A Quasi Real-Time Evaluation of High-Resolution Mass Spectra of Complex Chlorinated Paraffin Mixtures and Their Transformation Products.

Chlorinated paraffins (CPs) are complex mixtures of polychlorinated n-alkanes with multiple carbon- (C-, nC = 9-30) and chlorine homologues (Cl-, nCl = 3-18). The mass spectrometric analysis of CPs is time-consuming and challenging, especially when interferences between CPs, their transformation products, or from the matrix are numerous. These analytical challenges and the lack of appropriate and accessible data evaluation tools are obstacles to their analysis. CP-Hunter is a web-based, open-access data processing platform for the automatic analysis of mass spectra of CPs and their transformation products. Extracts of two consumer plastic materials and sewage sludge were evaluated with CP-Hunter. C- and Cl-homologue distributions were obtained in quasi-real-time and the posterior calculated fingerprints were in agreement with the ones obtained by traditional methods. However, the data extraction and evaluation time were now reduced from several minutes to seconds. The implemented signal deconvolution method, i.e., to resolve mass spectrometric interferences, provides robust results, even when severe matrix effects are present. CP-Hunter facilitates the untargeted analysis of unknown products and the detection and elimination of false positive signals. Finally, data evaluation with CP-Hunter is performed locally without the transfer of data to external servers. The tool is safe, public, and accessible at https://cphunter.cheminfo.org/.

A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation.

Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. During gemination, spores must degrade their cortex layer, which is a thick, protective layer of modified peptidoglycan. Cortex degradation depends on the presence of the spore-specific peptidoglycan modification, muramic-∂-lactam (MAL), which is specifically recognized by cortex lytic enzymes. In C. difficile, MAL production depends on the CwlD amidase and its binding partner, the GerS lipoprotein. To gain insight into how GerS regulates CwlD activity, we solved the crystal structure of the CwlD:GerS complex. In this structure, a GerS homodimer is bound to two CwlD monomers such that the CwlD active sites are exposed. Although CwlD structurally resembles amidase_3 family members, we found that CwlD does not bind Zn2+ stably on its own, unlike previously characterized amidase_3 enzymes. Instead, GerS binding to CwlD promotes CwlD binding to Zn2+, which is required for its catalytic mechanism. Thus, in determining the first structure of an amidase bound to its regulator, we reveal stabilization of Zn2+ co-factor binding as a novel mechanism for regulating bacterial amidase activity. Our results further suggest that allosteric regulation by binding partners may be a more widespread mode for regulating bacterial amidase activity than previously thought.

Monitoring the neural activity associated with praying in Sahaja Yoga meditation.

BACKGROUND: Sahaja Yoga Meditation draws on many religious traditions and uses a variety of techniques including Christian prayer to reach a state known as thoughtless awareness, or mental silence. While there are many studies on the neural correlates of meditation, few studies have focused on the neural correlates of praying. Thus, the aim of our research was to study the neural activity associated with the prayer practices in Sahaja Yoga Mediation, which have not been studied before, to explore effects beyond repetitive speech or "mantra effects". Sixteen experienced Sahaja Yoga Meditation practitioners were scanned using task based functional Magnetic Resonance Imaging while performing formalised and improvised forms of praying and their equivalent secular tasks. RESULTS: Our results showed the deactivation of bilateral thalamus during both prayers compared to secular conditions and the activation in the medial prefrontal cortex that was reduced by religious and formalised secular speech conditions but increased during improvised secular speech; similarly, frontal regions were deactivated when comparing prayers to their secular equivalents. DISCUSSION: These results seem to depict two important factors related with praying in Sahaja Yoga Meditation merging inner concentration and social cognition. First, the perception of the surroundings mediated by the thalamus may be decreased during these prayers probably due to the establishment of inner concentration and, second, frontal deactivation effects could be related to reduced social judgement and 'mentalizing', particularly in the medial prefrontal cortex. Our findings suggest that praying by Sahaja Yoga Meditation practitioners is neurophenomenologically different from the social cognitive attempt of praying within Christian praying practices.

Selective and Fast Analysis of Chlorinated Paraffins in the Presence of Chlorinated Mono-, Di-, and Tri-Olefins with the R-Based Automated Spectra Evaluation Routine (RASER).

