Soil organic carbon (SOC), as the largest terrestrial carbon pool, plays an important role in global carbon (C) cycling, which may be significantly impacted by global changes such as nitrogen (N) ...fertilization, elevated carbon dioxide (CO2), warming, and increased precipitation. Yet, our ability to accurately detect and predict the impact of these global changes on SOC dynamics is still limited. Investigating SOC responses to global changes separately for mineral-associated organic carbon (MAOC) and the particulate organic carbon (POC) can aid in the understanding of overall SOC responses, because these are formed, protected, and lost through different pathways. To this end, we performed a systematic meta-analysis of the response of SOC, MAOC, and POC to global changes. POC was particularly responsive, confirming that it is a better diagnostic indicator of soil C changes in the short-term, compared to bulk SOC and MAOC. The effects of elevated CO2 and warming were subtle and evident only in the POC fraction (+5.11% and − 10.05%, respectively), while increased precipitation had no effects at all. Nitrogen fertilization, which comprised the majority of the dataset, increased SOC (+5.64%), MAOC (+4.49%), and POC (+13.17%). Effect size consistently varied with soil depth and experiment length, highlighting the importance of long-term experiments that sample the full soil profile in global change SOC studies. In addition, SOC pool responses to warming were modified by degree of warming, differently for air and soil warming manipulations. Overall, we suggest that MAOC and POC respond differently to global changes and moderators because of the different formation and loss processes that control these pools. Coupled with additional plant and microbial measurements, studying the individual responses of POC and MAOC improves understanding of the underlying dynamics of SOC responses to global change. This will help inform the role of SOC in mitigating the climate crisis.
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•Used meta-analysis to investigate soil carbon fractions responses to global change.•All soil organic carbon fractions increase under nitrogen fertilization.•Particulate organic carbon decreases with atmospheric warming.•Particulate organic carbon increases with elevated carbon dioxide.•Soil depth and experiment length were consistently important moderators.
Adolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and ...opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10-13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of psychosis-like experiences (PLE), internalizing symptoms, and externalizing symptoms. Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t = -2.69) and internalizing (t = -6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.
Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, ...may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births 95% confidence interval (CI) 216-263. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.
Squamous cell carcinomas are triggered by marked elevation of RAS-MAPK signalling and progression from benign papilloma to invasive malignancy
. At tumour-stromal interfaces, a subset of ...tumour-initiating progenitors, the cancer stem cells, obtain increased resistance to chemotherapy and immunotherapy along this pathway
. The distribution and changes in cancer stem cells during progression from a benign state to invasive squamous cell carcinoma remain unclear. Here we show in mice that, after oncogenic RAS activation, cancer stem cells rewire their gene expression program and trigger self-propelling, aberrant signalling crosstalk with their tissue microenvironment that drives their malignant progression. The non-genetic, dynamic cascade of intercellular exchanges involves downstream pathways that are often mutated in advanced metastatic squamous cell carcinomas with high mutational burden
. Coupling our clonal skin HRAS
mouse model with single-cell transcriptomics, chromatin landscaping, lentiviral reporters and lineage tracing, we show that aberrant crosstalk between cancer stem cells and their microenvironment triggers angiogenesis and TGFβ signalling, creating conditions that are conducive for hijacking leptin and leptin receptor signalling, which in turn launches downstream phosphoinositide 3-kinase (PI3K)-AKT-mTOR signalling during the benign-to-malignant transition. By functionally examining each step in this pathway, we reveal how dynamic temporal crosstalk with the microenvironment orchestrated by the stem cells profoundly fuels this path to malignancy. These insights suggest broad implications for cancer therapeutics.
Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we ...found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.
Through recurrent bouts synchronous with the hair cycle, quiescent melanocyte stem cells (McSCs) become activated to generate proliferative progeny that differentiate into pigment-producing ...melanocytes. The signaling factors orchestrating these events remain incompletely understood. Here, we use single-cell RNA sequencing with comparative gene expression analysis to elucidate the transcriptional dynamics of McSCs through quiescence, activation, and melanocyte maturation. Unearthing converging signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated. Employing conditional lineage-specific genetic ablation studies in mice, we found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation. We show that interestingly, BMP signaling functions downstream from activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, and chromatin landscaping, we show that following WNT-mediated activation of McSCs, BMP and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation. Our findings shed light upon the signaling interplay and timing of cues that orchestrate melanocyte lineage progression in the hair follicle and underscore a key role for BMP signaling in driving complete differentiation.
Abstract
Background
Motor abnormalities are strong transdiagnostic indicators of psychopathology risk that reflect emerging neural network abnormalities. Indeed, motor signs, such as motor slowing ...and agitation, are widely recognized as core features of both psychosis and depression. However, it is unclear whether these reflect shared or distinct etiology.
