surge support to the country. This experience brought to focus the idea of developing a national EMT in Sierra Leone, which would be useful to help respond even more swiftly. In collaboration with WHO, there is a need to institute further mechanisms to facilitate rapid response and quality-assured deployment of EMTs at regional and sub-regional levels and strengthen to support future responses.
High-cost users after sepsis: a population-based observational cohort study
Authors: Barrett Kali A. , Sheikh Fatima , Chechulina Victoria , Chung Hannah , Dodek Peter , Rosella Laura , Thavorn Kednapa , Scales Damon C. ,   Sepsis Canada
Published: October 2024

Background

High-cost users (HCU) represent important targets for health policy interventions. Sepsis is a life-threatening syndrome that is associated with high morbidity, mortality, and economic costs to the healthcare system. We sought to estimate the effect of sepsis on being a subsequent HCU.

Methods

Using linked health-administrative databases, we conducted a population-based, propensity score-weighted cohort study of adults who survived a hospitalization in Ontario, Canada between January 2016 and December 2017. Sepsis was identified using a validated algorithm. The primary outcome was being a persistent HCU after hospital discharge (in the top 5% or 1% of total health care spending for 90 consecutive days), and the proportion of follow-up time since discharge as a HCU.

Results

We identified 927,057 hospitalized individuals, of whom 79,065 had sepsis. Individuals who had sepsis were more likely to be a top 5% HCU for 90 consecutive days at any time after discharge compared to those without sepsis (OR 2.24; 95% confidence interval [CI] 2.04–2.46) and spent on average 42.3% of their follow up time as a top 5% HCU compared to 28.9% of time among those without sepsis (RR 1.46; 95% CI 1.45–1.48). Individuals with sepsis were more likely to be a top 1% HCU for 90 consecutive days compared to those without sepsis (10% versus 5.1%, OR 2.05 [95% CI 1.99–2.11]), and spent more time as a top 1% HCU (18.5% of time versus 10.8% of time, RR 1.68 [95% CI 1.65–1.70]).

Conclusions

The sequelae of sepsis result in higher healthcare costs with important economic implications. After discharge, individuals who experienced sepsis are more likely to be a HCU and spend more time as a HCU compared to individuals who did not experience sepsis during hospitalization.
Ribosomal S6 kinase (RSK) plays a critical role in DNA damage response via the phosphorylation of histone lysine demethylase KDM4B
Authors: Wu Wenwen , Zhu Jing , Nihira Naoe Taira , Togashi Yukiko , Goda Atsushi , Koike Junki , Yamaguchi Kiyoshi , Furukawa Yoichi , Tomita Takuya , Saeki Yasushi , Johmura Yoshikazu , Nakanishi Makoto , Miyoshi Yasuo , Ohta Tomohiko
Published: October 2024

Background

Epigenetic dysregulation affecting oncogenic transcription and DNA damage response is a hallmark of cancer. The histone demethylase KDM4B, a factor regulating these processes, plays important roles in estrogen receptor-mediated transcription and DNA repair in breast cancer. However, how oncogenic phospho-signal transduction affects epigenetic regulation is not fully understood. Here we found that KDM4B phosphorylation by ribosomal S6 kinase (RSK), a downstream effector of the Ras/MAPK pathway, is critical for the function of KDM4B in response to DNA damage.

Methods

KDM4B-knockout breast cancer cell lines were generated via CRISPR/Cas9-mediated gene editing. Re-expression of wild-type or phospho-site mutated KDM4B in knockout cells was performed by lentivirus-mediated gene transfer. Gene knockdown was achieved by RNA interference. DNA double-strand breaks (DSBs) were induced by ionizing radiation or laser-microirradiation. Protein accumulation at DSB sites was analyzed by immunofluorescence. KDM4B phosphorylation by RSK was assessed by in vitro and in vivo kinase assays. Gene and protein expression levels were analyzed by RT‒PCR and western blotting. The sensitivity of cells to ionizing radiation was examined by a clonogenic survival assay.

