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In 2022, two independent insect surveys in canton Ticino (southern Switzerland) revealed the widespread occurrence of the invasive ambrosia beetleAnisandrus maichefrom southern to central-upper Ticino. This species is native to east Asia and has previously been found as a non-native invasive species in the United States, Canada, western Russia, Ukraine and, in 2021, in northern Italy. Here, we present the results of several trapping studies using different trap types (bottle traps, funnel traps and Polytrap intercept traps) and attractants and a map of the distribution of the species. In total, 685 specimens ofA. maiche, all female, were trapped, and the identity of selected individuals was confirmed by morphological and molecular identification based on three mitochondrial and nuclear markers (COI, 28S and CAD). Traps checked from early April to early September 2022 in intervals of two to four weeks showed that flights ofA. maicheoccurred mainly from June to mid-August. Isolation of fungal associates ofA. maichefrom beetles trapped alive revealed the presence of four fungal species, including the ambrosia fungusAmbrosiella cleistominuta, the known mutualists ofA. maiche. The identity ofA. cleistominutawas confirmed by comparing DNA sequences of its nuclear, internal transcribed spacer (ITS) gene with reference sequences in NCBI and BOLDSYSTEMS. This represents the first record ofA. cleistominutain Europe.Ambrosiella cleistominutawas also found in association with another non-native invasive ambrosia beetle,Xylosandrus crassiusculus, at a botanic garden in central Ticino. As ambrosia beetles usually show a high degree of fidelity with only one mutualistic fungus (in the case ofX. crassiusculusnormallyAmbrosiella roeperi), this association is highly unusual and probably the result of lateral transfer among these non-native invasive species. Of the other fungal associates isolated fromA. maichein Ticino,Fusarium lateritiumis of note as there is a possibility thatA. maichecould act as a vector of this plant pathogen. We highlight several research needs that should be addressed to gain insight into the potential impact of these non-native species and to overcome problems with heteroplasmy in COI sequences in studies of invasion and population genetics of ambrosia beetles.

ZusammenfassungDer Versicherungsvertrieb umfasst aus regulatorischer Sicht neben den selbstständigen Versicherungsvermittlern auch viele Versicherungsbeschäftigte. Er gehört zu den operationellen Risiken eines Versicherers. Spezifische Vertriebsrisiken resultieren aus der Zusammenarbeit mit Vermittlern, aus den typischen Vergütungs- und Anreizgestaltungen sowie aus Beratung, Information, Betreuung und Schadenregulierung gegenüber den Kundinnen und Kunden. Vertriebsrisiken können vor allem durch organisatorische Maßnahmen gemindert und begrenzt werden.

This study investigated the effects of injectable vitamin C (VC) at weaning and prior to transit on growth performance and immune function in early-weaned beef steers. On day 0, 91 Angus × Simmental steers (92 ± 4 kg) were weaned (65 ± 11 d of age), given vaccination boosters, blocked by age, and randomly assigned to weaning (WEAN) treatments: intramuscular injections (20 mL per steer) of VC (250-mg sodium ascorbate per mL; 5 g per steer) or saline (SAL). From days 0 to 48, steers were housed at the Dixon Springs Agricultural Center (Simpson, IL) in pens (six pens; N = 14 to 16 steers per pen) equipped with two to three Vytelle bunks to measure individual daily feed disappearance. On day 49, half of the steers in each WEAN treatment were randomly assigned to an additional injection treatment (20 mL per steer) of VC or SAL prior to transport (TRANS). After administering pretransit injections, all steers were loaded onto a commercial livestock trailer with equal representation of treatments across compartments. Steers were transported for 6 h (approximately 480 km) to the Illinois Beef and Sheep Field Laboratory (Urbana, IL). Upon arrival, steers were sorted into pens (six pens; N = 13 to 17 steers per pen) with 2 Vytelle bunks per pen. Steers were weighed on days 0, 1, 14, 48, 49, 64, 78, 106, and 107. Blood was collected (WEAN = 24 steers per treatment; TRANS = 12 steers per treatment) on days 0, 1, 2, 14, 49 (pre- and posttransit), 50, and 51. Data were analyzed using the MIXED procedure of SAS 9.4 with fixed effects of age block, WEAN, TRANS, and WEAN × TRANS. Plasma ascorbate concentrations were greater (WEAN × time P0.01) on days 1 and 2 for steers that received VC at weaning. Similarly, for steers that received VC on day 49 pretransit, ascorbate concentrations were greater (TRANS × time P = 0.04) on days 49 posttransit, 50, and 51. Treatments did not affect (P ≥ 0.13) body weight, average daily gain, or gain to feed throughout the trial. Serum Bovine Viral Diarrhea Virus type 1 and 2 antibody titers on days 14 and 51 were not affected (P ≥ 0.32) by treatment. Injectable VC administered to early-weaned beef steers at the time of weaning or pretransit increased plasma ascorbate concentrations but did not improve growth performance or antibody response to vaccination booster.Weaning and transit represent the primary stressors for beef calves in the United States and are responsible for increasing inflammation, suppressing the immune system, and decreasing antioxidant status. These adverse physiological responses to stressors may decrease growth and increase morbidity in beef calves. Vitamin C is the primary water-soluble antioxidant in plasma and when provided intramuscularly prior to the stress event, may be able to attenuate aspects of a stress response on growth and immune function. This study evaluated the effects of injectable vitamin C given to early-weaned beef calves prior to weaning on day 0 and a 6-h transit on day 49 after weaning. Basal levels of plasma ascorbate were lower than prior studies in older and larger animals. As expected, injectable vitamin C rapidly increased plasma ascorbate concentrations at 24 h, but concentrations also increased in control calves receiving a saline injection. Treatments did not affect overall growth performance or dry matter intake. Treatments also did not impact the immune response to a booster vaccination provided at weaning. While other research has indicated a positive effect of injectable vitamin C prior to transit, additional research is needed to refine the dosage and physiological need for exogenous antioxidants like vitamin C based on the severity and duration of a stress event in lightweight beef calves.

