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Allogeneic haematopoietic stem cell transplantation (alloHSCT) is safe and effective for adolescents and adults with inborn errors of immunity (IEI) with severe disease manifestations of their disease. The haematopoietic cell transplantation comorbidity index (HCT-CI) score predicts transplant survival in non-malignant diseases, including IEIs. We hypothesised that immune dysregulation pre-transplant may also influence transplant outcomes. We calculated the pre-transplant immune dysregulation and disease activity score (IDDA v2.1) for 82 adolescent and adult IEI patients (aged ≥ 13 years). Three-year overall survival (OS) for the whole cohort was 90% (n = 82) with a median follow up of 44.7 months (range 8.4 to 225.8). Events were defined as acute graft-versus-host disease (GvHD) grades II or above, chronic GvHD of any grade, graft failure, or death from any cause. Three-year event free survival (EFS) for the whole cohort was 72%. In multivariable analysis the IDDA v2.1 score pre-transplant and HCT-CI score significantly impacted OS (hazard ratio 1.08, p = 0.028) and EFS (hazard ratio 1.04, p = 0.0005). Importantly, 35% of this cohort had a high IDDA v2.1 score (≥ 15) and low HCT-CI score (< 3) suggesting that the risks of alloHSCT may be underestimated in a proportion of patients with IEI if the HCT-CI score is used alone. These findings support the potential for improved outcomes following successful modulation of immune dysregulation pre-transplant. The IDDA v2.1 score has utility as an objective measurement of pre-transplant immune dysregulation providing additional information reagrding the risks and potential complications of alloHSCT in an individual IEI patient., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

The application of organic amendments to contaminated soils is a remediation method to regulate metal(loid) leaching to waters and uptake to crops. Here, wood-derived biochar and/or green waste compost was amended to a Zn-rich agricultural soil (~ 450 mg kg -1 total Zn, derived from legacy sludge application). A pot experiment grew barley and pea crops in amended soil for 100 days, simultaneously measuring Zn, pH, and dissolved organic carbon (DOC) in pore waters and Zn uptake to plants. An assessment was made of leaching of Zn via a linked column test that recirculated soil leachates to amendments multiple times to chart the confounding impacts of pH and DOC on Zn mobility. Concentrations of Zn in pore waters in the pot test were reduced from 2 mg l -1 in soil without amendment to 1 mg l -1 following the addition of 5% (vol.) biochar and compost, which was reduced further (0.5 mg l -1 ) in the presence of crops. DOC appeared largely unaffected by soil amendment when mixed into soil, though was universally increased by the presence of the barley crop, whilst pH was variable (pH 4-6) and not clearly correlated with any intervention. Barley head mass was significantly increased after 5% biochar and both doses of compost amendment. Barley Zn content was maintained or enhanced by all soil amendments. The leaching column test revealed that biochar raised pH above that of the soil and compost amendment. Zn leachate concentrations were also reduced from after biochar amendment. Notably, compost resulted in net mobilisation of Zn from soil. This study demonstrates that the addition of biochar and compost to a Zn-rich agricultural soil was able to reduce pore water Zn considerably, especially in the presence of a barley crop. Compared to compost, biochar was the more efficient sorbent of Zn., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Allogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS., Methods: In this landmark analysis, 83 adults surviving 5 years or more following prior HSCT in childhood for IEI were recruited. The primary endpoint was event-free survival, defined as time post-first HSCT to graft failure, graft rejection, chronic infection, life-threatening or recurrent infections, malignancy, significant autoimmune disease, moderate to severe GVHD or major organ dysfunction. All events occurring less than 5 years post-HSCT were excluded., Results: EFS was 51% for the whole cohort at a median of 20 years post HSCT. Multivariable analysis identified age at transplant and whole blood chimerism as independent predictors of long-term EFS. Year of HSCT, donor, conditioning intensity and underlying diagnosis had no significant impact on EFS. 59 events occurring beyond 5 years post-HSCT were documented in 37 patients (45% cohort). A total of 25 patients (30% cohort) experienced ongoing significant complications requiring active medical intervention at last follow-up., Conclusion: Although most patients achieved excellent, durable immune reconstitution with infrequent transplant-related complications, very late complications are common and associated with mixed chimerism post-HSCT. Early intervention to correct mixed chimerism may improve long-term outcomes and adult health following HSCT for IEI in childhood., (© 2022. The Author(s).)

