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1.
Front Immunol ; 15: 1433785, 2024.
Article in English | MEDLINE | ID: mdl-39136029

ABSTRACT

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαß, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Humans , Graft vs Host Disease/immunology , Graft vs Host Disease/etiology , Child , Male , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Child, Preschool , Prospective Studies , Incidence , Bone Marrow Transplantation/adverse effects , Infant , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Immune Reconstitution , Acute Disease
2.
Inorg Chem ; 63(24): 11168-11175, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38842464

ABSTRACT

The coordination chemistry of the homo- and heterodipnictogen tetrahedrane complexes [{CpMo(CO)2}2(µ,η2:2-EE')] (E, E' = P, As, Sb) (A-F) toward Tl[BArF24] ([BArF24]- = [B(3,5-C6H3(CF3)2)4]-) was studied. Controlled by the used tetrahedranes A-F, and thus depending on the respective pnictogen atoms, the monomers [Tl(η2-A)][BArF24] ([A]Tl) and [Tl(η2-B)][BArF24] ([B]Tl), the double substituted [Tl(η1-C)2][BArF24] ([C]2Tl) or the even higher aggregated compounds [Tl2(η2-D)3(µ,η2:1-D)(µ,η1:1-D)][BArF24]2 ([D]5Tl2), [Tl2(η2-E)2(µ,η2:1-E)3] [BArF24]2 ([E]5Tl2) and [Tl2(η2-F)3(µ,η2:1-F)3][BArF24]2 ([F]6Tl2) were obtained. Utilization of [BArF24]- promises additional stabilization of TlI via η6-coordination of two of its aryl rings as found in compounds [A]Tl, [B]Tl and [C]2Tl. Within the series of reactivity of A-F, the heavier congeners D, E and F tend to form larger aggregates in which σ(E-E') bond contributions to the coordination behavior were observed. Interatomic distances suggest the presence of Tl···Tl interactions in [E]5Tl2 and [F]6Tl2. The features of the respective coordination compounds were studied in the solid-state as well as in solution. For the latter at least a partial dissociation of the assemblies in solution was indicated. The isolated solid-state aggregates are the first examples of heterodipnictogen units as ligands in self-assembled TlI-based coordination compounds.

3.
Sci Rep ; 14(1): 12972, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839980

ABSTRACT

Pyogenic liver abscesses (PLA) are life-threatening disorders and require immediate treatment, but structured evidence is sparse and treatment guidelines are not established. In a retrospective observational study of 221 adult PLA patients (mean age 63 years, 63% men) treated between 2013 and 2019 at the Leipzig University Medical Center, we characterized pathogen spectrum, clinical management and outcomes. Biliary malignancies (33%), cholelithiasis (23%) and ischemic biliary tract disease (16%) were most common causes of PLA. Comorbidities included malignancies (40%) and diabetes mellitus (35%). Abdominal ultrasound was the preferred initial imaging modality (58%). Enterobacterales (58%), enterococci (42%) and streptococci (18%) were identified as most frequent pathogens. 97% of patients were treated with antibiotics and 75% of patients underwent an invasive treatment procedure. The 30-day mortality was almost identical in patients with and without underlying malignancy (14.6% vs. 14.4%, p = 0.96), while the one-year outcome differed significantly (58.4% vs. 29.6%, p < 0.001). Positive blood cultures (OR 4.78, 95% CI 1.39 to 22.5, p = 0.023) and detection of Enterobacterales (OR 3.55, 95% CI 1.40 to 9.97, p = 0.010) were associated with increased 30-day-mortality. We conclude that ultrasound, extensive microbiologic diagnosis, adequate anti-infective therapy and early intervention are crucial for the management of PLA.