Chlorinated paraffins (CPs) are complex mixtures consisting of various C homologues (nC ≈ 10-30) and Cl homologues (nCl ≈ 2-20). Technical CP mixtures are produced on a large scale (>106 t/y) and are widely used such as plasticizers in plastic and coolants in metalwork. Since 2017, short-chain CPs (C10-C13) are classified as persistent organic pollutants (POPs) by the Stockholm Convention but longer-chain CPs are not regulated. Analysis of technical CP mixtures is challenging because they consist of hundreds of homologues and millions of constitutional isomers and stereoisomers. Furthermore, such mixtures can also contain byproducts and transformation products such as chlorinated olefins (COs). We applied a liquid-chromatography method coupled to an atmospheric pressure chemical ionization technique with a high-resolution mass detector (LC-APCI-Orbitrap-MS) to study CP and CO homologues in two plastic materials. Respective mass spectra can contain up to 23,000 signals from 1320 different C-Cl homologue classes. The R-based automated spectra evaluation routine (RASER) was developed to efficiently search for characteristic ions in these complex mass spectra. With it, the time needed to evaluate such spectra was reduced from weeks to hours, compared to manual data evaluation. Unique sets of homologue distributions could be obtained from the two plastic materials. CPs were found together with their transformation products, the chlorinated mono-olefins (COs), di-olefins (CdiOs), and tri-olefins (CtriOs) in both plastic materials. Based on these examples, it can be shown that RASER is an efficient and selective tool for evaluating high-resolution mass spectra of CP mixtures containing hundreds of homologues.

Forecasting COVID-19 Chile' second outbreak by a generalized SIR model with constant time delays and a fitted positivity rate.

The COVID-19 disease has forced countries to make a considerable collaborative effort between scientists and governments to provide indicators to suitable follow-up the pandemic's consequences. Mathematical modeling plays a crucial role in quantifying indicators describing diverse aspects of the pandemic. Consequently, this work aims to develop a clear, efficient, and reproducible methodology for parameter optimization, whose implementation is illustrated using data from three representative regions from Chile and a suitable generalized SIR model together with a fitted positivity rate. Our results reproduce the general trend of the infected's curve, distinguishing the reported and real cases. Finally, our methodology is robust, and it allows us to forecast a second outbreak of COVID-19 and the infection fatality rate of COVID-19 qualitatively according to the reported dead cases.

Developing research questions in conversation with the literature: operationalization & tool support.

Empirical Software Engineering rests on the understanding of practical problems and their solution counterparts. Frequently, solutions are not absolute but relative to the context where the problem is observed. This tends to imply that the solution and the problem unveil gradually together, and hence, researchers are not always in the position to state the research question (RQ) at the onset. Like software engineers when facing blurred requirements, researchers might not be familiar enough with the problem in the early phases of a research to properly scope their RQs (hereafter referred to as RQ Scoping). Here, the literature may play the role of the stakeholders in Agile methods: keeping the focus on the aspects that are essential (vs. accidental) of the RQ. Informed by Inductive Top-Down Theorizing, this article acknowledges RQ Scoping as iterative and incremental, entailing a conversation between the experimental work and literature reviewing. Yet, for literature reviewing to become "Agile" it is not only required to be driven by the RQ but also to have tool support. Tools might bring transparency and traceability, both factors especially welcome in a scenario characterized by testing (is my RQ relevant?) and adjustment (how can I make my RQ relevant?). Specifically, the advent of the RQ in close relationship with the literature advises for "Agile" literature reviewing to be conducted at the place where the literature is naturally kept: the Reference Management System (e.g., Mendeley). This article introduces the theoretical underpinnings, design principles, proof of concept and evaluation for FRAMEndeley, a Mendeley-integrated utility for RQ Scoping.

Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants.

BACKGROUND: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear. METHODS: In 1996-2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006-08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35-79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, 'usual') levels of SBP and BMI. RESULTS: After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively. CONCLUSIONS: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.

Avoiding a Second Wave of Medical Errors: The Importance of Human Factors in the Context of a Pandemic.

The COVID-19 pandemic has had an unprecedented impact on the delivery of healthcare services around the globe. This has resulted in important loss of life for our communities, including health professionals that have been exposed to the disease in their workplace. A human factors approach to the recent changes introduced due to the pandemic can help identify how we can minimize the impact of human error in these circumstances. We hereby present a case study illustrating the application of human factors in the difficult times we are going through at present.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spatial Dynamics of Chikungunya Virus, Venezuela, 2014.