Neonicotinoid insecticides (NNIs) have been widely used to control insect pests, while their environmental residues and associated hazardous impacts on human and ecosystem health have attracted increasing attention worldwide. In this study, we examined the current levels and associated spatial and temporal patterns of NNIs in multiple environmental media across China. Concentrations of NNIs in surface water, sediment, and soil were in the range of 9.94-755 ng·L -1 , 0.07-8.30 ng·g -1 DW, and 0.009-356 ng·g -1 DW, respectively. The high levels of NNIs in surface water, such as in Yangtze River (755 ng·L -1 ), North River (539 ng·L -1 ), Nandu River (519 ng·L -1 ), and Minjiang River (514 ng·L -1 ), were dominated by imidacloprid, thiamethoxam, and acetamiprid due to their extensive use. The levels of NNIs in sediments were relatively low, and the highest concentration (8.30 ng·g -1 DW) was observed in Dongguan ditch. Sediment-water exchange calculated from fugacity fraction indicated that NNIs in sediment can be released back into the water due to their high solubility and low K OW . Soils from agricultural zones contained the largest residual NNIs, with imidacloprid concentrations in cultivated soil reaching 119 ng·g -1 DW. The calculated leaching potential showed that clothianidin has the highest migration potential to deep soil or groundwater. The monitored data of NNIs presented a decreasing trend from 2016 to 2018, which might be caused by the implementation of relevant control policies for NNI applications. The high levels of NNIs mainly occurred in southern China due to frequent agricultural activities and warm and humid meteorological conditions. The results from this study improve our understanding of the pollution levels and environmental behavior of NNIs in different environmental media across China and provide new knowledge that is needed for making future control policies for NNIs production and application., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor T H 17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.

Introduction: Disturbance to the hindgut microbiota can be detrimental to equine health. Metabolomics provides a robust approach to studying the functional aspect of hindgut microorganisms. Sample preparation is an important step towards achieving optimal results in the later stages of analysis. The preparation of samples is unique depending on the technique employed and the sample matrix to be analysed. Gas chromatography mass spectrometry (GCMS) is one of the most widely used platforms for the study of metabolomics and until now an optimised method has not been developed for equine faeces., Objectives: To compare a sample preparation method for extracting volatile organic compounds (VOCs) from equine faeces., Methods: Volatile organic compounds were determined by headspace solid phase microextraction gas chromatography mass spectrometry (HS-SPME-GCMS). Factors investigated were the mass of equine faeces, type of SPME fibre coating, vial volume and storage conditions., Results: The resultant method was unique to those developed for other species. Aliquots of 1000 or 2000 mg in 10 ml or 20 ml SPME headspace were optimal. From those tested, the extraction of VOCs should ideally be performed using a divinylbenzene-carboxen-polydimethysiloxane (DVB-CAR-PDMS) SPME fibre. Storage of faeces for up to 12 months at - 80 °C shared a greater percentage of VOCs with a fresh sample than the equivalent stored at - 20 °C., Conclusions: An optimised method for extracting VOCs from equine faeces using HS-SPME-GCMS has been developed and will act as a standard to enable comparisons between studies. This work has also highlighted storage conditions as an important factor to consider in experimental design for faecal metabolomics studies., Competing Interests: Compliance with ethical standardsRH, DA and CP declare that they have no conflict of interest.Ethical approval was granted by the University of Liverpool ethics committee (ref: VREC279). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Due to the need to increase understanding of factors associated with medication usage for youth with ADHD, this study examined parental explanatory etiologies in relationship to psychotropic medication use in a sample of youth who met criteria for ADHD and utilized outpatient specialty mental health services in the previous year. When examined cross-sectionally, medication usage was positively associated with parental explanatory etiologies related to physical causes and negatively associated with those involving sociological causes. Longitudinal analyses did not show a significant effect of Time 1 parental explanatory etiologies on the slope of medication use, suggesting that the relationship between Time 1 parental explanatory etiologies and medication usage remains stable over time for those who have had past year involvement with outpatient specialty mental health services.