Subject(s)
Anti-Bacterial Agents , Liver Abscess, Pyogenic , Tertiary Care Centers , Humans , Liver Abscess, Pyogenic/microbiology , Liver Abscess, Pyogenic/therapy , Liver Abscess, Pyogenic/diagnosis , Male , Middle Aged , Female , Aged , Retrospective Studies , Germany/epidemiology , Anti-Bacterial Agents/therapeutic use , Treatment Outcome , Adult , Aged, 80 and over
4.
Adv Ther ; 41(7): 2845-2858, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38775925

ABSTRACT

INTRODUCTION: Vasomotor symptoms (VMS), the characteristic symptoms of menopausal transition, are often the primary reason women seek treatment. Current treatment options for VMS include fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist. This study aimed to define a clinically meaningful threshold for reduction of moderate-to-severe VMS in postmenopausal women treated with fezolinetant and then apply it in a responder analysis of the pooled trial data. METHODS: This analysis pooled data from two identical phase 3, double-blind, placebo-controlled studies that randomized women with moderate-to-severe VMS to once-daily fezolinetant 30 mg, 45 mg, or placebo (SKYLIGHT 1 and 2). The frequency of VMS was collected daily using an electronic diary. Patients completed the Patient Global Impression of Change in VMS (PGI-C VMS) instrument, which assessed changes in hot flushes/night sweats at weeks 4 and 12 compared with baseline using a seven-point Likert scale. VMS frequency data were anchored to PGI-C VMS data; the anchor level for meaningful within-patient change in PGI-C VMS was "moderately better." RESULTS: In the pooled population (N = 1022), the mean (standard deviation) estimated thresholds for a meaningful within-patient change in moderate-to-severe VMS frequency were - 5.73 (3.47) at week 4 and - 6.20 (5.18) at week 12. Applying the thresholds for meaningful within-patient change to responder analyses ("missing as non-responder" imputation method) indicated a favorable clinical benefit: greater proportions of responders were observed in the fezolinetant 30-mg and 45-mg groups compared with placebo at week 4 (odds ratio range 2.48-2.91; P < 0.001) and week 12 (odds ratio range 1.908-2.68; P < 0.001). CONCLUSION: PGI-C VMS is sensitive to change and correlates with VMS frequency: a reduction of approximately six VMS episodes per day from baseline to week 12 was meaningful at the individual patient level. Fezolinetant provides a meaningful clinical benefit for women with moderate-to-severe VMS associated with menopause and represents an important nonhormonal treatment option. TRIAL REGISTRATION NUMBER: NCT04003155 and NCT04003142.


Subject(s)
Hot Flashes , Humans , Female , Hot Flashes/drug therapy , Middle Aged , Double-Blind Method , Postmenopause , Aged , Treatment Outcome , Sweating/drug effects , Clinical Trials, Phase III as Topic
5.
Chem Commun (Camb) ; 60(35): 4703-4706, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38596847

ABSTRACT

The reaction of the tetrahedral complex [{CpMo(CO)2}2(µ,η2-AsSb)] with CuI and AgI salts is presented which gives unprecedented neutral and cationic supramolecular aggregates featuring mixed As/Sb-donor molecules as ligands/linkers between metal ions.

6.
Dalton Trans ; 52(48): 18137-18142, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38031896

ABSTRACT

The reaction of the Ag(I) dimer [Ag2(η2-A)2(µ,η1:η1-A)2][TEF]2 (A = [{CpMo(CO)2}2(µ,η2-P2)]) possessing labile η2-coordinated P2 ligands with the organometallic dipnictogen compounds [{CpMo(CO)2}2(µ,η2-EE')] (E = E' = As, Sb; E = P, E' = As, Sb) represents a facile synthetic route towards unprecedented heteroleptic pnictogen-rich supramolecular complexes. This method can also be extended to the analogous Cu(I) dimer and is studied by DFT computations.

7.
Environ Int ; 180: 108161, 2023 10.
Article in English | MEDLINE | ID: mdl-37758599

ABSTRACT

Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.


Subject(s)
Food Contamination , Noncommunicable Diseases , Humans , Food Contamination/analysis , Public Health , Food Packaging , Food , Hazardous Substances/toxicity
8.
Chem Commun (Camb) ; 59(75): 11192-11195, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37650148

ABSTRACT

The reaction of the low-coordinate quadruply-bonded dimolybdenum complex Mo2[µ,κ2-PhB(N-2,6-iPr2C6H3)2]2 (1) with Cp*Fe(η5-E5) (E = P, As) gives two trinuclear species Cp*Fe(µ3,η5:2:2-E5)Mo2[µ,κ2-PhB(N-2,6-iPr2C6H3)2]2 (E = P (4) and As (5)). 4 undergoes facile isomerisation upon heating to give Cp*FeMo2[κ2-PhB(N-2,6-iPr2C6H3)2](µ3,κ:κ:η2-P2)[µ3,κ:κ:η3κ-P3PhB(N-2,6-iPr2C6H3)2] (6), where the FeMo2P5 core motif displays a cubane-like structure.