Glioblastoma (GBM), with its very poor prognosis, accounts for 57% of gliomas and 48% of malignant central nervous system (CNS) tumors. After standard therapy, patients with GBM usually die within six months. The case of an adult male with a newly-diagnosed GBM is presented here to detail/discuss the efficacy of ANP therapy (Antineoplaston A10 {Atengenal} and Antineoplaston AS2-1 {Astugenal}) in the treatment of GBM and to permit a review of the Phase II Protocol BT-07. Objectives: This patient was treated at the Burzynski Clinic (BC), according to the Phase II Protocol, BT-07, which utilized IV ANP therapy in the treatment of patients with newly-diagnosed GBMs. ANP therapy was delivered via subclavian catheter and infusion pump. Tumor response was measured by sequential magnetic resonance imaging (MRI) of the brain utilizing gadolinium enhancement. Findings: At age 37, this patient was diagnosed with GBM of the right frontal lobe after subtotal tumor resection performed elsewhere. At age 37 years and six months, he presented to the BC with this newly diagnosed disease. He had a recent history of forgetfulness and personality change. Neurologic examination was otherwise normal. Baseline brain MRI at the BC revealed a measurable enhancing nodule (4.0 cm x 2.0 cm) in the right frontal lobe. Intravenous (IV) ANP therapy began in November 1995 and a partial response (PR) was achieved within three months. After another 5 months of IV ANP therapy, the patient underwent a complete tumor resection, then additional ANP therapy. Now, > 27 years later, the patient is doing well and showing no evidence of tumor recurrence. Conclusions: The utilization of ANP therapy to facilitate a cure in a patient with newly-diagnosed GBM is presented. We conclude that ANP therapy is an attractive therapeutic option for adults with a GBM who are ineligible for or refuse standard therapy.

We previously demonstrated that MgrA, SarA, SarR, SarS, SarZ, and Rot bind at least three of the four promoters associated with genes encoding primary extracellular proteases inStaphylococcus aureus. We also showed that mutation ofsarAresults in a greater increase in protease production, and decrease in biofilm formation, than mutation of the loci encoding any of these other proteins. However, these conclusions were based onin vitrostudies. Thus, the goal of the experiments reported here was to determine the relative impact of the regulatory loci encoding these proteinsin vivo. To this end, we compared the virulence ofmgrA, sarA, sarR, sarS, sarZ, androtmutants in a murine osteomyelitis model. Mutants were generated in the methicillin-resistant USA300 strain LAC and the methicillin-sensitive USA200 strain UAMS-1. As assessed based on an overall osteomyelitis pathology score derived from the incidence of bone fracture, bacterial burdens in the bone, cortical bone destruction, and reactive bone formation, mutation ofmgrAandrotlimited virulence to a statistically significant extent in UAMS-1, but not in LAC. In contrast, thesarAmutant exhibited reduced virulence in both strains. This illustrates the importance of considering diverse clinical isolates when evaluating the impact of regulatory mutations on virulence. The reduced virulence of thesarAmutant was correlated with reduced cytotoxicity for osteoblasts and osteoclasts, reduced biofilm formation, and reduced sensitivity to the antimicrobial peptide indolicidin, all of which were directly attributable to increased protease production in both LAC and UAMS-1. This suggests that thesein vitrophenotypes, either alone or in combination with each other, may be useful in prioritizing additional mutants forin vivoevaluation. Most importantly, they illustrate the significance of limiting protease productionin vivoin S.aureus, and confirm that SarA plays the primary role in this regard.Author SummaryStaphylococcus aureuscauses a diverse array of infections due to its ability to produce an arsenal of virulence factors. Among these are extracellular proteases, which serve several purposes on behalf of the bacterium. However, it has become increasingly apparent that it is also critical to limit the production of these proteases to prevent them from compromising theS. aureusvirulence factor repertoire. Many regulatory loci have been implicated in this respect, but it is difficult to draw relative conclusions because few reports have made direct comparisons, and fewer still have done soin vivo. We addressed this by assessing the impact on virulence of six regulatory loci previously implicated in protease production. We did this in the clinical context of osteomyelitis using mutants generated in two divergent clinical isolates. Our results confirm significant strain-dependent differences, reinforcing the importance of considering such diverse clinical isolates when evaluating targets for potential therapeutic intervention. In this respect, only mutation ofsarAattenuated virulence in both strains. This illustrates the importance of limiting protease production as a means of post-translational regulatory control inS. aureusand confirms thatsarAplays a predominant role in this regard.

