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A hallmark of primary lymphoma of the central nervous system (CNS; PCNSL) is the strong CXCR4 expression of the tumor cells, the function of which is still unknown. In vitro treatment of BAL17CNS lymphoma cells by AMD3100, which inhibits CXCR4-CXCL12 interactions, resulted in the significantly differential expression of 273 genes encoding proteins involved in cell motility, cell-cell signaling and interaction, hematological system development and function, and immunologic disease. Among the genes down-regulated was the one encoding CD200, a regulator of CNS immunologic activity. These data directly translated into the in vivo situation; BAL17CNS CD200 expression was down-regulated by 89% (3% versus 28% CD200+ lymphoma cells) in AMD3100-treated versus untreated mice with BAL17CNS-induced PCNSL. Reduced lymphoma cell CD200 expression may contribute to the markedly increased microglial activation in AMD3100-treated mice. AMD3100 also maintained the structural integrity of blood-brain barrier tight junctions and the outer basal lamina of cerebral blood vessels. Subsequently, lymphoma cell invasion of the brain parenchyma was impaired, and maximal parenchymal tumor size was significantly reduced by 82% in the induction phase. Thus, AMD3100 qualified as a potentially attractive candidate to be included into the therapeutic concept of PCNSL. Beyond therapy, CXCR4-induced suppression of microglial activity is of general neuroimmunologic interest. This study identified CD200 expressed by the lymphoma cells as a novel mechanism of immune escape in PCNSL.
Subject(s)
Lymphoma , Receptors, CXCR4 , Mice , Animals , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Signal Transduction , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Benzylamines , Brain/metabolismABSTRACT
BACKGROUND: Opioid use disorder (OUD) care engagement rates in primary care (PC) settings are often low. Little is known about PC team experiences when delivering OUD treatment and potential factors that influence their capacity to engage patients in treatment. Exploring PC team experiences may inform needed supports that can optimize OUD care delivery and improve outcomes for patients with OUD. OBJECTIVE: We explored multidisciplinary PC team perspectives on barriers and facilitators to engaging patients in OUD treatment. DESIGN: Qualitative study using in-depth interviews. PARTICIPANTS: Primary care clinical teams. APPROACH: We conducted semi-structured interviews (n = 35) with PC team members involved in OUD care delivery, recruited using a combination of criterion and maximal variation sampling. Data collection and analysis were informed by existing theoretical literature about patient engagement, specifically that patient engagement is influenced by factors across individual (patient, provider), interpersonal (patient-provider), and health system domains. Interviews were professionally transcribed and doubled-coded using a coding schema based on the interview guide while allowing for emergent codes. Coding was iteratively reviewed using a constant comparison approach to identify themes and verified with participants and the full study team. KEY RESULTS: Analysis identified five themes that impact PC team ability to engage patients effectively, including limited patient contact (e.g., phone, text) in between visits, varying levels of provider confidence to navigate OUD treatment discussions, structural factors (e.g., schedules, productivity goals) that limited provider time, the role of team-based approaches in lessening discouragement and feelings of burnout, and lack of shared organizational vision for reducing harms from OUD. CONCLUSIONS: While the capacity of PC teams to engage patients in OUD care is influenced across multiple levels, some of the most promising opportunities may involve addressing system-level factors that limit PC team time and collaboration and promoting organizational alignment on goals for OUD treatment.