10.
Chemistry ; 29(61): e202301974, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37493637

ABSTRACT

The reactivity of the mixed dipnictogen complexes [{CpMo(CO)2 }2 (µ,η2 : 2 -PE)] (E=P, As, Sb) towards different group 14 electrophiles is reported. The resulting library of cationic compounds [{CpMo(CO)2 }2 (µ,η2 : 2 -EPR)]+ (R=Mes (2,4,6-C6 H2 Me3 ), CH3 , CPh3 , SnMe3 ) represents formally inorganic diazonium homologs which are stabilized by transition metal units. Modifying the steric and electronic properties of the electrophile drastically impacts the respective P-R bond lengths and is accompanied by increasing (SnMe3 >CPh3 >CH3 ) dynamic behavior in solution. In contrast to the well-studied organic analogs, the prepared compounds are stable at room temperature. The subsequent reaction of the model substrate [{CpMo(CO)2 }2 (µ,η2 : 2 -P2 Me)][OTf] ([OTf]- =[CF3 SO3 ]- ) with different N-heterocyclic carbenes (NHCs) leads to an addition at the unsubstituted P atom which is also predicted by computational methods. NMR spectroscopy confirms the formation of two isomers sync/gauche-[{CpMo(CO)2 }(µ,η2 : 1 -P(NHC)PMe){CpMo(CO)2 }][OTf]. X-ray crystallographic characterization and additional DFT calculations shed light on the spatial arrangement as well as on the possible formation pathways of the isomers.

11.
Cardiol Ther ; 12(2): 371-391, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37138193

ABSTRACT

INTRODUCTION: Treatment adherence and persistence impact the effectiveness of edoxaban for the prevention of thromboembolism in patients with atrial fibrillation (AF). The objective of this analysis was to assess adherence and persistence of edoxaban vs. other non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). METHODS: Utilizing a German claims database, adults with AF with the first pharmacy claim identified for edoxaban, apixaban, dabigatran, rivaroxaban, or VKAs from January 2013 to December 2017 were included in a propensity score-matched analysis. The first pharmacy claim was the index claim. Adherence (i.e., proportion of days covered [PDC]) and persistence (proportion of patients who continued therapy) were compared between edoxaban and other therapies. Patients receiving once-daily (QD) vs. twice-daily (BID) NOAC were also analyzed. RESULTS: Overall, 21,038 patients were included (1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA). After matching, baseline characteristics were well balanced across cohorts. Adherence was significantly higher for edoxaban vs. apixaban, dabigatran, and VKAs (all P < 0.0001). Significantly more edoxaban patients continued therapy vs. rivaroxaban (P = 0.0153), dabigatran (P < 0.0001), and VKAs (P < 0.0001). Time to discontinuation was significantly longer for edoxaban vs. dabigatran, rivaroxaban, and VKAs (all P < 0.0001). More patients receiving NOACs QD had a PDC ≥ 0.8 compared with those receiving NOACs BID (65.3 vs. 49.6%, respectively; P < 0.05); persistence rates were comparable between QD and BID groups. CONCLUSIONS: Patients with AF receiving edoxaban had significantly higher adherence and persistence compared with those receiving VKAs. This trend was also seen in NOAC QD regimens vs. NOAC BID regimens for adherence. These results provide insight into how adherence and persistence may contribute to the effectiveness of edoxaban for stroke prevention in patients with AF in Germany.