Results

RSK phosphorylated KDM4B at Ser666, and inhibition of the phosphorylation by RSK depletion or RSK inhibitors abrogated KDM4B accumulation at the sites of DNA double-strand breaks (DSBs). DSB repair was significantly delayed in KDM4B-knockout cells or cells treated with RSK inhibitors. The replacement of endogenous KDM4B with the phosphomimetic mutant S666D restored KDM4B accumulation and DSB repair that had been inhibited by RSK inhibitors, suggesting a critical role for RSK at the specific serine residue of KDM4B in the effect of RSK inhibitors on DSB repair. As a consequence of these aberrant responses, inhibition of KDM4B phosphorylation increased the sensitivity of the cells to ionizing radiation.

Conclusions

Overall, the present study uncovered a novel function of RSK on the DNA damage response, which provides an additional role of its inhibitor in cancer therapy.
Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation
Authors: van Vugt Marion , Finan Chris , Chopade Sandesh , Providencia Rui , Bezzina Connie R. , Asselbergs Folkert W. , van Setten Jessica , Schmidt A. Floriaan
Published: October 2024

Background

Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.

Methods

Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.

Results

We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.

Conclusions

This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.
Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial
Authors: Misset Benoît , Diep Anh Nguyet , Bertrand Axelle , Piagnerelli Michael , Hoste Eric , Michaux Isabelle , De Waele Elisabeth , Dumoulin Alexander , Jorens Philippe G. , van der Hauwaert Emmanuel , Vallot Frédéric , Swinnen Walter , De Schryver Nicolas , de Mey Nathalie , Layios Nathalie , Mesland Jean-Baptiste , Robinet Sébastien , Cavalier Etienne , Donneau Anne-Françoise , Moutschen Michel , Laterre Pierre-François
Published: October 2024

Background

Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP.

Methods

We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality.

Results

Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97).

Conclusion

In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes.

Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476.
The role of eco-anxiety in the presentation of bulimia nervosa: a case report
Authors: Runfola Cristin D. , Safer Debra L.
Published: October 2024

Background

Despite a growing literature demonstrating the significant impacts of climate change on mental health, research is urgently needed to investigate how climate change-related concerns may contribute to the development, exacerbation, or re-emergence of eating disorders, as well as affect the effectiveness of existing interventions. This case report contributes to this scant knowledge base by offering empirical evidence for how responses to climate change can influence eating disorder symptoms and, importantly, limit the effectiveness of evidence-based treatments such as Cognitive Behavior Therapy-Enhanced (CBT-E).

Case presentation

A 24-year-old female graduate student studying environmental science presented to a specialized eating disorder clinic with worsening bulimia nervosa. Her symptoms initially improved with CBT-E; however, after three months, concerns about food waste significantly impeded further progress. The therapist, identifying symptoms of eco-anxiety, adapted standard CBT-E strategies to include psychoeducation about eco-anxiety, cognitive restructuring of beliefs about food waste and other eating-related eco-concerns, relevant exposures related to such concerns, and problem-solving to increase social support. These adaptations led to resumed progress, with the patient achieving nutritional adequacy by treatment end (38 sessions) and maintaining treatment gains through one year follow-up.

Conclusions

To our awareness, this is the first case report on the co-occurrence of eco-anxiety and eating disorders. This case underscores the importance of screening for concurrent eco-anxiety, suggests ways in which eating disorders and eco-anxiety can influence one another longitudinally, describes how coexisting eco-anxiety can limit standard CBT-E’s effectiveness, and provides examples of successful treatment adaptations tailored to address eco-anxiety-related concerns.
Linear epitopes of PRRSV-1 envelope proteins ectodomains are not correlated with broad neutralization
Authors: Castillo-Pérez Jaime , Martínez-Lobo Francisco Javier , Frómeta Raquel , Castro José María , Simarro Isabel , Prieto Cinta
Published: October 2024

Background

Neutralizing antibodies against PRRSV are capable of conferring protection against viral reinfection, but they tend to be strain specific and usually have poor cross-reactivity. Nonetheless, it has been described that there are individuals capable of efficiently neutralizing viruses of different origin, so it is expected that there are conserved neutralizing epitopes relevant for broad neutralization. However, although immunodominant regions and neutralizing epitopes have been described in different envelope proteins, their role in broad neutralization is unknown. The main objective of this study was to determine whether the linear epitopes existing in the ectodomains of PRRSV envelope proteins play a role in cross-neutralization.

