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This study aimed to evaluate protection induced by the vaccine candidate B. ovis ΔabcBA against experimental challenge with wild type B. ovis in rams. Rams were subcutaneously immunized with B. ovis ΔabcBA encapsulated with sterile alginate or with the non encapsulated vaccine strain. Serum, urine, and semen samples were collected during two months after immunization. The rams were then challenged with wild type B. ovis (ATCC25840), and the results were compared to non immunized and experimentally challenged rams. Immunization, particularly with encapsulated B. ovis ΔabcBA, prevented infection, secretion of wild type B. ovis in the semen and urine, shedding of neutrophils in the semen, and the development of clinical changes, gross and microscopic lesions induced by the wild type B. ovis reference strain. Collectively, our data indicates that the B. ovis ΔabcBA strain is an exceptionally good vaccine strain for preventing brucellosis caused by B. ovis infection in rams.

During pharmaceutical lyophilization processes, inter-vial drying heterogeneity remains a significant obstacle. Due to differences in heat and mass transfer based on vial position within the freeze drier, edge vials freeze differently, are typically warmer and dry faster than center vials. This vial position-dependent heterogeneity within the freeze dryer leads to tradeoffs during process development. During primary drying, process developers must be careful to avoid shelf temperatures that would result in overheating of edge vials causing the product sublimation interface temperature to rise above the critical (collapse) temperature. However, at lower shelf temperatures, center vials require longer to complete primary drying, risking collapse or melt-back due to incomplete drying. Both situations may result in poor product quality affecting drug stability, activity, and reconstitution times. We present a new approach for monitoring vial location-specific water vapor mass flow based on Tunable Diode Laser Absorption Spectroscopy (TDLAS). The single vial monitor enables measurement of the gas flow velocity, water vapor temperature, and gas concentration from the sublimating ice, enabling the calculation of the mass flow rate which can be used in combination with a heat and mass transfer model to determine vial heat transfer coefficients and product resistance to drying. These parameters can in turn be used for robust and rapid process development and control., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progression. The aim of our study was to characterize the diffuse microglia activation in periplaque white matter (PPWM) of MS patients, to identify factors modulating its extent and to determine its potential correlation with loss or preservation of oligodendrocytes. We analyzed microglial and oligodendroglial numbers in PPWM in a cohort of 96 tissue blocks from 32 MS patients containing 100 lesions as well as a control cohort (n = 37). Microglia activation in PPWM was dependent on patient age, proximity to lesion, lesion type, and to a lesser degree on sex. Oligodendrocyte numbers were decreased in PPWM; however, increased microglia densities did not correlate with lower oligodendroglial cell counts, indicating that diffuse microglia activation is not sufficient to drive oligodendroglial loss in PPWM. In summary, our findings support the notion of the close relationship between focal and diffuse inflammation in MS and that age is an important modulator of MS pathology., (© 2023. The Author(s).)