Methods
A sample of 11 878 adolescents completed self-reported clinical measures of rated psychotic-like experiences (PLEs) and depression. Familial risk for psychopathology and the presence of motor signs were drawn from parental reports, including developmental motor delays (eg, sitting, walking), and adolescent motor signs (eg, dyscoordination, psychomotor retardation, and psychomotor agitation). Finally, motor network connectivity in theoretically relevant networks (cortico-striatal, cortico-thalamic, and cortico-cerebellar) were related to symptoms and familial risk for psychopathology.
Results
Developmental motor delays related to increased PLEs, increased depression symptoms, and greater familial risk. Familial risk for both PLEs and depression showed higher rates of developmental motor delays than all other groups. Adolescent motor signs, however, showed unique patterns of relationships to symptoms and familial risk such that dyscoordination reflected risk for PLEs, both psychomotor agitation and retardation reflected depression risk, and psychomotor agitation reflected transdiagnostic risk. Cortico-striatal connectivity was related to depression and PLEs, but cortico-cerebellar connectivity was linked to PLEs only.
Conclusions
Motor signs may be a transdiagnostic marker of vulnerability for psychopathology. Early developmental motor delays could belie pluripotent, familial risk features. Unique items, eg, dyscoordination specifically related to PLEs, possibly reflecting processes inherent in distinct emerging forms of psychopathology.
Objectives
To determine the contribution of cognitive impairment, prefracture functional impairment, and treatment as predictors of functional status and mobility 6 months after discharge from ...rehabilitation for older adults with hip fracture.
Design
Longitudinal.
Setting
Inpatient rehabilitation units of two community hospitals.
Participants
Adults with hip fractures aged 65 and older who were discharged from a rehabilitation unit and had been living in the community before the fracture (N = 133).
Measurements
Mini‐Mental State Examination (MMSE) score at discharge from rehabilitation was used to identify the presence and severity of cognitive impairment. Outcomes were measured using questions from two subscales of the Functional Independence Measure (Self‐Care Function and Functional Mobility) and the New Mobility Scale (NMS). Measurements were made at discharge from a rehabilitation setting and 3 and 6 months after discharge.
Results
Prefracture functional impairment was associated with worse outcomes throughout the 6 months after discharge and with lower rates of improvement, or in some cases decline, after discharge. Cognitive impairment was associated with worse outcomes throughout the 6 months after discharge but was only weakly associated with lower rates of improvement or decline. The Patient Centered Rehabilitation Model of care targeting persons with cognitive impairment (PCRM‐CI) intervention group had higher NMS scores after discharge than a usual care group.
Conclusion
Although cognitive impairment and prefracture functional impairment contribute to poor outcomes, prefracture functional impairment was more strongly associated with poor outcomes than cognitive impairment. There is evidence to show that individuals with cognitive impairment are able to regain their mobility, which suggests a need for postdischarge targeted interventions that include a focus on activities of daily living for older adults with cognitive impairment and functional impairment to stabilize gains from inpatient rehabilitation.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many ...pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep. Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound. Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common. Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors.
Abstract
Background
Staff working in long-term care (LTC) homes during COVID-19 frequently reported a lack of communication, collaboration, and teamwork, all of which are associated with staff ...dissatisfaction, health concerns, lack of support and moral distress. Our study introduced regular huddles to support LTC staff during COVID-19, led by a Nurse Practitioner (NP). The objectives were to evaluate the process of huddle implementation and to examine differences in outcomes between categories of staff (direct care staff, allied care and support staff, and management) who attended huddles and those who did not.
Methods
All staff and management at one LTC home (< 150 beds) in Ontario, Canada were included in this pre-experimental design study. The process evaluation used a huddle observation tool and focused on the dose (duration, frequency) and fidelity (NP’s adherence to the huddle guide) of implementation. The staff attending and non-attending huddles were compared on outcomes measured at post-test: job satisfaction, physical and mental health, perception of support received, and levels of moral distress. The outcomes were assessed with validated measures and compared between categories of staff using Bayesian models.
Results
A total of 42 staff enrolled in the study (20 attending and 22 non-attending huddles). Forty-eight huddles were implemented by the NP over 15 weeks and lasted 15 min on average. Huddles were most commonly attended by direct care staff, followed by allied care/support, and management staff. All huddles adhered to the huddle guide as designed by the research team. Topics most often addressed during the huddles were related to resident care (46%) and staff well-being (34%). Differences were found between staff attending and non-attending huddles: direct care staff attending huddles reported lower levels of overall moral distress, and allied care and support staff attending huddles perceived higher levels of support from the NP.
Conclusions
NP-led huddles in LTC homes may positively influence staff outcomes. The process evaluation provided some understanding of why the huddles may have been beneficial: the NP addressed resident care issues which were important to staff, encouraged a collaborative approach to solving issues on the unit, and discussed their well-being.
Trial registration number
NCT05387213, registered on 24/05/2022.
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