12.
Chem Sci ; 14(18): 4769-4776, 2023 May 10.
Article in English | MEDLINE | ID: mdl-37181779

ABSTRACT

Insertion and functionalization of gallasilylenes [LPhSi-Ga(Cl)LBDI] (LPh = PhC(NtBu)2; LBDI = [{2,6-iPr2C6H3NCMe}2CH]) into the cyclo-E5 rings of [Cp*Fe(η5-E5)] (Cp* = η5-C5Me5; E = P, As) are reported. Reactions of [Cp*Fe(η5-E5)] with gallasilylene result in E-E/Si-Ga bond cleavage and the insertion of the silylene in the cyclo-E5 rings. [(LPhSi-Ga(Cl)LBDI){(η4-P5)FeCp*}], in which the Si atom binds to the bent cyclo-P5 ring, was identified as a reaction intermediate. The ring-expansion products are stable at room temperature, while isomerization occurred at higher temperature, and the silylene moiety further migrates to the Fe atom, forming the corresponding ring-construction isomers. Furthermore, reaction of [Cp*Fe(η5-As5)] with the heavier gallagermylene [LPhGe-Ga(Cl)LBDI] was also investigated. All the isolated complexes represent rare examples of mixed group 13/14 iron polypnictogenides, which could only be synthesized by taking advantage of the cooperativity of the gallatetrylenes featuring low-valent Si(ii) or Ge(ii) and Lewis acidic Ga(iii) units/entities.

13.
Chemistry ; 29(24): e202300340, 2023 Apr 25.
Article in English | MEDLINE | ID: mdl-36809680

ABSTRACT

A missing family of the extremely air sensitive tripentelyltrielanes was discovered. Their stabilisation was achieved by using the bulky NHC IDipp (NHC=N-heterocyclic carbene, IDipp=1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene). The tripentelylgallanes and tripentelylalanes IDipp ⋅ Ga(PH2 )3 (1 a), IDipp ⋅ Ga(AsH2 )3 (1 b), IDipp ⋅ Al(PH2 )3 (2 a) and IDipp ⋅ Al(AsH2 )3 (2 b) were synthesised by salt metathesis of IDipp ⋅ ECl3 (E=Al, Ga, In) with alkali metal pnictogenides such as NaPH2 /LiPH2 ⋅ DME and KAsH2 , respectively. Moreover, the detection of the first NHC-stabilised tripentelylindiumane IDipp ⋅ In(PH2 )3 (3) was possible by multinuclear NMR spectroscopy. Initial investigations of the coordination ability of these compounds resulted in the successful isolation of the coordination compound [IDipp ⋅ Ga(PH2 )2 (µ3 -PH2 {HgC6 F4 }3 )] (4) by reaction of 1 a with (HgC6 F4 )3 . The compounds were characterised by multinuclear NMR spectroscopy as well as single crystal X-ray diffraction studies. Supporting computational studies highlight the electronic features of the products.

14.
Crit Rev Food Sci Nutr ; 63(28): 9425-9435, 2023.
Article in English | MEDLINE | ID: mdl-35585831

ABSTRACT

Food packaging is important for today's globalized food system, but food contact materials (FCMs) can also be a source of hazardous chemicals migrating into foodstuffs. Assessing the impacts of FCMs on human health requires a comprehensive identification of the chemicals they contain, the food contact chemicals (FCCs). We systematically compiled the "database on migrating and extractable food contact chemicals" (FCCmigex) using information from 1210 studies. We found that to date 2881 FCCs have been detected, in a total of six FCM groups (Plastics, Paper & Board, Metal, Multi-materials, Glass & Ceramic, and Other FCMs). 65% of these detected FCCs were previously not known to be used in FCMs. Conversely, of the more than 12'000 FCCs known to be used, only 1013 are included in the FCCmigex database. Plastic is the most studied FCM with 1975 FCCs detected. Our findings expand the universe of known FCCs to 14,153 chemicals. This knowledge contributes to developing non-hazardous FCMs that lead to safer food and support a circular economy.


Subject(s)
Food Contamination , Food Packaging , Humans , Food Contamination/analysis , Hazardous Substances/analysis , Databases, Factual , Plastics
15.
Sci Rep ; 12(1): 16788, 2022 10 06.
Article in English | MEDLINE | ID: mdl-36202937

ABSTRACT

The resistance of hard corals to warming can be negatively affected by nitrate eutrophication, but related knowledge for soft corals is scarce. We thus investigated the ecophysiological response of the pulsating soft coral Xenia umbellata to different levels of nitrate eutrophication (control = 0.6, medium = 6, high = 37 µM nitrate) in a laboratory experiment, with additional warming (27.7 to 32.8 °C) from days 17 to 37. High nitrate eutrophication enhanced cellular chlorophyll a content of Symbiodiniaceae by 168%, while it reduced gross photosynthesis by 56%. After additional warming, polyp pulsation rate was reduced by 100% in both nitrate eutrophication treatments, and additional polyp loss of 7% d-1 and total fragment mortality of 26% was observed in the high nitrate eutrophication treatment. Warming alone did not affect any of the investigated response parameters. These results suggest that X. umbellata exhibits resistance to warming, which may facilitate ecological dominance over some hard corals as ocean temperatures warm, though a clear negative physiological response occurs when combined with nitrate eutrophication. This study thus confirms the importance of investigating combinations of global and local factors to understand and manage changing coral reefs.


