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1,2-Dehydro-pyrrolizidine alkaloids (PA), their corresponding N -oxides (PANO) and tropane alkaloids (TA), are toxic plant metabolites. If plant material, containing these toxins, is present in the feed of dairy cows these toxins can be transferred into milk. Here, milk was sampled directly from dairy farms in the German federal states of Bavaria and Schleswig-Holstein in 2020-2022 in order to investigate a possible contamination of milk at the production stage. In total, 228 milk samples were analysed for 54 PA/PANO and two TA by a sensitive LC-ESI-MS/MS method. In addition, a subset of milk samples ( n  = 85) was independently analysed for TA by a cooperating laboratory for verification. PA/PANO were found in 26 samples (11%) with a low median sum content of the contaminated samples of 0.024 µg/L. The highest level of contamination was 5.6 µg/L. Senecionine-, lycopsamine- and heliotrine-type PA/PANO were detected. In four samples (1.8%), atropine was determined up to 0.066 µg/L. The toxin levels in the milk samples hardly contributed to the total daily exposure. These data are first-time results on contamination rates and levels occurring in milk from individual dairy farms, based on a large sample number.

Background: In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood., Objective: To assess the association of IL-1β polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty., Methods: In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis., Results: We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy., Conclusion: The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Summer, Lill, Remmel, Schraml, Schopf, Banke, Kuechenhoff, Maierhofer, Endres and Thomas.)

Aims: The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD)., Methods: A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability., Results: The CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92)., Conclusion: The cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening. Cite this article: Bone Joint Res  2021;10(12):820-829.

Cortical thickness determined at the humerus can serve as an easy and reliable screening tool to predict the local bone status when quantitative bone mineral density (BMD) measurements are not available. It can therefore serve as a rapid screening tool in fragility fractures to identify patients requiring further diagnostic or osteoporosis treatment., Introduction: Quantitative bone mineral density (BMD) of the humerus is difficult to determine but relevant for osteoporosis and fracture treatment. Dual-energy X-ray absorptiometry (DXA) of the femur and lumbar spine overestimates the humeral BMD and is not ubiquitously available. Therefore, this study evaluated whether the cortical bone thickness (CBT) of the humerus or DXA of the forearm is able to predict humeral BMD., Methods: Humeral BMD of 54 upper cadaver extremities (22 pairs, 10 single) (19-90 years) was determined by high-resolution peripheral-quantitative-computed-tomography (HR-pQCT) (volumetric BMD (vBMD)) and DXA (areal BMD (aBMD)) of the proximal humerus and distal forearm. Average and gauge cortical bone thickness (CBTavg/ CBTg) of the humeral diaphysis was determined from standard radiographs (XR) and computed-tomography (CT) and compared to the humeral BMD. Pearson (r) and intraclass-correlation-coefficients (ICC) were used to compare results and rater-reliability., Results: CBTavg from XR strongly correlated with the humeral BMD (r = 0.78 aBMD (DXA) and r = 0.64 vBMD (HR-pQCT) (p < 0.0001)). The CBTg revealed a weaker correlation (r = 0.57 aBMD and r = 0.43 vBMD). CBT derived from XR strongly correlated to those from the CT (r = 0.82-0.90) and showed an excellent intra- and inter-rater correlation (ICC 0.79-0.92). Distal forearm aBMD correlated well with the humeral aBMD (DXA) (r = 0.77) and paired specimens highly correlated to the contralateral side (humerus r = 0.89, radius r = 0.97)., Conclusions: The CBTavg can reliably be determined from standard radiographs and allows a good prediction of quantitative humeral bone mineral density (aBMD or vBMD) if measurements are not available. Furthermore, the distal forearm or the contralateral humerus can serve as a side to estimate the BMD if the ipsilateral side is impaired.

A novel myosin heavy chain 7 mutation (E848G) identified in a familial cardiomyopathy was studied in patient-specific induced pluripotent stem cell-derived cardiomyocytes. The cardiomyopathic human induced pluripotent stem cell-derived cardiomyocytes exhibited reduced contractile function as single cells and engineered heart tissues, and genome-edited isogenic cells confirmed the pathogenic nature of the E848G mutation. Reduced contractility may result from impaired interaction between myosin heavy chain 7 and cardiac myosin binding protein C.