As the most abundant renewable aromatic polymer on the planet, lignin is gaining growing interest in replacing petroleum-based chemicals and products. However, only <5 % of industrial lignin waste is revalorized in its macromolecular form as additives, stabilizing agents or dispersant and surfactants. Herein, revalorization of this biomass was achieved by implementing an environmentally-friendly continuous sonochemical nanotransformation to obtain highly concentrated lignin nanoparticles (LigNPs) dispersions for added-value material applications. With the aim to further model and control a large-scale ultrasound-assisted lignin nanotransformation, a two-level factorial design of experiment (DoE) was implemented varying the ultrasound (US) amplitude, flow rate, and lignin concentration. Size and polydispersity measurements together with the UV-Vis spectra of lignin recorded at different time intervals of sonication allowed to monitor and understand the sonochemical process on a molecular level. The light scattering profile of sonicated lignin dispersions showed a significant particle size reduction in the first 20 min, followed by moderate particle size decrease below 700 nm until the end of the 2 h process. The response surface analysis (RSA) of the particle size data revealed that the lignin concentration and sonication time were the most important factors to achieve smaller NPs. From a mechanistic point of view, a strong impact of the particle-particle collisions due to sonication seems to be responsible for the decrease in particle size and homogenization of the particle distribution. Unexpectedly, a strong interaction between the flow rate and US amplitude on the particle size and nanotransformation efficiency was observed, yielding smaller LigNPs at high amplitude and low flow rate or vice versa. The data derived from the DoE were used to model and predict the size and polydispersity of the sonicated lignin. Furthermore, the use of the NPs spectral process trajectories calculated from the UV-Vis spectra showed similar RSA model as the dynamic light scattering (DLS) data and will potentially allow the in-line monitoring of the nanotransformation process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Patients with bariatric surgery often show poor long-term compliance to recommendations for prevention of nutrient deficiency but it is unclear which factors contribute. We investigated the associations of age, sex, and socioeconomic status (SES) with adherence to guideline recommendations on protein intake and micronutrient supplementation., Methods: In a monocentric cross-sectional study we prospectively recruited patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) and a minimum postoperative period of 6 months. Clinical and demographic data were obtained from the patients' medical files and by questionnaire. Patients reported on supplement usage, recorded their dietary intake for seven days and underwent physical examinations including blood testing., Results: We included 35 patients (SG: n = 25, RYGB: n = 10) with a mean (+SD) postoperative period of 20.2 (±10.4) months. Distributions of age, sex and SES were comparable between the SG and RYGB groups. Non-adherence to recommended protein intake was associated with age ≥ 50 years (p = 0.041) but not sex or SES. Protein intake inversely correlated with markers of obesity. There were no significant associations of age or sex with micronutrient supplementation. Only for vitamins A (p = 0.049) and B1 (p = 0.047) higher SES was associated with greater compliance. The only manifest deficiency associated with non-adherence to micronutrient supplementation was that for folic acid (p = 0.044)., Conclusion: In patients after bariatric surgery, those of older age and of lower SES might have a greater risk of unfavorable outcome and may require greater attention to micronutrient and protein supplementation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wiese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Disseminated Intravascular Coagulation (DIC) is a life-threatening complication of sepsis. In surgical ICUs, DIC is frequently caused by abdominal sepsis, and the disarranged coagulation and complications often lead to death. The severity of sepsis is associated with a higher DIC score according to the parameters proposed by the International Society of Hemostasis and Thrombosis (ISTH) in 2001: platelet count, bleeding time (Quick), D-dimer, and fibrinogen. One problem in studying DIC is finding an adequate animal model that reflects the clinical situation of polymicrobial overwhelming infection., Aims and Methods: We investigated whether a well-established polymicrobial sepsis model of colon ascendens stent peritonitis (CASP) is suited to investigate the complexity of DIC. For this purpose, CASP-operated mice were examined 20 h after the operation with regard to coagulation parameters using cell counts, bleeding times, rotational thromboelastometry (ROTEM), ELISAs for D-dimer and fibrinogen, and platelet accumulation in affected organs via immunohistochemistry to see if the mice develop a coagulation disorder that meets the definition of DIC proposed by the ISTH 2001 consensus conference., Results: Herein, we showed that the CASP model is an all-encompassing animal model to analyze the complexity of systemic DIC in murine abdominal sepsis. There is highly reproducible thrombocytopenia, a significant prolongation of the bleeding time, and a loss of fibrinogen in plasma. We also observed microvascular thrombosis due to platelet accumulation in the microcirculation of the liver., Conclusion: The CASP model seems superior to other artificial models, e.g., injecting substances, for inducing DIC. CASP is one of the best true-to-life models for analyzing the complexity of disseminated intravascular coagulation in polymicrobial sepsis., Competing Interests: NO - The authors have declared that no competing interests exist., (Copyright: © 2022 van der Linde et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Barrett's esophagus (BE) and dysplasia are often missed by Seattle protocol biopsies (SPB). Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS-3D) with SPB improves detection in treatment-naïve patients. We aimed to determine to what extent WATS-3D adds to SPB in the detection of non-dysplastic BE (NDBE) and dysplasia in patients undergoing post-endoscopic eradication therapy (EET)., Methods: This retrospective, observational, cross-sectional study included patients who presented for post-EET surveillance with SPB and WATS-3D sampling from April 2019 to February 2020. BE patients with no previous EET were excluded. For the outcomes of NDBE and any dysplastic/neoplastic finding, we calculated both relative and absolute increases in yield by WATS-3D over SBP., Results: In 78 patients [mean age 68±10.4 years, 66 (84.6%) male], the prevalence of NDBE, any dysplastic/neoplastic finding, and any abnormality (NDBE or dysplasia/neoplasia) were 53.85%, 10.26%, and 55.13%. The absolute increase in yield of NDBE with WATS-3D over SPB was 26.9% (95% confidence interval [CI] 17.95-37.18%), with the number needed to treat (NNT) 3.71 (95%CI 2.69-5.57) and a relative increase in yield of 100% (95%CI 53.33-188.25%). For dysplasia/neoplasia, the absolute increase in yield was 6.4% (95%CI 1.28-12.82%), NNT 15.6 (95%CI 7.8-78.0), and relative increase of 167% (95%CI 33.33%-infinity). For any abnormal finding, the absolute increase in yield was 26.9% (95%CI 16.67-37.18%), NNT 3.71 (95%CI 2.69-6.00), and relative increase in yield 95% (95%CI 50-176.92%)., Conclusions: WATS-3D with SPB improves the detection of residual/recurrent BE and dysplasia in post-ablation BE. However, randomized controlled trials are needed to validate these findings., Competing Interests: Conflict of Interest: John Dewitt: Research grant: Vyaire Medical; Consultant: Boston Scientific and Cook Medical., (Copyright: © Hellenic Society of Gastroenterology.)