Subject(s)
Anthozoa , Dinoflagellida , Animals , Anthozoa/physiology , Chlorophyll A , Coral Reefs , Nitrates , Organic Chemicals
16.
J Hazard Mater ; 437: 129167, 2022 09 05.
Article in English | MEDLINE | ID: mdl-35897167

ABSTRACT

The EU Chemicals Strategy for Sustainability (CSS) aims at removing the most harmful chemicals from consumer products, including from food contact materials (FCMs). If implemented as intended, the CSS has the potential to significantly improve the protection of public health by banning the use of chemicals of concern that are carcinogenic, mutagenic, or toxic to reproduction (CMRs), or persistent and bioaccumulative, or endocrine-disrupting chemicals (EDCs) in FCMs. However, until now an overview of such food contact chemicals of concern (FCCoCs) has not been available, because the CSS is fairly recent. Therefore, we here systematically analyze the food contact chemicals listed for intentional use in FCMs and identify known FCCoCs. We present a list of 388 FCCoCs that should be phased-out from use. Of these, 352 are CMRs, four are per- and polyfluoroalkyl substances (PFAS), and 127 have empirical evidence for presence in FCMs. Importantly, 30 FCCoCs with evidence for presence are monomers of which 22 have evidence for migration into foodstuff showing that monomers in FCMs indeed become relevant for human exposure. Our findings justify moving away from a risk- towards a hazard-based approach to regulation of chemicals in FCMs.


Subject(s)
Dietary Exposure/statistics & numerical data , Food Contamination , Hazardous Substances , Endocrine Disruptors/analysis , Endocrine Disruptors/toxicity , European Union , Food , Food Packaging , Humans , Persistent Organic Pollutants , Public Health , Reproduction
17.
Environ Sci Technol ; 56(4): 2487-2496, 2022 02 15.
Article in English | MEDLINE | ID: mdl-35080176

ABSTRACT

Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism-disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized the chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, the chemicals extracted from one-third of the products caused murine 3T3-L1 preadipocytes to proliferate, and differentiate into adipocytes, which were larger and contained more triglycerides than those treated with the reference compound rosiglitazone. Because the majority of plastic extracts did not activate the peroxisome proliferator-activated receptor γ and the glucocorticoid receptor, the adipogenic effects are mediated via other mechanisms and, thus, likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.


Subject(s)
Adipogenesis , Plastics , 3T3-L1 Cells , Adipocytes , Animals , Mice , Obesity , PPAR gamma , Plastics/pharmacology
18.
J AOAC Int ; 105(2): 442-455, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-34791280

ABSTRACT

BACKGROUND: According to Codex Alimentarius, food products containing less than 20 mg/kg gluten can be labeled as "gluten-free." Since 2002, the R5 antibody method allowed determination of gluten levels and led to a huge improvement of products available to celiac disease (CD) patients. METHOD: The R5-containing test kit RIDASCREEN® Gliadin in combination with the cocktail solution was endorsed as Codex Type 1 Method in 2006 based on a collaborative study with corn-based bread, rice-based dough, wheat starches, rice, and corn flour. In 2012, the method was approved as First Action Official MethodSM2012.01 with an "in foods" claim. For Final Action in 2016, the matrix claim was reduced to rice- and corn-based matrixes. OBJECTIVE: Therefore, R-Biopharm decided to start a collaborative study to demonstrate the wide applicability of Official Method 2012.01 for the quantitative analysis of gliadin in soy, starches, pseudo cereals, legumes, spices, juice, nut nougat crème, cream cheese, pesto, meat, vegetarian meat alternative, cookies, dessert, cake, fish, bread, candies, and potatoes. Materials for incurring were the MoniQA wheat flour and the PWG gliadin preparation. RESULTS: Gliadin levels ranged from 3.4 up to 27.4 mg gliadin per kg. The results of the collaborative study with 14 participating laboratories showed recoveries ranging from 80 to 130%. Relative reproducibility standard deviations for contaminated samples were between 9.8 and 27.7%. CONCLUSIONS: The collaborative study results confirmed that the method is accurate and suitable to measure gliadin in important gluten-free food matrixes. HIGHLIGHTS: The title and applicability statement of Official Method 2012.01 were changed as proposed.