Results

A pepscan analysis was carried out using synthetic peptides against the ectodomains of PRRSV envelope proteins and PRRSV-hyperimmune sera of different cross-reactivity. The results obtained confirm the existence of antigenic regions in the ectodomains of the GP2, GP3, GP4 and GP5 that tend to be relatively conserved among different PRRSV isolates. Nonetheless, these antigenic regions have poor immunogenicity since they are only recognized by a limited number of sera. Furthermore, no differences were found between the reactivity of sera with broad cross-neutralization capacity and sera with poor heterologous neutralization activity, which indicate that linear epitopes existing in the ectodomains of PRRSV envelope proteins are not relevant for the development of broadly reactive neutralizing antibodies. Subsequently, some selected peptides were used in competition assays with the virus for binding to the cell receptors and in seroneutralization inhibition assays by incubation with hyperimmune sera. Firstly, some peptides that interfere with virus infectivity were identified in competition assays, but only in the case of one viral isolate, which points to the possible existence of a strain-dependent inhibition. However, the results of the seroneutralization inhibition assay indicate that, under the conditions of our study, none of the peptides used was capable of inhibiting virus neutralization by the hyperimmune sera.

Conclusions

The results obtained indicate that the linear peptides analyzed in this study do not play a major role in the induction of broadly reactive neutralizing antibodies, which could probably depend on conformational neutralizing.
Exploring in vivo and in vitro models for heart failure with biomarker insights: a review
Authors: Prajapati Anil Kumar , Shah Gaurang
Published: October 2024

Background

Heart failure (HF) is a condition characterized by the heart’s inability to meet the body’s demands, resulting in various complications. Two primary types of HF exist, namely HF with preserved left ventricular ejection fraction (LVEF) and HF reduced with LVEF. The progression of HF involves compensatory mechanisms such as cardiac hypertrophy, fibrosis, and alterations in gene expression. Pressure overload and volume overload are common etiologies of HF, with pressure overload often stemming from conditions like hypertension, leading to left ventricular hypertrophy and fibrosis. In contrast, volume overload can arise from chronic valvular regurgitant disease, also inducing left ventricular hypertrophy.

Main body

In vitro cell culture techniques serve as vital tools in studying HF pathophysiology, allowing researchers to investigate cellular responses and potential therapeutic targets. Additionally, biomarkers, measurable biological characteristics, play a crucial role in diagnosing and predicting HF. Some notable biomarkers include adrenomedullin, B-type natriuretic peptide, copeptin, galectin-3, interleukin-6, matrix metalloproteinases (MMPs), midregional pro-atrial natriuretic peptide, myostatin, procollagen type I C-terminal propeptide, procollagen type III N-terminal propeptide and tissue inhibitors of metalloproteinases (TIMPs). These biomarkers aid in HF diagnosis, assessing its severity, and monitoring treatment response, contributing to a deeper understanding of the disease and potentially leading to improved management strategies and outcomes.

Conclusions

This review provides comprehensive insights into various in vivo models of HF, commonly utilized cell lines in HF research, and pivotal biomarkers with diagnostic relevance for HF. By synthesizing this information, researchers gain valuable resources to further explore HF pathogenesis, identify novel therapeutic targets, and enhance diagnostic and prognostic approaches.
Toxicity Adaptive Lists Design: A Practical Design for Phase I Drug Combination Trials in Oncology
Authors: Russo Massimiliano , Mariani Francesco , Cleary James M. , Shapiro Geoffrey I. , Coté Gregory M. , Trippa Lorenzo
Published: October 2024

PURPOSE

We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations.