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BACKGROUND: Human scalp hair is a validated bio-substrate for monitoring various exposures in childhood including contextual stressors, environmental toxins, prescription or non-prescription drugs. Linear hair growth rates (HGR) are required to accurately interpret hair biomarker concentrations. METHODS: We measured HGR in a prospective cohort of preschool children (N = 266) aged 9-72 months and assessed demographic factors, anthropometrics, and hair protein content (HPC). We examined HGR differences by age, sex, race, height, hair pigment, and season, and used univariable and multivariable linear regression models to identify HGR-related factors. RESULTS: Infants below 1 year (288 ± 61 µm/day) had slower HGR than children aged 2-5 years (p = 0.0073). Dark-haired children (352 ± 52 µm/day) had higher HGR than light-haired children (325 ± 50 µm/day; p = 0.0019). Asian subjects had the highest HGR overall (p = 0.016). Younger children had higher HPC (p = 0.0014) and their HPC-adjusted HGRs were slower than older children (p = 0.0073). Age, height, hair pigmentation, and HPC were related to HGR in multivariable regression models. CONCLUSIONS: We identified age, height, hair pigment, and hair protein concentration as significant determinants of linear HGRs. These findings help explain the known hair biomarker differences between children and adults and aid accurate interpretation of hair biomarker results in preschool children. IMPACT: Discovery of hair biomarkers in the past few decades has transformed scientific disciplines like toxicology, pharmacology, epidemiology, forensics, healthcare, and developmental psychology. Identifying determinants of hair growth in children is essential for accurate interpretation of hair biomarker results in pediatric clinical studies. Childhood hair growth rates define the time-periods of biomarker incorporation into growing hair, essential for interpreting the biomarkers associated with environmental exposures and the mind-brain-body connectome. Our study describes age-, sex-, and height-based distributions of linear hair growth rates and provides determinants of linear hair growth rates in a large population of children. Age, height, hair pigmentation, and hair protein content are determinants of hair growth rates and should be accounted for in child hair biomarkers studies. Our findings on hair protein content and linear hair growth rates may provide physiological explanations for differences in hair growth rates and biomarkers in preschool children as compared to adults.
Subject(s)
Environmental Exposure , Hair , Infant , Adult , Humans , Child , Child, Preschool , Adolescent , Prospective Studies , Hair/chemistry , Biomarkers/analysis , AnthropometryABSTRACT
BACKGROUND: Studying transmission within the home is essential to understand the transmission dynamics of numerous infectious diseases. For Coronavirus Disease-2019 (COVID-19), transmission within the home constitutes the majority exposure context. The risk of infection in this setting can be quantified by the household/intra-family secondary attack rate (SAR). In the literature, there are discrepancies in these values and little information about its social determinants. The aim of this study was to investigate transmission in the home by analyzing the influence of occupational social class, country of origin and gender/sex. METHODS: This was a retrospective cohort study of a population registry of cohabiting contacts with COVID-19 cases diagnosed from 15 June to 23 December 2020, in the Murcia Region. The household SAR was analyzed considering the characteristics of the primary case (sex, age, symptoms, occupational social class, country of origin and number of people in the household) and contact (age and sex) using a multilevel binary logistic regression model. RESULTS: Among the 37 727 contacts included, the intra-family SAR was 39.1%. The contacts of confirmed primary cases in the migrant population (Africa and Latin America) had higher attack rates, even after adjusting for the other variables. Older age and female sex were independent risk factors for contracting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the home. CONCLUSION: There was greater intra-domiciliary transmission among immigrants, likely related to the conditions of the home and situation of social vulnerability. Women were more likely to be infected by transmission from a cohabiting infected individual.
Subject(s)
COVID-19 , SARS-CoV-2 , Social Determinants of Health , Humans , COVID-19/transmission , COVID-19/epidemiology , Male , Female , Adult , Retrospective Studies , Middle Aged , Risk Factors , Adolescent , Family Characteristics , Aged , Young Adult , Sex Factors , Child , Spain/epidemiology , Child, PreschoolABSTRACT
Megaconial congenital muscular dystrophy (MCMD) is a rare autosomal-recessive multisystem disorder characterized by delayed motor development, intellectual disability, and skin involvement. We report a patient with MCMD who had diffuse ichthyosis-like scaling, and successfully responded to ustekinumab.