Subject(s)
Enzyme-Linked Immunosorbent Assay , Food Analysis/methods , Gliadin , Glutens , Enzyme-Linked Immunosorbent Assay/methods , Flour/analysis , Gliadin/analysis , Glutens/analysis , Reproducibility of Results , Triticum
19.
Environ Sci Technol ; 55(17): 11814-11823, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34488348

ABSTRACT

Plastic products contain complex mixtures of extractable chemicals that can be toxic. However, humans and wildlife will only be exposed to plastic chemicals that are released under realistic conditions. Thus, we investigated the toxicological and chemical profiles leaching into water from 24 everyday plastic products covering eight polymer types. We performed migration experiments over 10 days at 40 °C and analyzed the migrates using four in vitro bioassays and nontarget high-resolution mass spectrometry (UPLC-QTOF-MSE). All migrates induced baseline toxicity, 22 an oxidative stress response, 13 antiandrogenicity, and one estrogenicity. Overall, between 17 and 8681 relevant chemical features were present in the migrates. In other words, between 1 and 88% of the plastic chemicals associated with one product were migrating. Further, we tentatively identified ∼8% of all detected features implying that most plastic chemicals remain unknown. While low-density polyethylene, polyvinyl chloride, and polyurethane induced most toxicological endpoints, a generalization for other materials is not possible. Our results demonstrate that plastic products readily leach many more chemicals than previously known, some of which are toxic in vitro. This highlights that humans are exposed to many more plastic chemicals than currently considered in public health science and policies.


Subject(s)
Plastics , Polymers , Humans , Plastics/toxicity , Polyethylene
20.
United European Gastroenterol J ; 9(9): 1039-1047, 2021 11.
Article in English | MEDLINE | ID: mdl-34329537

ABSTRACT

BACKGROUND: Pyogenic liver abscesses (PLAs) represent potentially life-threatening abdominal conditions that require immediate diagnosis and therapy. European and American incidence figures vary between one and 15 per 100,000 per year. Structured epidemiological data for European countries are not available. OBJECTIVE: To systematically characterize the epidemiology and clinical outcome of PLA in Germany. METHODS: In representative statutory health insurance data from four million people in 2013-2019, the prevalence and incidence with clinical coding of International Statistical Classification of Diseases and Related Health Problems (ICD)-10 code K75.0 were selected (n = 1118). Furthermore, demographics, relevant comorbidities, hospitalizations, mortality and complications were determined within one year. RESULTS: The incidence of PLA was approximately seven per 100,000. The average age at diagnosis was 66 years; 65% were male. Of these, biliary disease was documented in over 60% and infectious intestinal diseases were found in 21% within the same or previous calendar year. PLA patients had high comorbidity indices. Liver transplant status, malignancies of the liver and biliary system, liver cirrhosis and pancreatitis were strongly associated. Intensive care was documented in 27% of PLA cases. Nine percent died within 12 months, most with an underlying malignant disease. CONCLUSION: Pyogenic liver abscess is a rare disease with high morbidity. Predisposing and risk factors include intestinal and biliary diseases as well as hepatic malignancies. Further research should focus on PLA therapy within prospective surveys and controlled clinical trials.


Subject(s)
Liver Abscess, Pyogenic/epidemiology , Liver Abscess, Pyogenic/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Biliary Tract Diseases/epidemiology , Comorbidity , Electronic Health Records , Female , Germany/epidemiology , Humans , Incidence , Insurance, Health , Intestinal Diseases/epidemiology , Liver Cirrhosis/epidemiology , Liver Transplantation , Male , Middle Aged , Neoplasms/epidemiology , Pancreatitis/epidemiology , Risk Factors , Young Adult
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