METHODS

Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data.

RESULTS

A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients.

CONCLUSION

The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations.
Technical Feasibility of Delineating the Thalamic Gustatory Tract Using Tractography
Authors: Sakakura Kazuki , Pertsch Nathan , Mueller Julia , Borghei Alireza , Rubert Nicholas , Sani Sepehr
Published: October 2024

BACKGROUND AND OBJECTIVES:

Magnetic resonance–guided focused ultrasound (MRgFUS) has been increasingly performed in recent years as a minimally invasive treatment of essential tremor and tremor-dominant Parkinson disease. One of the side effects after treatment is dysgeusia. Some centers use tractography to facilitate the treatment planning. However, there have been no reports of identifying gustatory tracts so far. Our aim was to investigate the technical feasibility of isolating and visualizing the gustatory tracts, as well as to explore the relationship between the gustatory tract and the MRgFUS lesion using actual patient data.

METHODS:

We used 20 randomly selected individuals from the Human Connectome Project database to perform tractography of the gustatory tracts. We defined region of interest as the dorsal region of the brainstem, Brodmann area 43 associated with taste perception, and a sphere with a 3-mm radius centered around the ventral intermediate nucleus in the anterior commissure-posterior commissure plane. We also examined the position of the gustatory tract in relation with other tracts, including the medial lemniscus, the pyramidal tract, and the dentatorubrothalamic tract. In addition, using the data of real patients with essential tremor, we investigated the distance between MRgFUS lesions and the gustatory tract and its association with the development of dysgeusia.

RESULTS:

We delineated a mean of 15 streamlines of the gustatory tracts per subject in each hemisphere. There was no statistical difference in the localization of the gustatory tracts between the left and right cerebral hemispheres. The gustatory tract was located anteromedial to the medial lemniscus and posteromedial to the dentatorubrothalamic tract in the anterior commissure-posterior commissure plane. The distance from the MRgFUS lesion to the gustatory tract was significantly shorter in the case where dysgeusia occurred compared with nondysgeusia cases (P-value: .0068).

CONCLUSION:

The thalamic gustatory tracts can be reliably visualized using tractography.
Glutaraldehyde-enhanced autofluorescence as a general tool for 3D morphological imaging
Authors: Niemeläinen Miika , Haapanen-Saaristo Anna-Mari , Koskinen Leena M. , Gullmets Josef , Peuhu Emilia , Meinander Annika , Calhim Sara , Paatero Ilkka
Published: October 2024

Routine histochemical techniques are capable of producing vast amount of information from diverse sample types, but these techniques are limited in their ability to generate 3D information. Autofluorescence imaging can be used to analyse samples in 3D but it suffers from weak/low signal intensities. Here, we describe a simple chemical treatment with glutaraldehyde to enhance autofluorescence for 3D fluorescence imaging and to generate detailed morphological images on whole-mount samples. This methodology is straightforward and cost-effective to implement, suitable for a wide range of organisms and sample types. Furthermore, it can be readily integrated with standard confocal and fluorescence microscopes for analysis. This approach has the potential to facilitate the analysis of biological 3D structures and research in developmental biology, including studies on model and non-model organisms.
40 years since the Heidelberg genetic screen that revolutionized developmental and cell biology
Authors: Peifer Mark
Published: October 2024

Our current understanding of the molecular basis of embryonic development and the shared machinery underlying this remarkable process has its roots in three papers published 40 years ago, which summarize the results of the Nobel Prize-winning ‘Heidelberg screen’. The genesis of these experiments that empowered us and the stories behind the experiments are worth revisiting.
Effects of hemodynamic load on cardiac remodeling in fish and mammals: the value of comparative models
Authors: Shaftoe Jared B. , Gillis Todd E.
Published: October 2024