Since chikungunya virus emerged in the Caribbean region in late 2013, ≈45 countries have experienced chikungunya outbreaks. We described and quantified the spatial and temporal events after the introduction and propagation of chikungunya into an immunologically naive population from the urban north-central region of Venezuela during 2014. The epidemic curve (n = 810 cases) unraveled within 5 months with a basic reproductive number of 3.7 and a radial spread traveled distance of 9.4 km at a mean velocity of 82.9 m/day. The highest disease diffusion speed occurred during the first 90 days, and space and space-time modeling suggest the epidemic followed a particular geographic pathway with spatiotemporal aggregation. The directionality and heterogeneity of transmission during the first introduction of chikungunya indicated existence of areas of diffusion and elevated risk for disease and highlight the importance of epidemic preparedness. This information will help in managing future threats of new or reemerging arboviruses.

Using Health Chatbots for Behavior Change: A Mapping Study.

This study conducts a mapping study to survey the landscape of health chatbots along three research questions: What illnesses are chatbots tackling? What patient competences are chatbots aimed at? Which chatbot technical enablers are of most interest in the health domain? We identify 30 articles related to health chatbots from 2014 to 2018. We analyze the selected articles qualitatively and extract a triplet for each of them. This data serves to provide a first overview of chatbot-mediated behavior change on the health domain. Main insights include: nutritional disorders and neurological disorders as the main illness areas being tackled; "affect" as the human competence most pursued by chatbots to attain change behavior; and "personalization" and "consumability" as the most appreciated technical enablers. On the other hand, main limitations include lack of adherence to good practices to case-study reporting, and a deeper look at the broader sociological implications brought by this technology.

Growth Hormone (GH) and Cardiovascular System.

This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases.

Plant characterization of genetically modified maize hybrids MON-89Ø34-3 × MON-88Ø17-3, MON-89Ø34-3 × MON-ØØ6Ø3-6, and MON-ØØ6Ø3-6: alternatives for maize production in Mexico.

Environmental risk assessment (ERA) of genetically modified (GM) crops is a process to evaluate whether the biotechnology trait(s) in a GM crop may result in increased pest potential or harm to the environment. In this analysis, two GM insect-resistant (IR) herbicide-tolerant maize hybrids (MON-89Ø34-3 × MON-88Ø17-3 and MON-89Ø34-3 × MON-ØØ6Ø3-6) and one herbicide-tolerant GM hybrid (MON-ØØ6Ø3-6) were compared with conventional maize hybrids of similar genetic backgrounds. Two sets of studies, Experimental Phase and Pilot Phase, were conducted across five ecological regions (ecoregions) in Mexico during 2009-2013, and data were subject to meta-analysis. Results from the Experimental Phase studies, which were used for ERA, indicated that the three GM hybrids were not different from conventional maize for early stand count, days-to-silking, days-to-anthesis, root lodging, stalk lodging, or final stand count. Statistically significant differences were observed for seedling vigor, ear height, plant height, grain moisture, and grain yield, particularly in the IR hybrids; however, none of these phenotypic differences are expected to contribute to a biological or ecological change that would result in an increased pest potential or ecological risk when cultivating these GM hybrids. Overall, results from the Experimental Phase studies are consistent with those from other world regions, confirming that there are no additional risks compared to conventional maize. Results from Pilot Phase studies indicated that, compared to conventional maize hybrids, no differences were detected for the agronomic and phenotypic characteristics measured on the three GM maize hybrids, with the exception of grain moisture and grain yield in the IR hybrids. Since MON-89Ø34-3 × MON-88Ø17-3 and MON-89Ø34-3 × MON-ØØ6Ø3-6 confer resistance to target insect pests, they are an alternative for farmers in Mexico to protect the crop from insect damage. Additionally, the herbicide tolerance conferred by all three GM hybrids enables more cost-effective weed management.

Mazzaella laminarioides and Sarcothalia crispata as possible bioindicators of heavy metal contamination in the marine coastal zone of Chile.