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PURPOSE: Fifty percent of cranial CT scans performed achieve no benefit and entail risks. Our aim is to determine the yield of non-traumatic urgent cranial-CT and develop a pretest clinical probability scale approach. METHODS: Adult patients seen in our emergency department between 2017-2021 and referred for urgent cranial-CT for non-traumatic reasons were retrospectively recruited and randomly selected. Presenting complaint (PC), demographic variables, Relevant radiological findings (RRF) on the urgent cranial-CT and Relevant clinical-radiological findings (RCRF: admission need or RRF detection on the urgent cranial-CT or cranial CT/MRI in the following three months) were recruited. RESULTS: We recruited 702 patients, with median age 62 [47-76] years, 363 (51.7%) females. RCRF were observed in 404 (57.55%); of these, 352 (50.1%) required admission. RRF were detected in 190 (27.06%): 36 acute ischemic and 27 acute hemorrhagic lesions, 115 masses, 9 edema, and 27 hydrocephalus. Predictive PC for urgent cranial-CT were motor, speech, sensory deficits, sudden alteration of mental status, epileptic seizure, cognitive impairment, neurological symptoms in cancer patients, acute headache without a prior history and with meningeal signs; nausea, vomiting, or hypertensive crisis; visual deficits, and dizziness. This algorithm provided sensitivity, specificity, positive predictive value, and negative predictive value (NPV, 95%CI in brackets) of 92.1% (89-94.5%), 27.5% (22.5-33.0%), 63.3% (59.2-67.2%), and 71.9% (62.7-80.0%), to diagnose RCRF, and 97.4% (93.4-99.1%), 21.3% (17.8-25.1%), 31.5% (27.7-35.4%), and 95.6% (90.1-98.6%), to diagnose RRF. In patients not requiring admission (n = 350), the NPV for RRF was 98.8% (93.6-100%); the negative likelihood ratio 0.08 (0.01-0.57), and sensitivity remained at 97.8% (82.2-99.9%). Applying it would have avoided performing 85/350 urgent cranial-CT (24.29%). To find one RRF, we would have gone from performing 7.8 (350/45) to 5.9 (265/45) CTs, failing to diagnose 1/45 (2.2%) RRF. CONCLUSIONS: This proposed clinical scale could potentially decrease 24% of urgent cranial-CT.
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Effective treatment for opioid use disorder (OUD) is available, but patient engagement is central to achieving care outcomes. We conducted a scoping review to describe patient and provider-reported strategies that may contribute to patient engagement in outpatient OUD care delivery. We searched PubMed and Scopus for articles reporting patient and/or provider experiences with outpatient OUD care delivery. Analysis included: (1) describing specific engagement strategies, (2) mapping strategies to patient-centered care domains, and (3) identifying themes that characterize the relationship between engagement and patient-centered care. Of 3,222 articles screened, 30 articles met inclusion criteria. Analysis identified 14 actionable strategies that facilitate patient engagement and map to all patient-centered care domains. Seven themes emerged that characterize interpersonal approaches to OUD care engagement. Interpersonal interactions between patients and providers play a pivotal role in encouraging engagement throughout OUD treatment. Future research is needed to further evaluate promising engagement strategies.
Subject(s)
Opioid-Related Disorders , Outpatients , Humans , Opioid-Related Disorders/drug therapy , Delivery of Health Care , Patient-Centered Care , Treatment Outcome , Analgesics, Opioid/therapeutic useABSTRACT
We study the binding mechanism of CO and CO2 in the porous spin-crossover compound Fe(pz)[Pt(CN)4] by combining neutron diffraction (ND), inelastic neutron scattering (INS) and density-functional theory (DFT) calculations. Two adsorption sites are identified, above the open-metal site and between the pyrazine rings. For CO adsorption, the guest molecules are parallel to the neighboring gas molecules and perpendicular to the pyrazine planes. For CO2, the molecules adsorbed on-top of the open-metal site are perpendicular to the pyrazine rings and those between the pyrazines are almost parallel to them. These configurations are consistent with the INS data, which are in good agreement with the computed generalized phonon density of states. The most relevant signatures of the binding occur in the spectral region around 100 cm-1 and 400 cm-1. The first peak blue-shifts for both CO and CO2 adsorption, while the second red-shifts for CO and remains nearly unchanged for CO2. These spectral changes depend both from steric effects and the nature of the interaction. The interpretation of the INS data as supported by the computed binding energy and the molecular orbital analysis are consistent with a physisorption mechanism for both gases. This work shows the strength of the combination of neutron techniques and DFT calculations to characterize in detail the gas adsorption mechanism in this type of materials.
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We used THz (terahertz) and INS (inelastic neutron scattering) spectroscopies to study the interaction between an endohedral noble gas atom and the C60 molecular cage. The THz absorption spectra of powdered A@C60 samples (A = Ar, Ne, Kr) were measured in the energy range from 0.6 to 75 meV for a series of temperatures between 5 and 300 K. The INS measurements were carried out at liquid helium temperature in the energy transfer range from 0.78 to 54.6 meV. The THz spectra are dominated by one line, between 7 and 12 meV, at low temperatures for three noble gas atoms studied. The line shifts to higher energy and broadens as the temperature is increased. Using a spherical oscillator model, with a temperature-independent parameterized potential function and an atom-displacement-induced dipole moment, we show that the change of the THz spectrum shape with temperature is caused by the anharmonicity of the potential function. We find good agreement between experimentally determined potential energy functions and functions calculated with Lennard-Jones additive pair-wise potentials with parameters taken from the work of Pang and Brisse, J. Chem. Phys. 97, 8562 (1993).
