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Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown.Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort.Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed.While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

East Africa is a hotspot for foodborne diseases, including infection by nontyphoidal Salmonella (NTS), a zoonotic pathogen that may originate from livestock. Urbanization and increased demand for animal protein drive intensification of livestock production and food processing, creating risks and opportunities for food safety. We built a probabilistic mathematical model, informed by prior beliefs and dedicated stakeholder interviews and microbiological research, to describe sources and prevalence of NTS along the beef supply chain in Moshi, Tanzania. The supply chain was conceptualized using a bow tie model, with terminal livestock markets as pinch point, and a forked pathway postmarket to compare traditional and emerging supply chains. NTS was detected in 36 (7.7%) of 467 samples throughout the supply chain. After combining prior belief and observational data, marginal estimates of true NTS prevalence were 4% in feces of cattle entering the beef supply and 20% in raw meat at butcheries. Based on our model and sensitivity analyses, true NTS prevalence was not significantly different between supply chains. Environmental contamination, associated with butchers and vendors, was estimated to be the most likely source of NTS in meat for human consumption. The model provides a framework for assessing the origin and propagation of NTS along meat supply chains. It can be used to inform decision making when economic factors cause changes in beef production and consumption, such as where to target interventions to reduce risks to consumers. Through sensitivity and value of information analyses, the model also helps to prioritize investment in additional research.

The intracellular adaptor protein Mint2 binds amyloid precursor protein (APP) and presenilin-1, which are both central constituents of the amyloidogenic pathway associated with Alzheimer's disease (AD). Additional interaction partners have also been suggested for Mint2; several of them are also pertinent to AD pathogenesis. However, no comparative mapping of the Mint2 protein-protein interaction network is available. Here we provide a systematic characterization of seven interaction partners and address their specificities towards the different binding domains of Mint2, which reveal domain-specific and -nonspecific interaction partners. Moreover, we show that the last two C-terminal amino acids of Mint2 are both important for the intramolecular interaction with the PDZ1 domain and for the stability of Mint2.

Ionic liquids with perfluorinated side chains are prepared as hybrid materials for surface impregnation. For the cationic part, methyl and ethyl pyridinium as well as imidazolium scaffolds are used. The anions are hydroxide, acetate, trifluoroacetate, triflate, triflimide, chloride, bromide, iodide, hydrogensulfate, and perfluorododecanoate. The key feature of this investigation are relatively short perfluorohexyl residues as the fluorinated part of the salts, making the target compounds beneficial alternatives to established products because of their lower bioaccumulativity. One compound yielded single crystals suitable for X-ray structure analysis revealing a layered structure with relatively well-resolved, hard ionic domains alternating with disordered, soft perfluorinated layers. The wettability of all 30 materials was investigated by water contact angle measurements of a thin film on a glass surface. In two cases, promising contact angles (130° and 140°) were observed indicating, that the products might be suitable candidates for the impregnation of surfaces.

Calcium ions regulate mitochondrial ATP production and contractile activity and thus play a pivotal role in matching energy supply and demand in cardiac muscle. Little is known about the magnitude and kinetics of the changes in free mitochondrial calcium concentration in cardiomyocytes. Using adenoviral infection, a ratiometric mitochondrially-targeted FRET-based calcium indicator (4 mtD3cpv, MitoCam) was expressed in cultured adult rat cardiomyocytes and the free mitochondrial calcium concentration ([Ca2+]m) was measured at different stimulation frequencies (0.1-4 Hz) and external calcium concentrations (1.8-3.6 mM) at 37°C. Cytosolic calcium concentrations were assessed under the same experimental conditions in separate experiments using Fura-4AM. The increases in [Ca2+]m during electrical stimulation at 0.1 Hz were rapid (rise time = 49 ± 2 ms), while the decreases in [Ca2+]m occurred more slowly (decay half time = 1.17 ± 0.07 s). Model calculations confirmed that this asymmetry caused the rise in [Ca2+]m during diastole observed at elevated stimulation frequencies. Inhibition of the mitochondrial sodium-calcium exchanger (mNCE) resulted in a rise in [Ca2+]m at baseline and -paradoxically- in an acceleration of Ca2+-release. In conclusion: rapid increases in [Ca2+]m allow for fast adjustment of mitochondrial ATP production to increases in myocardial demand on a beat-to-beat basis and mitochondrial calcium release depends on mNCE activity and mitochondrial calcium buffering. This article is protected by copyright. All rights reserved