Au nanorods were used as plasmonic transducers for investigation of mercury detection through a mechanism of amalgam formation at the nanorod surfaces. Marked scattering color transitions and associated blue shifts of the surface plasmon resonance peak wavelengths ( λ max ) were measured in individual nanorods by darkfield microscopy upon chemical reduction of Hg(II). Such changes were related to compositional changes occurring as a result of Hg-Au amalgam formation as well as morphological changes in the nanorods' aspect ratios. The plot of λ max shifts vs . Hg(II) concentration showed a linear response in the 10-100 nM concentration range. The sensitivity of the system was ascribed to the narrow width of single nanorod scattering spectra, which allowed accurate determination of peak shifts. The system displayed good selectivity as the optical response obtained for mercury was one order of magnitude higher than the response obtained with competitor ions. Analysis of mercury content in river and tap water were also performed and highlighted both the potential and limitation of the developed method for real sensing applications.

When exposed to enhanced background noise, humans avoid signal masking by increasing the amplitude of the voice, a phenomenon termed the Lombard effect. This auditory feedback-mediated voice control has also been found in monkeys, bats, cetaceans, fish and some frogs and birds. We studied the Lombard effect for the first time in a phylogenetically basal primate, the grey mouse lemur, Microcebus murinus. When background noise was increased, mouse lemurs were able to raise the amplitude of the voice, comparable to monkeys, but they did not show this effect consistently across context/individuals. The Lombard effect, even if representing a generic vocal communication system property of mammals, may thus be affected by more complex mechanisms. The present findings emphasize an effect of context, and individual, and the need for further standardized approaches to disentangle the multiple system properties of mammalian vocal communication, important for understanding the evolution of the unique human faculty of speech and language.

We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer's disease-like pathologies in the aging brain.

Droplet evaporation is a simple method to induce organization of Au nanorods into ordered superstructures. In general, the self-assembly process occurs by evaporation of aqueous suspensions under strictly controlled experimental conditions. Here we present formation of large area ordered vertical arrays by droplet evaporation of Au nanorod organic suspensions. The uncontrolled (free air) evaporation of such suspensions yielded to formation of ordered nanorod domains covering the entire area of a 5 mm diameter droplet. Detailed investigation of the process revealed that nanorods organized into highly ordered vertical domains at the interface between solvent and air on a fast time scale (minutes). The self-assembly process mainly depended on the initial concentration of nanorod solution and required minimal control of other experimental parameters. Nanorod arrays displayed distinct optical properties which were analyzed by optical imaging and spectroscopy and compared to results obtained from theoretical calculations. The potential use of synthesized arrays as surface-enhanced Raman scattering probes was demonstrated with the model molecule 4-aminobenzenthiol.

Background: Data on implant allergies are incomplete; therefore, we compared the data on allergy history, patch test (PT) and lymphocyte transformation test (LTT) results in a patient series from the Munich implant allergy outpatient department with symptom-free arthroplasty patients., Patients and Methods: In this study 200 arthroplasty patients with complaints involving the prosthesis (130 female, 187 knee and 13 hip prostheses) and in parallel 100 symptom-free patients (75 female, 47 knee and 53 hip prostheses) were investigated. A questionnaire-aided history including implant type, cementing, intolerance of dental materials, atopy, cutaneous metal intolerance (CMI) and PT, including a standard series with Ni, Co, Cr, seven bone cement components, including gentamicin and benzoyl peroxide and LTT for Ni, Co and Cr., Results: In the knee arthroplasty patients with complaints 9.1% showed dental material intolerance, 23.5% atopy, 25.7% CMI, 18.2% metal allergies, 7.4% gentamicin allergy and 27.8% positive metal LTT (mostly to Ni). In symptom-free patients 0% showed dental material intolerance, 19.1% atopy, 12.8% CMI, 12.8% metal allergy, 0% gentamicin allergy and 17% positive metal LTT., Conclusions: Characteristics of the patients with complaints were increased intolerance of dental materials, higher rates of atopy, CMI, metal and gentamicin allergy and LTT reactivity.