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Background: Examining opioid use profiles over time and related factors among young adults is crucial to informing prevention efforts. Objectives: This study analyzed baseline data (Fall 2018) and one-year follow-up data from a cohort of 2,975 US young adults (Mage=24.55, 42.1% male; 71.7% White; 11.4% Hispanic). Multinomial logistic regression was used to examine: 1) psychosocial correlates (i.e. adverse childhood experiences [ACEs], depressive symptoms, parental substance use) of lifetime opioid use (i.e. prescription use vs. nonuse, nonmedical prescription [NMPO] use, and heroin use, respectively); and 2) psychosocial correlates and baseline lifetime use in relation to past 6-month use at one-year follow-up (i.e. prescription use vs. nonuse and NMPO/heroin use, respectively). Results: At baseline, lifetime use prevalence was: 30.2% prescription, 9.7% NMPO, and 3.1% heroin; past 6-month use prevalence was: 7.6% prescription, 2.5% NMPO, and 0.9% heroin. Compared to prescription users, nonusers reported fewer ACEs and having parents more likely to use tobacco, but less likely alcohol; NMPO users did not differ; and heroin users reported more ACEs and having parents more likely to use cannabis but less likely alcohol. At one-year follow-up, past 6-month use prevalence was: 4.3% prescription, 1.3% NMPO, and 1.4% heroin; relative to prescription users, nonusers were less likely to report baseline lifetime opioid use and reported fewer ACEs, and NMPO/heroin users were less likely to report baseline prescription opioid use but more likely heroin use. Conclusions: Psychosocial factors differentially correlate with young adult opioid use profiles, and thus may inform targeted interventions addressing different use patterns and psychosocial risk factors.
Subject(s)
Heroin Dependence , Opioid-Related Disorders , Prescription Drug Misuse , Humans , Male , Young Adult , Female , Analgesics, Opioid/therapeutic use , Heroin , Heroin Dependence/epidemiology , Longitudinal Studies , Prescription Drug Misuse/psychology , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/psychologyABSTRACT
Water deficit constitutes a severe limitation to agricultural productivity. In the context of sustainable crop production, the potential of microbial biotechnology to increase plant drought tolerance and improve crop yields under adverse conditions is gaining relevance. This work aimed to compare the performance of Azospirillumargentinense strain Az19 to that of strain Az39, the most widely used for commercial inoculants, when inoculated in maize plants exposed to water deficit. For this purpose, greenhouse and field assays were conducted. In the greenhouse experiment, strain Az19 prevented the adverse effect of water deficit at V2 stage on maize growth. Moreover, the percentage of fertile plants and the ear weight decreased significantly under water deficits imposed at V2 and flowering in Az39-inoculated plants but not in Az19-inoculated plants. In the first field trial with the commercial maize hybrid DOW DS 515 PW, Az19-inoculated plants were those which better tolerated the water deficit imposed. In the second field trial, two maize genotypes with differential drought sensitivity (LP 29×LP 2542, sensitive; LP 882 (923)×LP 4703, tolerant) were tested. Higher tolerance to water deficit was detected in plants inoculated with A. argentinense Az19, with a noticeable effect on grain yield components in the sensitive genotype. Based on these results, we propose the use of A. argentinense Az19 for the formulation of more targeted Azospirillum-based inoculants, suitable for agroecological areas subjected to seasonal water deficits.