Inherited thrombophilia is an important cause of venous thrombosis. The Factor V Leiden (FVL) is the most commonly encountered mutation, followed by the prothrombin G20210A gene mutation (PTM). The typical venous thrombotic events (VTEs) associated with PTM mutations are deep vein thrombosis (DVT) and pulmonary embolisms (PE). The PTM is inherited in an autosomal dominant pattern with variable penetrance. While heterozygous PTM mutations are more frequent and well documented in the literature, rare cases of homozygous PTM mutations are also reported. In this report, we discuss a 56-year-old male with a past medical history of homozygous prothrombin gene mutation (G20210A) who presented with an unprovoked DVT of the right lower extremity involving both the proximal and distal veins associated with multiple bilateral PEs. This case is unique in terms of the homozygous PTM inheritance, the age at which the patient presented (usually presentation is earlier in life), and the fact that he had a recurrence of both DVT and PE simultaneously.

Introduction: Adiposity and excessive weight are on the rise in western industrialized countries. In cases where conservative measures fail and surgical interventions are not (yet) desired, gastric balloon therapy has proven to be a safe and reversible endoscopic method., Methods: Aside from weight progression under gastric balloon therapy and by using MRI, our research paper describes the behavior of different abdominal body fat compartments at the beginning and at the end of the gastric balloon therapy. Additionally, the volume of the left liver lobe as well as the fill volume and performance of the gastric balloon were analyzed over the duration of treatment. For assessing potential impacts of weight reduction on the muscle mass, we determined the area of the m. psoas on a comparable cross-sectional area at the beginning and at the end of the therapy., Results: We were able to verify a significant reduction of the layer of subcutaneous fat, adipose capsule of the kidney, and intra-abdominal fatty tissue during the therapy. The volume of the left liver lobe was shrinking in addition to a muscle loss during the balloon therapy. The volume of the gastric balloon remained stable (not hyperinflation). There were variable gas bubbles in the gastric balloon., Conclusion: The gastric balloon is a temporary and successful option for weight reduction by reducing body fat, liver volume, but also muscle mass., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