The fungal pathogens of spruce are well known in Europe and elsewhere. Therefore, it was surprising to discover a new fungal species and genus in Central Europe that attacks the pollen cones of three spruce species. The new ascomycete forms apothecia on stromatized pollen cones of Norway spruce (Picea abies) and Serbian spruce (Picea omorika) in mountain areas and on West Himalayan spruce (Picea smithiana) planted in urban lowland regions of Switzerland, Germany, and Italy. It was also detected in France, based on metabarcode sequences deposited in the GlobalFungi database. Its sudden appearance and the different origins of the host trees in Europe and Asia leave the origin of the fungus unclear. The new fungus might be a neomycete for Europe. A phylogenetic analysis using SSU, LSU, ITS, RPB2, and TEF1 sequences classified the fungus as a member of Sclerotiniaceae (Helotiales, Leotiomycetes). However, it differs morphologically from the other genera of this family in having an ascus without apical apparatus containing four mainly citriform spores with 16 nuclei each. Furthermore, it is the only known cup fungus that parasitizes pollen cones of conifers by stromatizing their tissue and infecting pollen grains. The fungus does not seem to cause major damage to the spruce populations, as only a few pollen cones per tree are affected. All this leads us to describe the newly discovered fungus as the new species and new genus Microstrobilinia castrans, the fungus that castrates pollen cones of spruce.

The objectives were to assess the effects of dietary Sweet Bran (Cargill Corn Milling, Blair, NE) on performance and feeding behavior of feedlot steers and determine if terminal implant pen sorting affects performance, feeding behavior, and liver abscess (LA) rate. Two hundred sixteen Angus-cross steers (253 ± 18 kg) were stratified by body weight (BW) to 36 pens. From d 0 to 60, diets contained 40% Sweet Bran (SWBR) or 25% modified distiller’s grains and 15% dry rolled corn (MOD; n = 18 pens/treatment). On d 60, steers began transition within treatments to finishing diets containing 25% Sweet Bran or 25% modified distiller’s grains (MDGS). On d 111, half of the pens for each dietary treatment were re-stratified by BW to pens (SORT) while the other half were returned to original pens (NOSORT; n = 9 pens/treatment). Steer BW and pen dry matter intake (DMI) were recorded monthly. Rate of feed disappearance was determined on d 5/6, 53/54, 104/105, and 117/118. Pen was the experimental unit for all analyses. The model included the fixed effect of diet for all pre-sort analyses; post-sort analyses included the fixed effects of diet, sort, and the interaction and the random effects of pen and the interaction of diet and pen. On d 60, SWBR had greater BW than MOD (P = 0.05), and SWBR had a greater average daily gain (ADG) from d 0 to 60 (P = 0.05). Though there were no differences after d 28, SWBR had greater DMI d 0 to 28 (P = 0.05). From d 60 to 88, SWBR tended to have lesser ADG than MOD (P = 0.09). Post-sort (d 111 to 196), SWBR tended to have lesser ADG than MOD (P = 0.06), and SORT had a greater rate of feed disappearance than NOSORT (d 117/118; P = 0.01); there were no differences on other dates (Diet: P ≥ 0.38). For final BW, there was a tendency for MOD to be greater than SWBR, and SORT tended to be greater than NOSORT (Diet: P = 0.06; Sort: P = 0.10). Pre- and post-sort ruminal pH had no treatment by day differences (P ≥ 0.77). LA incidence averaged 25%, though rate was not affected by diet, sorting, or the interaction (P ≥ 0.16). Overall, there were no dietary differences in feed disappearance rates, though SORT steers had greater rate of feed disappearance than NOSORT steers on d 117/118. Nominal differences in feeding behavior were noted and including Sweet Bran in the diet was beneficial in the growing period as cattle adjusted to the feedlot.