Objective To compare the effects of pressure controlled ventilation (PCV) with volume-controlled ventilation (VCV) on lung compliance, gas exchange, and hemodynamics in isoflurane-anesthetized dogs. Design Prospective randomized study. Setting Veterinary teaching hospital. Animals Forty client-owned bitches undergoing elective ovariohysterectomy. Interventions Dogs were randomly assigned to be ventilated with 100% oxygen using PCV (n = 20) or VCV (n = 20). The respiratory rate was 20/min and positive end-expiratory pressure (PEEP) was 5 cm H2O, with a tidal volume of 10 mL/kg. Cardiac output (CO) was measured using thermodilution. Cardiopulmonary and blood gas data were obtained during spontaneous ventilation and after 30 (T30) and 60 minutes (T60) of controlled ventilation. Measurements and Main Results In dogs ventilated with PCV, at T30 and T60, PIP was lower (11.4 ± 1.9 and 11.1 ± 1.5 cm H2O, respectively) and static compliance (CST) was higher (51 ± 7 and 56 ± 6 mL/cm H2O, respectively) than in VCV group (PIP of 14.3 ± 1.3 and 15.5 ± 1.4 cm H2O; CST of 34 ± 8 and 33 ± 9 mL/cm H2O, P < 0.0001). Compared with spontaneous ventilation, both groups had decreased alveolar-arterial oxygen difference at T30 and T60 (PCV: 128 ± 32 mm Hg vs 108 ± 20 and 104 ± 16 mm Hg, respectively; VCV: 131 ± 38 mm Hg vs 109 ± 19 and 107 ± 14 mm Hg, respectively; P < 0.01), while CO was maintained at all time points. Conclusions Compared to spontaneous ventilation, both ventilatory modes effectively improved gas exchange without hemodynamic impairment. PCV resulted in higher lung CST and lower PIP compared to VCV.

Reaction of 4,4'-tolanedisulfonic acid, H2 TDS, with zinc hydroxide in dimethylacetamide, DMA, under solvothermal conditions led to the coordination polymer Zn(TDS)(DMA)3 (I). In the crystal structure [trigonal, P32 21, Z=3, a=1175.0(1) pm, c=1949.5(1) pm, R1 ; wR2 (Io > 2σ(Io ))=0.0393; 0.0921] the disulfonate anions linked the Zn(2+) ions into helical chains according to ∞ (1) [Zn(DMA)3/1 (TDS)2/2 ] (I) causing the chirality of the compound. By using higher concentrations of H2 TDS in the starting mixture the compound [HDMA]2 [Zn(TDS)2 (DMA)3 ](DMA)2 (II) was formed. The structure [monoclinic, Cc, Z=4, a=1201.5(1) pm, b=1996.0(1) pm, c=2749.2(2) pm, β=101.897(2)°, R1 ; wR2 (Io > 2σ(Io ))=0.0699; 0.2017] displayed the complex anion [Zn(TDS)2 (DMA)3 ](2-) which was a perfect cut-off of the helical chain in I. Charge compensation was achieved by protonated DMA molecules. If N-methylpyrrolidone, NMP, was chosen as a solvent, the sulfonate Zn(TDS)(NMP)3 (III) [monoclinic, I2/a, Z=4, a=1575.7(1) pm, b=1077.3(1) pm, c=1870.0(1) pm, β=101.189(9)°, R1 ; wR2 (Io > 2σ(Io ))=0.0563; 0.1320] was obtained. Similarly to the findings for I, the formation of chains according to ∞ (1) [Zn(NMP)3/1 (TDS)2/2 ] was observed. However, due to the more bulky NMP molecules these chains were no longer helical but straight instead.

Polysulfonic acids and their compounds have been scarcely investigated, despite the huge knowledge that we have of the respective polycarboxylic acids and polycarboxylates. This is because of the limited availability of polysulfonic acids, for which reliable synthetic protocols are often lacking. Here, we present the first compound of the recently reported disulfonic acid 1,4-bis(4-sulfophenyl)butadiyne (H2DPBDS) prepared in our groups and a new compound of the commercially available 4,4′-biphenyldisulfonic acid (H2BPDS). The zinc sulfonates [Zn2(BPDS)2(NMP)6]·2NMP [I, NMP = N-methylpyrrolidone; triclinic, P, Z = 2, a = 972.8(2), b = 981.5(2), c = 1915.2(2) pm, α = 87.73(3)°, β = 77.68(3)°, γ = 89.36(3)°, V = 1785.0(6) A3] and [Zn2(DPBDS)2(DMA)6]·2DMA [II, DMA = dimethylacetamide; triclinic, P, Z = 2, a = 973.79(2), b = 1347.53(2), c = 1411.08(2) pm, α = 110.531(1)°, β = 92.445(1)°, γ = 101.931(1)° V = 1683.11(5) A3] display rigid molecular rectangles constructed from two zinc atoms and two sulfonate ligands. The rectangles are assembled through weak interactions to form soft host lattices that incorporate the solvent DMA or NMP molecules, partly through Zn2+ coordination. Thermal analysis shows that the solvent molecules can be completely removed without decomposition of the coordination polymers.