The ability of the vertebrate heart to remodel enables the cardiac phenotype to be responsive to changes in physiological conditions and aerobic demand. Examples include exercise-induced cardiac hypertrophy, and the significant remodeling of the trout heart during thermal acclimation. Such changes are thought to occur in response to a change in hemodynamic load (i.e. the forces that the heart must work against to circulate blood). Variations in hemodynamic load are caused by either a volume overload (high volume of blood returning to the heart, impairing contraction) or a pressure overload (elevated afterload pressure that the heart must contract against). The changes observed in the heart during remodeling are regulated by multiple cellular signaling pathways. The cardiac response to these regulatory mechanisms occurs across levels of biological organization, affecting cardiac morphology, tissue composition and contractile function. Importantly, prolonged exposure to pressure overload can cause a physiological response – that improves function – to transition to a pathological response that causes loss of function. This Review explores the role of changes in hemodynamic load in regulating the remodeling response, and considers the cellular signals responsible for regulating remodeling, incorporating knowledge gained from studying biomedical models and comparative animal models. We specifically focus on the renin–angiotensin system, and the role of nitric oxide, oxygen free radicals and transforming growth factor beta. Through this approach, we highlight the strong conservation of the regulatory pathways of cardiac remodeling, and the specific conditions within endotherms that may be conducive to the development of pathological phenotypes.
Compras públicas na pandemia: experiências estaduais no federalismo bolsonarista
Authors: Tavares Rufino Filho Ednaldo , Simoni Júnior Sergio
Published: October 2024

O estudo teve como objetivo comparar as compras públicas realizadas pelos entes federativos estaduais em resposta à pandemia de Covid-19 nas áreas da saúde, educação e segurança pública. A base teórica para o artigo é a literatura sobre o federalismo brasileiro na pandemia. Foi realizada uma pesquisa de abordagem quantitativa dos dados com análise exploratória descritiva das compras públicas realizadas pelos 26 entes subnacionais estaduais nos anos de 2020 e 2021. Ao trazer os entes estaduais para o centro da análise, o estudo contribui com a recente literatura sobre o papel dos estados na produção de políticas públicas e no enfrentamento à emergência da Covid-19. A síntese dos resultados reforça a literatura recente ao indicar que a falta de coordenação nas políticas públicas resultou na heterogeneidade das compras públicas em resposta à Covid-19.
Transperto Transportes
Authors: Cernev Adrian Kemmer , Larieira Claudio , Santos Vanessa
Published: October 2024

A Transperto Transportes é uma empresa de pequeno porte que presta serviços de transporte de cargas leves na região metropolitana de São Paulo há mais de 15 anos. A empresa possui alguns softwares funcionando de forma isolada na operação do negócio, denotando um estágio ainda incipiente no uso de TI. Surgiu então a oportunidade de avançar na adoção e uso de tecnologias mais sofisticadas para gestão e suporte ao crescimento do negócio, incluindo um sistema integrado de informação. Seu fundador e principal gestor, Pedro Porto, recebeu uma proposta comercial e precisa agora decidir sobre a evolução tecnológica da empresa.
Rio de Janeiro, the Wonderful City, gets smarter, but for whom?
Authors: Lorenzo Manuela , Sá Bianca , Celano Ana
Published: October 2024

This teaching case illustrates a dilemma for Gabriel, a young man working as head of Rio de Janeiro’s urban planning secretary in early 2022. Gabriel built a successful career at Brazil’s most prominent technology company in the private sector. Still, a new challenge that was too big to refuse changed everything – now, starting in the public sector, Gabriel is responsible for a massive project that had the potential to change Rio de Janeiro’s downtown and make Rio a leading smart city. The project attracted significant attention from construction companies interested in the benefits they would gain with the contract. Moreover, Gabriel needed the project to be approved by the city council. He was confident about the project and that it was the change Rio’s downtown needed. But change for whom? A meeting with Teresa, a councilwoman critical of the project, unveiled the reality of the city center and its population to Gabriel. Teresa was an architect and urbanist, an activist for urban struggles, who had worked previously in urbanization and popular housing projects. Teresa shed light on the overlooked reality of the city: before being “smart,” Rio’s downtown needed social housing, culture, and security, in other words, basic needs. Now, Gabriel questioned which “change” Rio needed. Could Gabriel understand Rio’s needs with his private sector mindset? Or does he have to adopt a new mindset, the mindset of a public manager? Would the stakeholders still fund the project if he embraced Teresa’s perspective? What should Gabriel do?
Rank-and-File Employee Stock Options and Workplace Safety
Authors: Chen Yangyang , Ofosu Emmanuel , O’Sullivan Don , Veeraraghavan Madhu , Zolotoy Leon
Published: October 2024