The objective was to determine the effects of injectable vitamin E (VE) before or after transit on feedlot cattle receiving performance, health, and blood parameters. Angus × Simmental steers (n = 196; body weight [BW] = 163 ± 29 kg) were utilized in a randomized complete block design. Steers were blocked by BW and randomly assigned to 1 of 3 treatments: intramuscular injections of saline pre- and post-transit (CON), intramuscular injections of VE (2,000 mg d-α-tocopherol) pre-transit and saline post-transit (PRE), or intramuscular injections of saline pre-transit and VE (2,000 mg d-α-tocopherol) post-transit (POST). Pre-transit injections were administered on day 0, and steers were transported on day 7 for approximately 4 h (348 km). After arrival, steers were fed a common corn silage-based diet in GrowSafe bunks. Final BW tended to be greater (P = 0.08) for CON steers compared with POST steers while PRE steers were intermediate. From days 7 to 63, treatment affected average daily gain (ADG) with PRE and CON steers exhibiting (P = 0.04) greater ADG compared with POST steers. Dry matter intake (DMI), water intake, and gain to feed from days 7 to 63 were not affected (P ≥ 0.17) by treatment. Day 0 serum α-tocopherol concentrations were considered marginal (2.3 ± 0.2 mg/l). A treatment × day interaction (P0.01) was observed for serum α-tocopherol concentrations. Serum α-tocopherol concentrations were greatest for PRE steers on day 7 (prior to and post-transit), but greater for POST steers on dys 10 and 14. Plasma ferric-reducing antioxidant potential concentrations increased (P = 0.04) for POST steers compared with CON steers and PRE steers being intermediate. Plasma non-esterified fatty acids (NEFA) concentrations exhibited a treatment × day interaction (P = 0.04) with CON and POST steers being 16% and 14% greater than PRE steers on day 14, respectively. On day 21, NEFA concentrations were greatest for POST steers compared with PRE steers and CON steers being intermediate. There was no main effect (P ≥ 0.14) of treatment on the number of bovine respiratory disease morbidity treatments. Hair cortisol concentrations were decreased (P0.01) 14 days after transit for PRE and POST steers compared with CON steers. Overall, injectable VE administered before or after transit increased serum tocopherol concentrations while reducing stress, but did not improve the growth performance of beef steers during the receiving phase.Cattle are transported multiple times throughout their lifespan due to the geographic distribution of the United States beef industry. However, transportation can elicit a variety of stressors that jeopardize cattle growth performance and health. Lightweight feeder calves are at the greatest risk for stress-related morbidity and mortality during the feedlot receiving phase. This study evaluated the effects of injectable vitamin E (VE) before or after transit on feedlot receiving phase growth performance, health, and blood parameters of lightweight beef steers. Steers receiving an injection of VE before or after transit had increased serum α-tocopherol concentrations. However, treatment with VE did not improve growth performance and feed intake. Steers injected with VE before or after transit experienced a decrease in hair cortisol concentrations 14 d after transit while steers injected with VE after transit had improved antioxidant status 14 d after transit compared with control steers and those receiving VE before transit. These results indicate that an injection of VE around the time of transit had no effect on growth performance and intake but can improve antioxidant status during the receiving phase.

Antibiotic-loaded chitosan pastes have shown advantages in treatment and coverage of complex musculoskeletal defects. We added mannitol, previously shown to increase antibiotic susceptibility of biofilm, to an injectable chitosan/polyethylene glycol paste for delivery of antibiotics. Ground sponges (0.85% acetic acid solution, 1% chitosan, 0% or 2% mannitol, 1% polyethylene glycol) were hydrated using phosphate buffered saline with 10 mg/ml amikacin and 10 mg/ml vancomycin added to form pastes. We inoculated rabbit radial defects with 105 colony forming units of Staphylococcus aureus (UAMS-1) and inserted titanium pins into cortical bone. Groups compared included mannitol blend pastes, non-mannitol blends, antibiotic-loaded bone cement, vancomycin powder, and no treatment controls. We harvested tissue samples and retrieved the pins retrieved at 3 weeks. All antibiotic-loaded groups lowered bacterial growth and CFU counts in soft and bone tissue and on titanium pins in in vivo studies. Results indicate this biomaterial is capable of eluting active antibiotic at concentrations that reduce bacterial growth on biomaterials and tissue, which in turn may prevent biofilm formation. Blends of chitosan and mannitol may be useful in prevention and treatment of osteomyelitis and implant-associated infections. This article is protected by copyright. All rights reserved.

