Noise exposure during pregnancy may affect a child's auditory system, which may disturb fetal learning and language development. We examined the impact of occupational noise exposure during pregnancy ...on children's language acquisition at the age of one.
A cohort study was conducted among women working in the food industry, as kindergarten teachers, musicians, dental nurses, or pharmacists who had a child aged <1 year. The analyses covered 408 mother-child pairs. Language acquisition was measured using the Infant-Toddler Checklist. An occupational hygienist assessed noise exposure individually as no (N = 180), low (70-78 dB; N = 108) or moderate/high exposure (>79 dB; N = 120).
Among the boys, the adjusted mean differences in language acquisition scores were -0.4 (95% CI -2.5, 1.8) for low, and -0.7 (95% CI -2.9, 1.4) for moderate/high exposure compared to no exposure. Among the girls the respective scores were +0.1 (95% CI -2.2, 2.5) and -0.1 (95% CI -2.3, 2.2). Among the children of kindergarten teachers, who were mainly exposed to human noise, low or moderate exposure was associated with lower language acquisition scores. The adjusted mean differences were -3.8 (95% CI -7.2, -0.4) for low and -4.9 (95% CI -8.6, -1.2) for moderate exposure.
In general, we did not detect an association between maternal noise exposure and children's language acquisition among one-year-old children. However, the children of kindergarten teachers exposed to human noise had lower language acquisition scores than the children of the non-exposed participants. These suggestive findings merit further investigation by level and type of exposure.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the association between Wilms tumor histology at diagnosis and the change in Wilms' tumor volume during preoperative chemotherapy.
We included all the 52 patients operated for Wilms tumor ...at 1988–2015, who had both pathology samples and either CT or MRI-images before and after preoperative chemotherapy, available for reevaluation.
The median tumor volume was 586 ml (IQR 323–903) at diagnosis. The median change in tumor volume was −68% (IQR −85 to −40, p < 0.001) and the proportion of tumor necrosis 85% (IQR 24–97), after preoperative chemotherapy. There was a correlation between blastemal cell content in prechemotherapy cutting needle biopsy (CNB) sample and the reduction in tumor volume (Rho = −0.452, p = 0.002). High stromal and epithelial cell contents in CNB samples were associated with the lesser change in tumor volume (Rho = 0.279, p =0.053 and Rho = 0.300, p = 0.038 respectively). Reduction of tumor volume and the proportion of tumor necrosis after chemotherapy were associated (Rho = −0.502, p < 0.001). The actual viable tumor volume decreased in median by 97% (IQR 65–100), and the decrease could be seen in all cellular components. In three patients, the tumor volume increased more than 10% during the preoperative chemotherapy. Two of them had anaplastic tumor in the nephrectomy specimen.
Wilms tumor total and viable tumor volumes were reduced by 68% and 97% with preoperative chemotherapy, respectively. High proportion of blastemal cells in CNB was associated with greatest decrease in Wilms tumor volume. Increase in tumor volume during preoperative chemotherapy may indicate anaplastic tumor and prolonging of preoperative therapy should be avoided.
Retrospective review.
Level III.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To evaluate usefulness of cutting needle biopsy (CNB) to recognize pediatric renal tumors and to predict the evolution of histology during preoperative chemotherapy of Wilms tumors.
Ninety pediatric ...patients were operated for renal tumors at our institution in 1988–2015. We included all 64 patients who had undergone CNB at diagnosis and whose CNB and nephrectomy samples were available for re-evaluation.
The CNB was diagnostic in all 59 Wilms tumors but only in two out of five non-Wilms tumors. Anaplasia was missed by CNB in one of three with diffuse anaplasia in nephrectomy specimens. In Wilms tumors the proportions of the blastemal, stromal and epithelial components were 55% (IQR 25–85), 28% (IQR 10–58) and 2% (IQR 0–10) in CNB samples and 5% (IQR 0–64), 15% (IQR 0–50) and 15% (IQR 0–44) in the nephrectomy specimens (p-values 0.002, 0.599 and 0.005 respectively). The degree of tumor necrosis was in median 80% (IQR 21–97), after preoperative chemotherapy. The degree of tumor necrosis after chemotherapy had a positive correlation with the proportion of blastemal component (p=0.008) and a negative correlation with proportion of epithelial component in pre-chemotherapy CNB samples (p<0.001).
Wilms tumors are usually recognizable unlike non-Wilms tumors in CNB at diagnosis. In Wilms tumors, high blastemal cell content is associated with significant tumor necrosis during pre-operative chemotherapy. Our results do not support routine use of CNB in diagnosis of renal tumors.
Retrospective review.