This work presents a compact model for the equipment capability limit of a common configuration of pharmaceutical lyophilizers, a product chamber separated from the condenser by a duct and isolation valve, at a wide range of design parameters. The equipment capability limit is one of the most important characteristics determining the lyophilization design space for a particular product, container, and equipment combination. Experimental measurements of equipment capability are time-consuming and expensive, especially at the production scale. Numerical modeling using computational fluid dynamics may reduce the number of experiments and provide insights into the physics of the process with high resolution. The computational fluid dynamics (CFD) modeling has been used in this work to develop a compact model for lyophilizer equipment capability. This eliminates the need for end users to create a full CFD model of the equipment and process. Full CFD and compact model simulations for laboratory and pilot-scale lyophilizers have been compared with tunable diode laser absorption spectroscopy measurements of the water vapor mass flow during ice slab tests. The compact model results average deviation from the experimental data is within 10%, whereas the full CFD simulations are within 5%. The compact model is based on several key parameters which are the main characteristics of a lyophilizer affecting the equipment capability curve. These parameters are discussed, and their effect on the modeling results is shown., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Freeze-drying is a deceptively complex operation requiring sophisticated design of a robust and efficient process that includes understanding and planning for heterogeneity across the batch and shifts in parameters due to vial or lyophilizer changes. A software tool has been designed to assist in process development and scale-up based on a model that includes consideration of the process heterogeneity. Two drug formulations were used to test the ability of the new tool to develop a freeze-drying cycle and correctly predict product temperatures and drying times. Model inputs were determined experimentally, and the primary drying heterogeneous freeze-drying model was used to design drying cycles that provided data to verify the accuracy of model-predicted product temperature and primary drying time. When model inputs were accurate, model-predicted primary drying times were within 0.1 to 15.9% of experimentally measured values, and product temperature accuracy was between 0.2 and 1.2°C for three vial locations, center, inner edge, and outer edge. However, for some drying cycles, differences in vial heat transfer coefficients due to changes in shelf and product temperature as well as altered product resistance due to product temperature-dependent microcollapse increased inaccuracy (up to 28.6% difference in primary drying time and 5.1°C difference in product temperature). This highlights the need for careful determination of experimental conditions used to calculate model inputs. In future efforts, full characterization of location- and shelf temperature-dependentK v as well as location- and product temperature-dependentR p will enhance the accuracy of the predictions by the model within the user-friendly software., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test-retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.

Purpose: The implantation of a gastric balloon (also known as intragastric balloon) is an established and reversible endoscopic procedure for adiposity therapy. Structural changes of the stomach wall are expected to occur with gastric balloon implantation; however, until now these changes have rarely been investigated., Methods: We compared the histological structure of the stomach wall after gastric-sleeve resection in a group of patients following gastric balloon implantation and a group without previous gastric balloon implantation., Results: Following gastric balloon implantation, the tunica muscularis was found to be significantly thicker than without gastric balloon implantation. The enlarging of the tunica muscularis is not caused by hyperplasia of the leiomyocytes, but by hypertrophy of the leiomyocytes and an increase in collagen fibers (fibrosis)., Conclusion: A longer-lasting hypertrophy of the tunica muscularis, particularly in the corpus, should be taken into account when surgical treatment follows gastric balloon implantation. The staple suture height should be adjusted to the altered tissue composition since reduced tissue elasticity must be expected due to fibrosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Melamine-formaldehyde (MF) resins are widely used as surface finishes for engineered wood-based panels in decorative laminates. Since no additional glue is applied in lamination, the overall residual curing capacity of MF resins is of great technological importance. Residual curing capacity is measured by differential scanning calorimetry (DSC) as the exothermic curing enthalpy integral of the liquid resin. After resin synthesis is completed, the resulting pre-polymer has a defined chemical structure with a corresponding residual curing capacity. Predicting the residual curing capacity of a resin batch already at an early stage during synthesis would enable corrective measures to be taken by making adjustments while synthesis is still in progress. Thereby, discarding faulty batches could be avoided. Here, by using a batch modelling approach, it is demonstrated how quantitative predictions of MF residual curing capacity can be derived from inline Fourier Transform infrared (FTIR) spectra recorded during resin synthesis using partial least squares regression. Not only is there a strong correlation (R 2 = 0.89) between the infrared spectra measured at the end of MF resin synthesis and the residual curing capacity. The inline reaction spectra obtained already at the point of complete dissolution of melamine upon methylolation during the initial stage of resin synthesis are also well suited for predicting final curing performance of the resin. Based on these IR spectra, a valid regression model (R 2 = 0.85) can be established using information obtained at a very early stage of MF resin synthesis.

Reactive thrombocytosis after splenectomy is a feared cause of thrombosis throughout the arterial and venous system. There are many causes of splenomegaly, ranging from cirrhosis to lymphoma to hereditary spherocytosis. In this report, we will discuss a case of reactive thrombocytosis after splenectomy in a patient with hereditary spherocytosis. Splenomegaly is a relatively common finding in HD patients, causing extravascular haemolysis and thus leading to haemolytic anaemia. Splenectomy is usually considered when patients start to manifest severe symptoms such as abdominal pain, jaundice or worsening liver function tests. Our patient was a good surgical candidate and successfully underwent splenectomy but afterwards developed arterial and venous thrombosis due to reactive thrombocytosis. An extensive hypercoagulable work-up was unremarkable. The patient was started on hydroxyurea and anticoagulation with eventual improvement of platelet levels., Learning Points: Reactive thrombocytosis can be a significant complication after splenectomy and can range from mild (500,000-700,000/mm 3 ), to moderate (700,000-900,000/mm 3 ), severe (>900,000/mm 3 ) and very severe thrombocytosis (>1,000,000/mm 3 ).The use of low-dose hydroxyurea in patients with very severe thrombocytosis can reduce the platelet count to safe levels, and thus, the risk of developing thrombosis., Competing Interests: Conflict of interests: The authors declare there are no competing interests., (© EFIM 2021.)