It is common knowledge that molecular energy level offsets of a type II heterojunction formed at the donor–acceptor interface are considered to be the driving force for photoinduced charge transfer in organic solar cells. Usually, these offsets – present between molecular energy levels of the donor and acceptor – are obtained via cyclic voltammetry (CV) measurements of organic semiconductors cast in a film or dissolved in solution. Simply transferring such determined energy levels from solution or film of single materials to blend films may be obviously limited and not be possible in full generality. Herein, we report various cases of material combinations in which novel non-fullerene acceptors did not yield successful charge transfer, although energy levels obtained by CV on constituting single materials indicate a type II heterojunction. Whilst the integer charge transfer (ICT) model provides one explanation for a relative rise of molecular energy levels of acceptors, further details and other cases have not been studied so far in great detail. By applying energy-resolved electrochemical impedance spectroscopy (ER-EIS) on several donor–acceptor combinations, a Fano-like resonance feature associated with a distinctive molecular energy level of the acceptor as well as various relative molecular energy level shifts of different kinds could be observed. By analyzing ER-EIS and absorption spectra, not only the exciton binding energy within single materials could be determined, but also the commonly unknown binding energy of the CT state with regard to the joint density of states (jDOS) of the effective semiconductor. The latter is defined by transitions between the highest occupied molecular orbitals (HOMO) of the donor and the lowest unoccupied molecular orbitals (LUMO) of the acceptor. Using this technique among others, we identified cases in which charge generation may occur either via uphill or by downhill processes between the charge transfer exciton and the electronic gap of the effective semiconductor. Exceptionally high CT-exciton binding energies and thus low charge generation yields were obtained for a case in which the donor and acceptor yielded a too intimate blend morphology, indicating π–π stacking as a potential cause for unfavorable molecular energy level alignment.

Introduction The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time. Methods To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort N = 426) entering an emergency department in New York City and subsequently admitted for inpatient care. Results Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (ρ = 0.732, P < .0001). Of the 14% of the cohort who met Acute Kidney Injury Network (AKIN) SCr criteria for acute kidney injury (AKI), 67% demonstrated transient (2 days) elevation of SCr. Comparing the outcomes of patients with sustained versus transient or undetectable changes in SCr revealed that the urinary NGAL (uNGAL) dipstick had high specificity and negative predictive value (NPV) (high- vs. low-intermediate readings, sensitivity = 0.55, specificity = 0.91, positive predictive value = 0.24, NPV = 0.97, χ2 = 20.39, P < 0.001). Conclusion We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr., Graphical abstract

We developed a quantum-chemical approach for ab initio calculations of metastable-induced electron-emission spectra (MIES). In contrast to earlier work, our calculation method accounts for the anisotropy of the MIES spectra with respect to not only the direction of incidence of metastable helium but also to that of electron detection. Since we can freely choose both, incidence and detection direction in our simulation, our method is able to reconstruct MIES spectra which are dominated by Auger deexcitation for any experimental setups and orientation of the studied molecules. Here, we study the dependence of the MIES spectrum on the incidence and detection direction and other experimental parameters and compare the results for the case of adsorbed benzene with experimental data.

The phylogenetic revision of the genera Petrakia and Seifertia using LSU, ITS, RPB2 and TEF1 sequences and the re-evaluation of their morphological characteristics lead to several reclassifications: The genus Pseudodidymella as well as the genera Mycodidymella and Xenostigmina are synonymized with the genus Petrakia. Based on ITS sequence comparisons, it was previously suspected that the leaf spot pathogen Pseudodidymella fagi, which occurs on the Japanese beech Fagus crenata in Japan, is conspecific to the pathogen attacking the European beech Fagus sylvatica in Switzerland and Germany since 2008. Herein, we show that Japanese and European collections represent separate species and describe the European one as Petrakia liobae new to science. Apart from that, we make the new combinations Petrakia fagi and Petrakia minima. The names Petrakia aesculi and Petrakia aceris are validated. A 60-year-old collection from Wisconsin USA, designated as Petrakia echinata on leaves of silver maple (Acer saccharinum), proved to be another species new to science and is described here as Petrakia greenei. Consequently, there is currently no evidence of the European P. echinata to occur in North America. In contrast, P. echinata was found to infect the North American big leaf maple (Acer macrophyllum) in Europe. Antromycopsis alpina, described in 1914, was rediscovered in the Swiss Alps from dry fruits of Rhododendron ferrugineum. It is combined in Seifertia as S. alpina, based on molecular phylogenetic and morphological analyses. This anamorphic fungus appears to be native to Europe and does not cause a bud disease on Rhododendron in contrast to the closely related S. azaleae. Seifertia shangrilaensis is the third species of this genus that is closely related to Petrakia. Both genera belong to the family Melanommataceae.