The suitability of Mazzaella laminarioides and Sarcothalia crispata as heavy metal biomonitors of Cd, Cu, Hg, Pb, and Zn was assessed by comparing bioaccumulation of these elements in different life stages and frond sizes in samples from three locations, San Vicente Bay (industrial area), Coliumo, and Quidico (the latter as a reference station), where different degrees of heavy metal pollution are recorded. Bioaccumulation and bioconcentration factors of Cd, Cu, Hg, Pb, and Zn were evaluated. The two macroalgae species showed similar patterns, with higher values of Cu, Hg, Pb, and Zn in polluted areas. M. laminarioides bioaccumulated higher concentrations of all metals assessed than S. crispata, independent of life stage and frond size. The results also showed significantly higher Cu, Hg, Pb, and Zn concentrations (p < 0.05) in water samples from San Vicente Bay than those measured in Coliumo and Quidico. Concentrations of Cd, Hg, Pb, and Zn in San Vicente Bay and Cd, Hg, and Pb in Coliumo and Quidico exceed the mean values considered to represent natural concentrations (Cu = 3.00 µg L-1; Zn = 5.00 µg L-1; Pb = 0.03 µg L-1; Cd = 0.05 µg L-1; Hg = 0.05 µg L-1); however, the concentrations recorded do not cause negative effects on the growth and survival of macroalgae. The assessment of heavy metals bioaccumulated in M. laminarioides and S. crispata, particularly Hg, Pb, and Zn, offers a reliable approach for pollution assessment in rocky intertidal environments. Cu and Cd concentrations in seawater samples from San Vicente and Coliumo Bays were significantly higher than in those from Quidico (p value < 0.05); no significant differences in Cd concentrations were observed between San Vicente and Coliumo Bays (p < 0.05). Exceptionally, Cd is bioaccumulated at high levels independent of its availability in the water, thus reaching high concentrations in control areas. High concentrations of metals like Cu and Zn may limit or inhibit Cd uptake in macroalgae, since the transport channels are saturated by some metals, reducing the accumulation of others. These macroalgae species offer good potential for the development of suitable heavy metal pollution survey tools in rocky intertidal environments.

Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.

Evidence from C57BL/6 mice suggests that CD8(+) T cells, specific to the immunodominant HSV-1 glycoprotein B (gB) H-2(b)-restricted epitope (gB498-505), protect against ocular herpes infection and disease. However, the possible role of CD8(+) T cells, specific to HLA-restricted gB epitopes, in protective immunity seen in HSV-1-seropositive asymptomatic (ASYMP) healthy individuals (who have never had clinical herpes) remains to be determined. In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence. Six of these epitopes exhibited high-affinity binding to HLA-A*02:01 molecules. In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569. In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449). ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals. Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease. These findings should guide the development of a safe and effective T cell-based herpes vaccine.

Maintaining Functionality in Temporal Skin Tumor Surgery: A Focus on Nerve Injury and Excision Margins.

Background: Operating on temporal cutaneous tumors is challenging because of the intricate facial nerve system, particularly the frontal branches, and the possibility of brow dysfunction. Surgery for deep margin clearance is difficult because of the fragile and sensitive soft tissue in the temporal region. To address this research gap, this study assessed clearance margins, types of skin tumors, and nerve injuries in this critical anatomical position. This retrospective study assessed temporal skin cancer surgery, malignancy types, and clearance margins in patients with frontal-branch facial nerve injuries. Methods: Forty-five patients with temporal skin carcinoma biopsies were analyzed. The deep and peripheral excision margins of skin malignancies were examined. Medical records were reviewed for clinically injured frontal nerve. Results: Thirty-four patients were men (75%), and basal cell carcinoma was the most prevalent histological malignancy, followed by squamous cell carcinoma. The mean age of the patients was 77.8 years (39-107 years). Two patients experienced damage to the frontal branch nerve. Twenty-six percent of the skin malignancies had inadequate deep margin excision. Conclusions: Removing temporal skin lesions is difficult. We discovered a 26% and 4% probability of inadequate deep margin excision and frontal branch facial nerve injury, respectively. Temporal skin lesions must be removed safely by surgeons to preserve the branches of the facial nerves. Insufficiently removed tumors require multidisciplinary teamwork and patient discussions regarding the advantages and risks to improve results.

Enhanced amygdala-anterior cingulate white matter structural connectivity in Sahaja Yoga Meditators.

OBJECTIVE: To study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation. DESIGN: Twenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses. RESULTS: There were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

Management of Immobile Scalp Skin Tumors and Analysis of Skin Graft Survival on Burred Calvaria.

Background: Surgeons face challenges associated with adherent cutaneous scalp malignancy. Traditional general anesthetic excision involves periosteal removal and burring of the outer table of the calvaria for deep margin clarity and tissue reconstruction. Research on this practice is limited, and graft survival in burr-treated bones is underexplored. This study aimed to assess the clinical margin accuracy for immobile scalp malignancies, identify deep-invading malignancy types, and evaluate graft survival in burr-treated calvariae. It compares split-thickness grafts (STSGs) and full-thickness grafts (FTSGs). Methods: Twelve fixed scalp malignancies were excised under anesthesia, allowing immediate STSG or FTSG for defect reconstruction. Postsurgery, graft take, malignancy type, and margin clearance were evaluated. Results: Histopathological diagnosis identified seven squamous cell carcinomas, two melanomas, one basal cell carcinoma, one adenocarcinoma, and one metastatic squamous cell carcinoma. Deep margins ranged from 0 to 0.9 mm, and peripheral margins ranged from 0 to 15 mm. The graft take was 100% in eight cases, with total failure in two cases, and 75%-90% in two cases. The five STSGs had 100% take and 90% take. The three FTSGs had 100%, 75%, and two failed. Conclusions: Clinical examination effectively gauges the tumor fixation depth, but large lesions may require imaging. Most deep-invading tumors were SCCs. STSGs performed better on burr-treated Calvaria than FTSGs.