The Federal government has promoted National Standards for Culturally and Linguistically Appropriate Services (CLAS) to reduce mental health disparities among Hispanic and Native American populations. In 2005, the State of New Mexico embarked upon a comprehensive reform of its behavioral health system with an emphasis on improving cultural competency. Using survey methods, we examine which language access services (i.e., capacity for bilingual care, interpretation, and translated written materials) and organizational supports (i.e., training, self-assessments of cultural competency, and collection of cultural data) mental health agencies in New Mexico had at the onset of a public sector mental health reform (Office of Minority Health 2001).

This study examined several hypotheses related to racial/ethnic variations in caregiver strain and perceived social support among parents caring for children with emotional/behavioral problems. A subsample of youth from the Patterns of Care (POC) study, which drew a stratified random sample of high-risk youth active to 1 of 5 public sectors of care, was used to test these hypotheses. When controlling for youth age, parental education, presence in an alcohol/drug or mental health (ADM) sector, and severity of child problems, African Americans reported significantly lower caregiver strain then did non-Hispanic Whites (NHWs), whereas Asian/Pacific Islanders (APIs) and Latinos did not differ significantly from NHWs. Contrary to prediction, both African Americans and APIs reported significantly lower perceived social support than NHWs, whereas Latinos did not differ significantly from NHWs. When perceived social support was controlled, the tendency of African American and API parents to report lower caregiver strain than NHWs became more pronounced. Thus, differences in perceived social support did not explain African Americans' lower caregiver strain. Other cultural variables such as familism and tolerance should be examined to identify processes that result in reduced perception of caregiver strain among African American parents caring for children with emotional/behavioral problems.

Racial/ethnic variations in clinical and service delivery characteristics among youth in public outpatient mental health services were examined using data from San Diego County mental health service programs for fiscal year 1996 to 1997 (N = 3,962). Differences in referral sources, primary diagnoses, and service types were investigated for three racial/ethnic groups (African Americans, Asian/Pacific Islander Americans, and Latinos) compared to non-Hispanic whites. Controlling for age, gender, functional impairment, and prior service use, significant differences by race/ethnicity were found for all three variables studied. Possible explanations for these variations and future directions for research are discussed.

Hypotheses generated by a developmental taxonomy that distinguishes between childhood and adolescent onset conduct disorders were tested. Hypotheses predicted that (1) individual and familial factors would be more strongly related to childhood onset conduct disorder, whereas ethnic minority status and exposure to deviant peers would be more strongly related to adolescent onset conduct disorder and (2) individuals with childhood onset disorder would be more likely to commit violent and victim oriented offenses than individuals with adolescent onset conduct disorder. The first hypothesis was strongly supported and the second hypothesis was partially supported. Implications for early identification of youth at risk for chronic offending are discussed.

Previous studies of childhood abuse levels among homeless women have typically focused either on single homeless women or female heads of families; almost none have focused specifically on homeless women with severe mental illness. This study explores rates of childhood physical and sexual abuse among 120 homeless women with severe mental illness. Correlates of experiencing childhood abuse are considered, including mental health outcomes and when women first become homeless. The prevalence of childhood abuse in this sample of women was substantially higher than among homeless women in general. The experience of childhood abuse was related to increased suicidality, and resulted in symptoms of posttraumatic stress disorder for some women. Women who had suffered abuse were also much more likely to become homeless during childhood and it is suggested that this is an important precursor to homelessness for many homeless women with chronic and severe mental illness.