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created mice expressing Rosa26-floxed-stop uracil phosphoribosyltransferase (Uprt) and inoculated 4-thiouracil (4-TU) to tag nascent RNA at selected time points. Cre-driven 4-TU-tagged RNA was isolated from intact kidneys and demonstrated that volume depletion and ischemia induced different genetic programs in collecting ducts and intercalated cells. Even lineage-related cell types expressed different genes in response to the 2 stressors. TU tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa26 locus, nascent RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, 4-TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.

The objective of these experiments was to assess the effects of food and water deprivation and transit duration on the behavior of beef feedlot steers. In Experiment 1, 36 Angus-cross steers (353 ± 10 kg) were stratified to 6 pens and assigned one of three treatments (n = 12 steers per treatment): control (CON; stayed in home pens with ad libitum access to feed and water), deprived (DEPR; stayed in home pens but deprived of feed and water for 18 h), or transported (TRANS; subjected to 18-h transit event and returned to home pens). In Experiment 2, 60 Angus-cross steers (398 ± 5 kg; 6 steers per pen) were transported either 8 (8H) or 18 (18H) h. Four 8H pens (n = 24 steers) and six 18H pens (n = 36 steers) were used for behavioral analysis. In both experiments, the time to eat, drink, and lay down was recorded for each steer upon return to home pens. Total pen displacements from the feed bunk were also assessed for the 2 h following feed access in both experiments. Data were analyzed using Proc Mixed of SAS 9.4, with treatment as a fixed effect. Steer was the experimental unit for behavioral activities, while pen was the experimental unit for bunk displacements. Displacements were analyzed as repeated measures with the repeated variable of time. In Experiment 1, the time to eat and drink was similar across treatments (P ≥ 0.17). However, TRANS laid down in 16.5 min while DEPR did not lay down until 70.5 min post-arrival to pen (P0.01). Deprived steers had greater bunk displacements in the first 70 min post-feed access than CON or TRANS, though displacements among treatments from 100 to 120 min post-feed access were similar (treatment × time: P = 0.02). In Experiment 2, both 8H and 18H steers laid down approximately 25 min post-home pen arrival (P = 0.14). There was no effect of transit duration or duration by time on bunk displacements (P ≥ 0.20), though displacements were greater from 0 to 20 min than from 20 to 30 min post-feed access (time: P = 0.04). Steers that were deprived of feed and water were highly motivated to access those resources, while transported steers prioritized laying down. Producers should consider these priorities when preparing to receive cattle from a long transit event.Because of the segmentation of the cattle industry, cattle are transported at least once during their lives. The objective of these two studies was to determine if transportation, feed and water deprivation, and/or transit duration changed the behavior of feedlot steers. The first study found steers transported for 18 h preferred to lay down instead of competing for food, unlike steers that were deprived of food and water for 18 h. Bunk displacements were also increased in steers deprived of food and water, indicating increased aggression. In the second study examining effects of transit duration (8 vs. 18 h), steers from both treatments laid down within 25 min of arrival back to the home pens. There were no differences in the frequency of bunk displacements between treatments. Producers should consider the increased motivation for cattle to lay down after transportation and the increased aggression at the feed bunk in food-deprived cattle when developing post-arrival management strategies.

Rationale: Diffuse intrinsic pontine glioma (DIPG), a lethal brain tumor, is the leading cause of brain tumor–related death in children. Over the past few decades clinical trials have shown no improvement in outcome. The purpose of this case study is to detail and discuss the use of Antineoplastons A-10 (Atengenal) and AS2-1 (Astugenal) in the treatment of an eleven-year-old female with a newly diagnosed DIPG. Objectives: The patient described here was enrolled into BT-11, a Phase II protocol utilizing Antineoplastons A-10 and AS2-1 in the treatment of brainstem gliomas. The patient’s tumor response to therapy was measured by sequential MRIs of the brain, with and without gadolinium contrast. Findings: At her presentation to the Burzynski Clinic (BC), the patient was alert, and weighed 42.1 Kg. Physical examination showed dysfunction of the 6th and 7th cranial nerves, with lateral movement of the left eye being decreased by approximately 30% and with left-sided facial weakness being present. The patient obtained a baseline MRI, with and without gadolinium. Post-gadolinium T1-weighted axial images showed a 0.80 cm2 enhancing pontine mass and a 2.70 cm2 non-enhancing left-sided brainstem mass. Following Antineoplastons (ANP), the patient achieved a complete response (CR) of the enhancing pontine mass. At that time, physical examination, especially neurologic examination, showed no abnormalities. The patient was last seen at the BC on October 15, 2004 and she was in excellent health with no evidence of new/recurrent disease. On August 10, 2021, correspondence with the patient indicated that she continued in excellent health (>25 years survival). Conclusions: ANP is an effective treatment for DIPG and for a variety of low- and high-grade brain tumors. Multiple Phase II protocols utilizing ANP have now been completed and its impact on the treatment of brain tumors has been widely published.