Subject(s)
Azospirillum , Water , Zea mays , Agriculture , Plant DevelopmentABSTRACT
OBJECTIVE: Rapid progression of COVID-19 pneumonia may put patients at risk of requiring ventilatory support, such as non-invasive mechanical ventilation or endotracheal intubation. Implementing tools that detect COVID-19 pneumonia can improve the patient's healthcare. We aim to evaluate the efficacy and efficiency of the artificial intelligence (AI) tool GE Healthcare's Thoracic Care Suite (featuring Lunit INSIGHT CXR, TCS) to predict the ventilatory support need based on pneumonic progression of COVID-19 on consecutive chest X-rays. METHODS: Outpatients with confirmed SARS-CoV-2 infection, with chest X-ray (CXR) findings probable or indeterminate for COVID-19 pneumonia, who required a second CXR due to unfavorable clinical course, were collected. The number of affected lung fields for the two CXRs was assessed using the AI tool. RESULTS: One hundred fourteen patients (57.4 ± 14.2 years, 65 -57%- men) were retrospectively collected. Fifteen (13.2%) required ventilatory support. Progression of pneumonic extension ≥ 0.5 lung fields per day compared to pneumonia onset, detected using the TCS tool, increased the risk of requiring ventilatory support by 4-fold. Analyzing the AI output required 26 seconds of radiological time. CONCLUSIONS: Applying the AI tool, Thoracic Care Suite, to CXR of patients with COVID-19 pneumonia allows us to anticipate ventilatory support requirements requiring less than half a minute.
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In neuron-specific ovalbumin-transgenic CKTAC mice, antigen-specific OT-I CD8 T cells home to the enteric nervous system, where they attack and destroy neurons of the myenteric and submucosal plexus. Clinically, experimental autoimmune enteric ganglionitis (EAEG) manifests with gastrointestinal dysmotility and rapidly progresses to lethal ileus. Although interferon-γ has been identified as capable of damaging neurons in EAEG, the role of perforin, Fas/FasL, and tumor necrosis factor-α (TNF-α) in this disease is still a matter of debate. Thus, CKTAC mice were adoptively transferred with either perforin-/- or wild-type OT-I CD8 T cells. In addition, CKTAC mice that had received wild-type OT-I CD8 T cells were treated by either anti-TNF-α or anti-FasL. Furthermore, wild-type OT-I CD8 T cells were adoptively transferred into CKTAC mice with neuron-specific deletion of Fas. Although neither inactivation of enteric neuronal Fas nor anti-FasL treatment improved the disease, the absence of perforin from OT-I CD8 T cells and anti-TNF-α treatment significantly ameliorated EAEG and prevented lethal ileus by rescue of enteric neurons. Thus, these experiments identify perforin and TNF-α as important in the pathogenesis of EAEG.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Enteric Nervous System/pathology , Inflammatory Bowel Diseases/pathology , Neurons/pathology , Perforin/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , CD8-Positive T-Lymphocytes/metabolism , Disease Models, Animal , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/metabolism , MiceABSTRACT
OBJECTIVES: Identifying early markers of poor prognosis of coronavirus disease 2019 (COVID-19) is mandatory. Our purpose is to analyze by chest radiography if rapid worsening of COVID-19 pneumonia in the initial days has predictive value for ventilatory support (VS) need. METHODS: Ambispective observational ethically approved study in COVID-19 pneumonia inpatients, validated in a second outpatient sample. Brixia score (BS) was applied to the first and second chest radiography required for suspected COVID-19 pneumonia to determine the predictive capacity of BS worsening for VS need. Intraclass correlation coefficient (ICC) was previously analyzed among three radiologists. Sensitivity, specificity, likelihood ratios, AUC, and odds ratio were calculated using ROC curves and binary logistic regression analysis. A value of p < .05 was considered statistically significant. RESULTS: A total of 120 inpatients (55 ± 14 years, 68 men) and 112 outpatients (56 ± 13 years, 61 men) were recruited. The average ICC of the BS was between 0.812 (95% confidence interval 0.745-0.878) and 0.906 (95% confidence interval 0.844-0.940). According to the multivariate analysis, a BS worsening per day > 1.3 points within 10 days of the onset of symptoms doubles the risk for requiring VS in inpatients and 5 times in outpatients (p < .001). The findings from the second chest radiography were always better predictors of VS requirement than those from the first one. CONCLUSION: The early radiological worsening of SARS-CoV-2 pneumonia after symptoms onset is a determining factor of the final prognosis. In elderly patients with some comorbidity and pneumonia, a 48-72-h follow-up radiograph is recommended. KEY POINTS: ⢠An early worsening on chest X-ray in patients with SARS-CoV-2 pneumonia is highly predictive of the need for ventilatory support. ⢠This radiological worsening rate can be easily assessed by comparing the first and the second chest X-ray. ⢠In elderly patients with some comorbidity and SARS-CoV-2 pneumonia, close early radiological follow-up is recommended.
Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Comorbidity , Female , Humans , Male , Prognosis , RadiographyABSTRACT
In this practice note, we document the progression of the Community Vaccine Collaborative (CVC), on which we first published in 2021. The CVC convened to address deep COVID-19-related disparities affecting the Black, Latine, immigrant/refugee, and lesbian, gay, bisexual, transgender, queer, (questioning), intersex, asexual, and (agender) (LGBTQIA+) communities. The COVID-19 pandemic is rooted in centuries of oppression and marginalization leading to inequities and required dedicated focus to support marginalized communities in times of crisis. The CVC comprises community members, community-based organizations, health care providers, researchers, health systems leaders, and public health practitioners (among others), all of whom are dedicated to promoting COVID-19 vaccine equity. As the pandemic shifts and changes, so too has our group, to remain relevant to community needs and priorities. This article details Year 2 of the CVC, focusing on how we have grown and sustained this unique partnership. We also share results from an evaluation of the CVC, documenting participation in the collaborative space and alignment with CVC core principles. Finally, we discuss next steps and implications for the CVC including our pivot from vaccines to community vitality as we expand and sustain our collaborative efforts to address the ongoing COVID-19 pandemic and intersecting public health crises.
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Myelin-specific CD8(+) T cells are thought to contribute to the pathogenesis of multiple sclerosis. Here we modeled this contribution in mice with CD8(+) T cells recognizing ovalbumin (OVA) expressed in oligodendrocytes (ODCs). Surprisingly, even very high numbers of activated OVA-reactive CD8(+) T cells failed to induce disease and were cleared from the immune system after antigen encounter in the central nervous system (CNS). Peripheral infection with OVA-expressing Listeria (Lm-OVA) enabled CD8(+) T cells to enter the CNS, leading to the deletion of OVA-specific clones after OVA recognition on ODCs. In contrast, intracerebral infection allowed OVA-reactive CD8(+) T cells to cause demyelinating disease. Thus, in response to infection, CD8(+) T cells also patrol the CNS. If the CNS itself is infected, they destroy ODCs upon cognate antigen recognition in pursuit of pathogen eradication. In the sterile brain, however, antigen recognition on ODCs results in their deletion, thereby maintaining tolerance.
Subject(s)
Autoimmunity , Brain/immunology , CD8-Positive T-Lymphocytes/immunology , Immune Tolerance , Oligodendroglia/immunology , Animals , Antibodies, Monoclonal/immunology , Apoptosis/immunology , Autoantigens/immunology , Brain/microbiology , Hematopoiesis/immunology , Integrin alpha4beta1/immunology , Listeria monocytogenes/immunology , Listeriosis/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oligodendroglia/metabolism , Oligodendroglia/transplantation , Ovalbumin/immunology , Stromal Cells/immunology , Stromal Cells/metabolism , Thymus Gland/cytology , Thymus Gland/immunology , fas Receptor/immunologyABSTRACT
An increasing prevalence of early childhood adversity has reached epidemic proportions, creating a public health crisis. Rather than focusing only on adverse childhood experiences (ACEs) as the main lens for understanding early childhood experiences, detailed assessments of a child's social ecology are required to assess "early life adversity." These should also include the role of positive experiences, social relationships, and resilience-promoting factors. Comprehensive assessments of a child's physical and social ecology not only require parent/caregiver surveys and clinical observations, but also include measurements of the child's physiology using biomarkers. We identify cortisol as a stress biomarker and posit that hair cortisol concentrations represent a summative and chronological record of children's exposure to adverse experiences and other contextual stressors. Future research should use a social-ecological approach to investigate the robust interactions among adverse conditions, protective factors, genetic and epigenetic influences, environmental exposures, and social policy, within the context of a child's developmental stages. These contribute to their physical health, psychiatric conditions, cognitive/executive, social, and psychological functions, lifestyle choices, and socioeconomic outcomes. Such studies must inform preventive measures, therapeutic interventions, advocacy efforts, social policy changes, and public awareness campaigns to address early life adversities and their enduring effects on human potential. IMPACT: Current research does not support the practice of using ACEs as the main lens for understanding early childhood experiences. The social ecology of early childhood provides a contextual framework for evaluating the long-term health consequences of early life adversity. Comprehensive assessments reinforced with physiological measures and/or selected biomarkers, such as hair cortisol concentrations to assess early life stress, may provide critical insights into the relationships between early adversity, stress axis regulation, and subsequent health outcomes.