We provide robust evidence that rank-and-file employee stock options (R&F options) lead to lower work-related injury rates. This finding is consistent with the view that R&F options improve workplace safety by facilitating employee retention and cooperation. To establish causality, we employ difference-in-differences analysis around the passage of FAS 123R option expensing regulation and instrumental variable estimation. In cross-sectional analysis, we find that the documented effect is amplified among firms with higher labor mobility rates and among firms with greater scope for employee free riding. The results of supplemental analysis suggest that work-related injuries adversely impact firm performance and rule out reduced employee whistleblowing about workplace safety issues as an alternative mechanism driving our findings.

This paper was accepted by Victoria Ivashina, finance.

Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2022.02072 .
CPD: Myopia management update part 2
Authors: Black Peter , Black Tina Arbon
Published: October 2024

Following on from their recent article Myopia management with spectacle lenses – an update (Optician July 28, 2023) – Peter Black and Tina Arbon Black explore myopia evidence, new management options and some of the standards of practice issues that surround myopia management
CPD: Making a big difference for little eyes 1
Authors: Gowing Jessica
Published: October 2024

In this first of two articles Jessica Gowing discusses two conditions that can affect paediatric facial and visual development
Sustainable product design
Authors: Emmins Sarah
Published: October 2024

Sarah Emmins considers the entire supply chain in whether something is sustainable or not
CPD: ‘Are you a driver?’: Communicating about fitness to drive in the eye examination
Authors: Rae Sheila
Published: October 2024

Dr Sheila Rae consider the visual acuity requirements for Group 1 drivers highlighting that drivers must achieve at least Snellen 6/12 acuity and pass the number plate test
Impact of storage on sterility of surgical instruments in autoclave bags
Authors: Hart Katherine , Cartlidge Helen
Published: October 2024

Background:

There is no published veterinary research to support an optimal storage duration and method of sterile surgical instrumentation (SI) when using self-seal autoclave bags (SSABs), although aspects of research from human healthcare are transferable. Multiple pieces of research in human healthcare have demonstrated the ability of sterilisation packaging materials to maintain barrier integrity and sterility for several months poststerilisation. Research on an optimal storage method is inconclusive.

Aims:

To determine an ideal storage duration and method of single SI, packaged in SSABs and sterilised via an autoclave. To determine the current practice of sterilisation, storage methods and durations using SSABs in small animal practice.

Methods:

This mixed methods study consisted of an online questionnaire to investigate the current procedures for autoclave sterilisation in veterinary practice. Alongside this, a non-randomised control study was conducted to assess the sterility of single SI, packaged in SSABs and sterilised via autoclave, to determine an ideal storage duration and method. SI was sterilised and stored for one, three and six months, in open (on a shelf) and closed (in a box) environments.

Results:

The questionnaire indicated veterinary professionals are adopting a cautious approach to storage durations with 75.5% (n=40) storing sterile single SI for between one and three months, prior to reprocessing. The experimental study did not identify an optimal storage method and either open or closed could be used for effective storage in undisturbed conditions. It is highly probable that most SI were sterile at the end of the storage durations and for up to 6 months.

Conclusions:

Laboratory findings are mostly consistent with those in existing literature. Results suggest the storage of sterile SI, in either open or closed environments for up to 6 months was not detrimental to the sterility of the instruments. To encourage good sustainability performance, practices could extend the storage times of sterilised SI prior to reprocessing.