In Politik, Wissenschaft und Praxis wird die Frage diskutiert, ob eine institutionelle Trennung des Angebots von Finanzdienstleistungsprodukten und der diesbezüglichen Beratung der Kunden zu einer besseren Beratungsqualität für die Nachfrager führt. Die Studie setzte sich zum Ziel, die Thesen und Zusammenhänge dieses sogenannten „Trennmodells“ theoretisch und empirisch zu überprüfen. Die Forschungsfrage lautete: Verbessert die institutionelle Trennung von Beratung zu und Angebot von Finanzdienstleistungen die Beratungsqualität für die Nachfrager von Finanzdienstleistungen? Auf Basis von theoretischen Überlegungen führte das Marktforschungsunternehmen Statista im Auftrag des DIVA im Frühjahr 2021 eine repräsentativen Onlinebefragung durch. 2000 Entscheider ab 18 Jahren aus privaten Haushalten in Deutschland, welche in den letzten 3 Jahren eine Finanz-/ Vorsorgeberatung erhalten haben, wurden nach ihren Einstellungen, Erwartungen und Erfahrungen mit Finanzberatung und den verschiedenen Akteuren im Markt der Finanzdienstleistungen befragt. Das Deutsche Institut für Vermögensbildung und Alterssicherung (DIVA) ist das Forschungsinstitut des Bundesverbands Deutscher Vermögensberater (BDV) und Hochschulinstitut der Fachhochschule der Wirtschaft (FHDW).

This study examined the effects of injectable vitamin C (VC) before transport and duration of transit on feedlot performance, inflammation, and muscle fatigue in cattle. One hundred thirty-two Angus-cross steers (393 ± 4 kg) were stratified by body weight (BW) to a 2 × 2 factorial of intramuscular injection (INJ; 20 mL/steer): VC (250 mg sodium ascorbate/mL) or saline (SAL) and road transit duration (DUR): 18 h (18-h; 1,770 km) or 8 h (8-h; 727 km). On day 0, steers were weighed and given INJ of VC or SAL immediately before transport. Upon return (day 1), BW and blood were collected before steers returned to pens equipped with GrowSafe bunks. Steers were weighed on days 0, 1, 7, 15, 30, 31, 54, and 55. Data were analyzed via ProcMixed of SAS (experimental unit = steer; 32 to 34 steers/treatment) with fixed effects of INJ, DUR, and the interaction. Blood was collected on days −5, 1, 2, 3, and 7 (n = 9 steers/treatment); blood parameters were analyzed as repeated measures with the repeated effect of day. Area under the curve (AUC) for plasma ferric reducing antioxidant power (FRAP) was calculated using R. Final BW was greater for 8 h compared to 18 h (P = 0.05) with no effect of INJ or interaction (P ≥ 0.51). Dry matter intake (DMI) from days 1 to 7 was greater for VC-8, intermediate for VC-18 and SAL-18, and least for SAL-8 (P = 0.02). Overall, DMI tended to be greatest for SAL-18, intermediate for VC-18 and VC-8, and least for SAL-8 (P = 0.08). Days 7 to 31 gain:feed (G:F) was greatest for VC-18 compared to other treatments (INJ × DUR, P = 0.05), and there was no effect of treatment on overall G:F (P ≥ 0. 19). There was no INJ or INJ × DAY (P ≥ 0.17) effect on serum lactate, haptoglobin, or non-esterified fatty acid. However, these blood parameters were greater on day 1 for 18 h compared to 8 h, and both treatments returned to near baseline by day 3 (DUR × DAY, P < 0.01). Plasma ascorbate concentrations on day 1 were greater for VC compared to SAL and returned to baseline by day 2 (INJ × DAY, P < 0.01). Plasma FRAP AUC from days −5 to 3 was greatest for VC-18, intermediate for VC-8 and SAL-8, and least for SAL-18 (INJ × DAY, P = 0.02). This suggests an antioxidant prior to long-haul transit positively influenced antioxidant capacity; however, VC did not improve overall post-transit performance. Although longer transit duration increased indicators of muscle fatigue and inflammation, post-transit performance was not appreciably different between transit durations.