Here, we study resin cure and network formation of solid melamine formaldehyde pre-polymer over a large temperature range via dynamic temperature curing profiles. Real-time infrared spectroscopy is used to analyze the chemical changes during network formation and network hardening. By applying chemometrics (multivariate curve resolution, MCR), the essential chemical functionalities that constitute the network at a given stage of curing are mathematically extracted and tracked over time. The three spectral components identified by MCR were methylol-rich, ether linkages-rich and methylene linkages-rich resin entities. Based on dynamic changes of their characteristic spectral patterns in dependence of temperature, curing is divided into five phases: (I) stationary phase with free methylols as main chemical feature, (II) formation of flexible network cross-linked by ether linkages, (III) formation of rigid, ether-cross-linked network, (IV) further hardening via transformation of methylols and ethers into methylene-cross-linkages, and (V) network consolidation via transformation of ether into methylene bridges. The presented spectroscopic/chemometric approach can be used as methodological basis for the functionality design of MF-based surface films at the stage of laminate pressing, i.e., for tailoring the technological property profile of cured MF films using a causal understanding of the underlying chemistry based on molecular markers and spectroscopic fingerprints.

In Ukraine, a retrospective review of clinical case reports by public health officials suggest that human cases of febrile illnesses associated with hemorrhage may be due to infections of Crimean-Congo hemorrhagic fever virus (CCHFV) and Old World hantaviruses. In a serosurvey of 966 healthy individuals in the Lviv Oblast, Ukraine, bordering Poland, we found that 1.6% showed cross-reactivity to hantaviral antigens by an immunofluorescence assay (IFA) and 1.7% of the study participants had antibodies cross-reactive to CCHFV by enzyme-linked immunosorbent assay (ELISA). Demographic variables and history of exposures obtained through questionnaires were assessed by logistic regression models for association with seroprevalence for both viruses with no significant risk factors found. Analysis of spatial distribution identified two clusters of samples positive for antibodies to both hantaviruses and CCHFV, which, however, were not statistically significant (p > 0.05). In general, the study results suggest that the population of the study area is exposed to hantaviruses and CCHFV. Further surveillance for respective pathogens in Ukraine is warranted and prospective surveillance of febrile patients with unidentified febrile illness., (Copyright © 2020 Lozynskyi, Shulgan, Zarichna, Ben, Kessler, Cao, Nesterova, Glass, Spruill-Harrell, Taylor, Williams and Jonsson.)

Introduction: Precisely locating benign upper gastrointestinal tumors during laparoscopic-endoscopic surgery remains difficult and inaccurate. We describe reverse laser-supported diaphanoscopy (RLSD) for locating gastrointestinal tumors during laparoscopic surgery and present prospective evaluation results of the first cases., Materials and Methods: We studied 13 patients [women:men=7:6; mean age, 67 (range, 41 to 83) y] who underwent gastroscopic-laparoscopic rendezvous procedures during 2015 to 2018. Surgery duration, marking duration, and specimen resection size were recorded. The largest and smallest specimen resection margins were measured., Results: After locating tumors using RLSD, patients underwent successful resections. Histopathologic examination confirmed 5 cases of gastrointestinal stromal tumor; 3, neuroendocrine tumors; 2, heterotopic pancreatic tissue; 1, leiomyoma; 1, adenoma; 1, hyperplastic polyp. We employed 4 to 6 marks, depending on tumor location and size. The average marking duration was 14 minute (1 to 21 min); the average surgery duration, 73 minute (37 to 143 min). The smallest resection median margin was 2.0 mm (1.0 to 5.0 mm); the largest, 7.0 mm (2.0 to 12.0 mm)., Conclusions: RLSD precisely locates gastric benign tumors during laparoscopic-endoscopic rendezvous procedures.