In the course of demographic change, the number of elderly migrants increases, and the population of elderly people in Germany becomes more varied-facts that have to be taken into account more intensely when it comes to planning services for elderly people in the future. The need for action is intensified by the fact that elderly migrants are still worse off than natives of the same age in many areas of life (e. g. income, health, etc.). At the same time, elderly migrants cannot automatically be regarded as helpless or isolated because of their solid family help networks.Meanwhile, on political and social levels, approaches have been developed to open services and institutions for the special needs of minority ethnic elders. Furthermore, offers have been established by the creation of ethnic-specific emphases that focus on the life style and the everyday life of the target group. In spite of all these efforts, the whole range of care services for the population of elderly migrants is still regarded as insufficient by experts. Therefore, especially in the fields of networking, cooperation and controlling of the people involved, information transfer, and training measures that aim at better preparing the provider of care services for elderly people are highly recommended in order to meet the increasing needs of help and care of older migrants more precisely.

Aim: In spite of available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. In a retrospective study, the possibilities and results of complete, full-thickness chest wall resection are presented., Methods: Between 1985 and 2004, 51 women underwent complete, full-thickness chest wall resection with primary coverage. Primary surgical therapy of breast cancer had been mastectomy in 88%. Median age of patients undergoing surgery for a local recurrence was 57 (29 - 81) years. The median interval between surgery of the primary tumour and of the local recurrence was 70.3 (10.7 - 327.2) months; median follow-up was 29.4 (1.8 - 230.9) months. 40 (78.4%) patients required rib resections, 15 (29.4%) of them in combination with partial sternal resection. In 4 (7.8%) patients complete and in 7 (13.7%) patients partial sternal resection without additional rib resection were performed.Coverage was mainly realized using latissimus dorsi myocutaneous flaps (n=44; 86.3%). Survival rates were calculated by means of the Kaplan-Meier method, the relative risk using univariate and multivariate Cox-regression analysis., Results: In the total collective, cumulative 5-, 10- and 15-year survival (YS) rates were 39%, 31% and 23%, respectively, median survival 46.4 months. R0 resection was associated with a 5-YS of 42%. Prognostic factors were age at the time of primary surgery, disease-free interval and tumour invasion of bony structures. Mortality was 2%, morbidity 35%., Conclusion: Full-thickness chest wall resection of locally recurrent breast cancer is possible in almost any patient when performed by a team of thoracic and plastic surgeons. Only radical resection provides good long-term results with low mortality and morbidity.

Circulating antibodies directed against cytoplasmic antigens of basal cells of normal human epidermis have been reported in association with various skin diseases. Since they have been found in patients with malignant melanoma it was proposed to investigate whether these antibodies are associated with other epidermal tumors such as basal or squamous cell carcinoma. With indirect immunofluorescence it was shown that sera from patients with basal (20%) and squamous cell carcinoma (16%) contained these antibodies. They could be demonstrated by cytoplasmic fluorescence of the basal epidermal cell layer. These antibodies occured almost as frequent as in malignant melanoma sera. However they do not seem to be tumorassociated as they were found in sera from patients with various benign dermatoses, with tumors of extraepidermal origin and even sporadically in sera from natural antibodies which were identified by cytoplasmic fluorescence of the outer epidermal cells, suggesting two antigenically different epidermal cell populations.

Clinical observations on two cases of staphylodermia superficialis circinata are reported. This rare variation of superificial staphylococcal skin infection is identical with the "erythema necroticans migrans". As this cutaneous manifestation is highly associated with malignant internal diseases it must be regarded as a "cutaneous paraneoplasia". Out of 14 cases of erythema necroticans migrans, so far published this dermatosis occured in 13 patients suffering from pancreatic cancer. Association with pancreatitis was demonstrated in one case. In both cases herein reported the cutaneous manifestations were associated with a carcinoma of the pancreas and with cervix cancer. Extreme loss of weight, atrophic glossitis, therapy-resistant anemia and a slight diabetes are extra-cutaneous symptoms of this paraneoplastic syndrom.