We used a murine model of postsurgical osteomyelitis (OM) to evaluate the relative virulence of the Staphylococcus aureus strain LAC and five isogenic variants that differ in the functional status of saeRS and sarA relative to each other. LAC and a variant in which saeRS activity is increased (saeC) were comparably virulent to each other, while ΔsaeRS, ΔsarA, ΔsaeRS/ΔsarA, and saeC/ΔsarA mutants were all attenuated to a comparable degree. Phenotypic comparisons including a mass-based proteomics approach that allowed us to assess the number and abundance of full-length proteins suggested that mutation of saeRS attenuates virulence in our OM model owing primarily to the decreased production of S. aureus virulence factors, while mutation of sarA does so owing to protease-mediated degradation of these same virulence factors. This was confirmed by demonstrating that eliminating protease production restored virulence to a greater extent in a LAC sarA mutant than in the isogenic saeRS mutant. Irrespective of the mechanism involved, mutation of saeRS or sarA was shown to result in reduced accumulation of virulence factors of potential importance. Thus, using our proteomics approach we correlated the abundance of specific proteins with virulence in these six strains and identified 14 proteins that were present in a significantly increased amount (log2 ≥ 5.0) in both virulent strains by comparison to all four attenuated strains. We examined biofilm formation and virulence in our OM model using a LAC mutant unable to produce one of these 14 proteins, specifically staphylocoagulase. The results confirmed that mutation of coa limits biofilm formation and, to a lesser extent, virulence in our OM model, although in both cases the limitation was reduced by comparison to the isogenic sarA mutant.

In this report, we have developed a simple approach using single-detector fluorescence autocorrelation spectroscopy (FCS) to investigate the Förster resonance energy transfer (FRET) of genetically encoded, freely diffusing crTC2.1 (mTurquoise2.1–linker–mCitrine) at the single molecule level. We hypothesize that the molecular brightness of the freely diffusing donor (mTurquoise2.1) in the presence of the acceptor (mCitrine) is lower than that of the donor alone due to FRET. To test this hypothesis, the fluorescence fluctuation signal and number of molecules of freely diffusing construct were measured using FCS to calculate the molecular brightness of the donor, excited at 405 nm and detected at 475/50 nm, in the presence and absence of the acceptor. Our results indicate that the molecular brightness of cleaved crTC2.1 in a buffer is larger than that of the intact counterpart under 405-nm excitation. The energy transfer efficiency at the single molecule level is larger and more spread in values as compared with the ensemble-averaging time-resolved fluorescence measurements. In contrast, the molecular brightness of the intact crTC2.1, under 488 nm excitation of the acceptor (531/40 nm detection), is the same or slightly larger than that of the cleaved counterpart. These FCS-FRET measurements on freely diffusing donor-acceptor pairs are independent of the precise time constants associated with autocorrelation curves due to the presence of potential photophysical processes. Ultimately, when used in living cells, the proposed approach would only require a low expression level of these genetically encoded constructs, helping to limit potential interference with the cell machinery.

We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

Mutation of purR was previously shown to enhance the virulence of Staphylococcus aureus in a murine sepsis model, and this cannot be fully explained by increased expression of genes within the purine biosynthesis pathway. Rather, the increased production of specific S. aureus virulence factors, including alpha toxin and the fibronectin-binding proteins, was shown to play an important role. Mutation of purR was also shown previously to result in increased abundance of SarA. Here, we demonstrate by transposon sequencing that mutation of purR in the USA300 strain LAC increases fitness in a biofilm while mutation of sarA has the opposite effect. Therefore, we assessed the impact of sarA on reported purR-associated phenotypes by characterizing isogenic purR, sarA, and sarA/purR mutants. The results confirmed that mutation of purR results in increased abundance of alpha toxin, protein A, the fibronectin-binding proteins, and SarA, decreased production of extracellular proteases, an increased capacity to form a biofilm, and increased virulence in an osteomyelitis model. Mutation of sarA had the opposite effects on all of these phenotypes and, other than bacterial burdens in the bone, all of the phenotypes of sarA/purR mutants were comparable to those of sarA mutants. Limiting the production of extracellular proteases reversed all of the phenotypes of sarA mutants and most of those of sarA/purR mutants. We conclude that a critical component defining the virulence of a purR mutant is the enhanced production of SarA, which limits protease production to an extent that promotes the accumulation of critical S. aureus virulence factors.