Evolution of chlorinated paraffin and olefin fingerprints in sewage sludge from 1993 to 2020 of a Swiss municipal wastewater treatment plant.

Exposure of humans to chlorinated paraffins (CPs) and chlorinated olefins (COs) can occur via contact with CP-containing plastic materials. Such plastic materials can contain short-chain CPs (SCCPs), which are regulated as persistent organic pollutants (POPs) under the Stockholm Convention since 2017. Municipal wastewater treatment plants (WWTP) collect effluents of thousands of households and their sludge is a marker for CP exposure. We investigated digested sewage sludge collected in the years 1993, 2002, 2007, 2012, and 2020 from a Swiss WWTP serving between 20000 and 23000 inhabitants. A liquid chromatography mass spectrometry (R > 100000) method, in combination with an atmospheric pressure chemical ionization source (LC-APCI-MS), was used to detect mass spectra of CPs and olefinic side products. A R-based automated spectra evaluation routine (RASER) was applied to search for ∼23000 ions whereof ∼6000 ions could be assigned to CPs, chlorinated mono- (COs), di- (CdiOs) and tri-olefins (CtriOs). Up to 230 CP-, 120 CO-, 50 CdiO- and 20 CtriO-homologues could be identified in sludge. Characteristic fingerprints were deduced describing C- and Cl-homologue distributions, chlorine- (nCl) and carbon- (nC) numbers of CPs and COs. In addition, proportions of saturated and unsaturated material were determined together with proportions of different chain length classes including short- (SC), medium- (MC), long- (LC) and very long-chain (vLC) material. A substantial reduction of SCCPs of 84% was observed from 1993 to 2020. Respective levels of MCCPs, LCCPs and vLCCPs decreased by 61, 69 and 58%. These trends confirm that banned SCCPs and non-regulated CPs are present in WWTP sludge and higher-chlorinated SCCPs were replaced by lower chlorinated MCCPs. Combining high-resolution mass spectrometry with a selective and fast data evaluation method can produce characteristic fingerprints of sewage sludge describing the long-term trends in a WWTP catchment area.

Intestinal damage is required for the pro-inflammatory differentiation of commensal CBir1-specific T cells.

Commensal-specific clusters of differentiation (CD)4+ T cells are expanded in patients with inflammatory bowel disease (IBD) compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used CBir1 TCR-transgenic CD4+ T cells, specific to a commensal bacterial antigen, and different mouse models of IBD to characterize the dynamics of commensal-specific CD4+ T-cells activation. We found that CBir1 T cells proliferate following intestinal damage and cognate antigen presentation is mediated by CD11c+ cells in the colon-draining mesenteric lymph nodes. Using assay for transposase-accessible chromatin sequencing and flow cytometry, we showed that activated CBir1 T cells preferentially acquire an effector rather than regulatory phenotype, which is plastic over time. Moreover, CBir1 T cells, while insufficient to initiate intestinal inflammation, contributed to worse disease outcomes in the presence of other CD4+ T cells. Our results suggest that the commensal-specific T-cell responses observed in IBD exacerbate rather than initiate disease.

Differentiation at autopsy between in vivo gas embolism and putrefaction using gas composition analysis.

Gas embolism can arise from different causes (iatrogenic accidents, criminal interventions, or diving related accidents). Gas analyses have been shown to be a valid technique to differentiate between putrefaction gases and gas embolism. In this study, we performed systematic necropsies at different postmortem times in three experimental New Zealand White Rabbits models: control or putrefaction, infused air embolism, and compression/decompression. The purpose of this study was to look for qualitative and quantitative differences among groups and to observe how putrefaction gases mask in vivo gas embolism. We found that the infused air embolism and compression/decompression models had a similar gas composition prior to 27-h postmortem, being typically composed of around 70-80 % of N(2) and 20-30 % of CO(2), although unexpected higher CO(2) concentrations were found in some decompressed animals, putting in question the role of CO(2) in decompression. All these samples were statistically and significantly different from more decomposed samples. Gas composition of samples from more decomposed animals and from the putrefaction model presented hydrogen, which was therefore considered as a putrefaction marker.