Subject(s)
Adverse Childhood Experiences , Child Behavior , Child Development , Social Determinants of Health , Social Environment , Stress, Psychological/epidemiology , Adrenal Glands/metabolism , Adrenal Glands/physiopathology , Adverse Childhood Experiences/psychology , Age Factors , Biomarkers/metabolism , Child , Hair/metabolism , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Risk Assessment , Risk Factors , Stress, Psychological/metabolism , Stress, Psychological/psychologyABSTRACT
The interactions between atoms and molecules may be described by a potential energy function of the nuclear coordinates. Nonbonded interactions between neutral atoms or molecules are dominated by repulsive forces at a short range and attractive dispersion forces at a medium range. Experimental data on the detailed interaction potentials for nonbonded interatomic and intermolecular forces are scarce. Here, we use terahertz spectroscopy and inelastic neutron scattering to determine the potential energy function for the nonbonded interaction between single He atoms and encapsulating C60 fullerene cages in the helium endofullerenes 3He@C60 and 4He@C60, synthesized by molecular surgery techniques. The experimentally derived potential is compared to estimates from quantum chemistry calculations and from sums of empirical two-body potentials.
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AIM: Compare a pre-co-seasonal with a perennial schedule using an undiluted mixture of a depigmented-polymerized grass/Olea europaea immunotherapy (2,000 DPP/mL) in pediatric patients with rhinitis/rhinoconjunctivitis with or without controlled asthma. MATERIAL AND METHODS: Primary objective was to determine the non-superiority of a perennial compared to a pre-co-seasonal schedule by means of Paediatric/Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ/AdolRQLQ). Secondary objectives were Paediatric Asthma/Caregiver´s Quality of Life Questionnaire (PAQLQ/PACQLQ) Asthma Control Test (ACT), Visual Analogue Scale global assessment of allergic disease (VAS), use of resources and immunological response. All variables were compared during the pollen season (April-June) without (2015) and with (2016) immunotherapy. RESULTS: Forty patients were included in the study of which 29 patients were assigned to the perennial and 11 to the pre-co-seasonal schedule. During 2016 pollen season a significant improvement in the PRQLQ/AdolRQLQ, PAQLQ/AdolAQLQ, ACT and VAS score were observed both in perennial and pre-co-seasonal schedule group. No significant differences were seen between treatment schedules for PRQLQ/AdolRQLQ, PAQLQ/AdolAQLQ and ACT scores comparing both pollen seasons. A significant increase in sIgG4 and reduction in the number of rescue medications used and number of patients who needed visit to any specialist was observed in both treatment schedules during 2016 pollen season. No relevant differences were found in the safety profile of any treatment schedule. DISCUSSION: Treatment with undiluted mixture of a depigmented-polymerized Grass/Olea europaea allergen immunotherapy has proven to be effective both using a perennial and a pre-co-seasonal schedule and therefore suitable for polyallergic patients.
Subject(s)
Seasons , Adolescent , Allergens , Asthma/therapy , Child , Desensitization, Immunologic , Humans , Olea/immunology , Poaceae , Quality of Life , Rhinitis, Allergic, Seasonal/therapy , Treatment OutcomeABSTRACT
Hydrocarbon pollution is an increasing problem affecting soil ecosystems. However, some microorganisms can cope with these pollutants and even facilitate plant establishment and thus phytoremediation. Within soil, arbuscular mycorrhizal fungi (AMF) have developed several strategies to survive and flourish under adverse conditions. Among these is the hyphal healing mechanism (HHM), a process allowing hyphae to re-establish integrity after physical injury. This mechanism differs among species and genera of AMF. However, whether and to what extent hydrocarbon pollution impacts the HHM is unknown. Here, the HHM was monitored in vitro on two AMF strains, Rhizophagus irregularis MUCL 41833 and Gigaspora sp. MUCL 52331, under increasing concentrations of diesel (1, 2, and 5% v:v). The addition of diesel slowed-down the HHM in both fungi. On Gigaspora sp., this effect was limited and most hyphae were able to heal after injury. Conversely, all steps of healing were severely impaired in R. irregularis. That fungus reconnected the injured hyphae at a much lower frequency than the Gigaspora sp., instead investing its energy to link neighboring hyphae or roots, or developing new branches from uninjured hyphae.