Level III.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In view of the issues of low efficiency and environmental pollution existing in current antimony production, this work proposes an innovative and cleaner process to extract antimony from stibnite ...concentrate and co-treat goethite residues. The mechanisms of antimony extraction and zinc, iron, sulfur conservation was thermodynamically and experimentally investigated. The results show that iron- and zinc-bearing components in the goethite residue firstly reacted and releasing FexOy and ZnO, then stibnite (Sb2S3) quickly converted to senarmontite (Sb2O3) in the presence of FexOy and ZnO. Intermediate Sb2O3 was subsequently reduced to metallic Sb. Bench-scale experiments of antimony extraction from stibnite concentrate with goethite residue as sulfur-fixing agent validated that 85.7% of Sb was directly recovered as crude antimony bullion, only around 7.4% antimony volatilized to fume. Pb, As, Au, and Ag tended to also be co-enriched in the bullion. 97.4% of sulfur, 88.8% of zinc and 86.1% of iron were recovered and fixed simultaneously. Sulfur in Sb2S3, iron and zinc contained in goethite residues was conserved in matte as marketable Fe2Zn3S5, FeS, and ZnS, instead of forming gaseous SO2. This novel process is a promising recycling and co-treatment alternative for various secondary iron- and zinc-containing materials.
Phase conversion and evolution mechanism of antimony extraction and iron, zinc, sulfur conservation from stibnite concentrate and goethite residue. Display omitted
•A novel process was proposed to extract Sb from Sb2S3 and co-treat goethite residue.•The goethite residue firstly reacted releasing FexOy and ZnO.•Sb was extracted through the sequence of Sb2S3→FexOy/ZnO FeS/ZnS + Sb2O3→C/CO Sb.•85.7% of Sb can be extracted with 97.4% of S and 88.8% of Zn were recovered.•Pb, As, Au, Ag were co-enriched in the Sb bullion with Cu recovered mainly in matte.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In electrolytic production of zinc, the iron levels in the solutions are controlled by precipitation of jarosite or goethite. These precipitates also co-precipitate unrecovered valuable metals (Zn, ...Pb, Cu, Ag) as well as elements of concern (As, Cd, Hg). After stabilization, the residues are traditionally landfilled. This work investigates pyrometallurgical treatment of jarosite residue to convert the material into reusable clean slag and to recover the valuable metals within the residue. The pyrometallurgical treatment is divided into two functional steps. First, the material is melted in an oxidizing atmosphere, after which the oxide melt is reduced to produce an inert, clean slag. Then, a liquid metal or speiss phase collects the valuable metals, such as silver. The aim was to examine the optimal process conditions for reaching the target values for remaining metals in the slag; Pb < 0.03 wt %, Zn < 1 wt %. As a conclusion, the limiting factor in sulfur, lead, and zinc removal is the contact between the oxidizing or reducing gas and the molten sample. The mass transfer and volatile metals removal were significantly improved with a gas lance installation. The improved gas-liquid interaction enabled the first steps of gas flow rate optimization and ensured the sufficiently low end-concentrations of the aforementioned elements.
Abstract
Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various ...conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT (
p
< 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT (
p
< 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT (
p
< 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased (
p
< 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.
Purpose
Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, ...lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.
Methods
We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).
Results
Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2–28 years). The conditioning regimens for the final transplants were myeloablative (
n
= 20), reduced intensity (
n
= 8), or non-myeloablative (
n
= 2). Donors were HLA-matched related (
n
= 4), HLA-matched unrelated (
n
= 16), HLA-haploidentical (
n
= 2), or HLA-mismatched unrelated (
n
= 8). After a median follow-up of 2 years (range: 0.5–16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT.
Conclusion
HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency.
Clinical Implications
HCT is a definitive cure for DADA2 with > 95% survival.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel ...disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab.
An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine.
We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic lung problems are a rare but serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). We studied clinical phenotypes and polysomnography appearance of breathing ...abnormality in late onset non-infectious pulmonary complications (NIPS).
We reviewed Finnish national reference database between the years 1999 and 2016. We identified 12 children with most severely decreased pulmonary function and performed polysomnography and 24 aged-matched controls out of 325 performed pediatric allogeneic HSCTs.
All patients with NIPS had severely decreased pulmonary function already at 6 months post HSCT with median FEV
value 42% (interquartile range (IQR) 30-52%) of predicted normal values. Seven children had obstructive and five children more restrictive lung function. Children with obstructive lung function showed laborious breathing (7/7), decreased oxygenation and ventilation-to-perfusion mismatch (6/7), or REM-sleep-related hypoventilation (4/7) on polysomnography. Children with restrictive lung function (5/12) did not show sleep-related breathing disorder.
Children going through allogeneic HSCT who develop severe chronic obstructive lung function are more likely to present with sleep-related hypoxia and hypoventilation than children with restrictive lung function.
Children with severe obstructive lung function and chronic lung graft-versus-host disease following hematopoietic stem cell transplantation are more likely to present with sleep-related mild hypoxia and hypoventilation than children with restrictive lung disease. To our knowledge there are no reports on sleep-related breathing disorders and ventilatory function measured by polysomnography in children with pulmonary complications after allogeneic HSCT. Polysomnography may add to the differential diagnostics between patients with BOS and other non-infectious pulmonary complications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nicotinamide adenine dinucleotide (NAD
) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in ...mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)-discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD
metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD
metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.
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