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The primary aim of this study was to analyse the influence of honeybee venom on various aspects of Drosophila melanogaster physiology and to assess the efficacy of adipokinetic hormone (AKH) in mitigating venom toxicity. We examined the harmful effects of venom on the thoracic muscles and central nervous system of Drosophila, as well as the potential use of AKH to counteract these effects. The results demonstrated that envenomation altered AKH levels in the Drosophila CNS, promoted cell metabolism, as evidenced by an increase in citrate synthase activity in muscles, and improved relative cell viability in both organs incubated in vitro. Furthermore, venom treatment reduced the activity of two key antioxidative stress enzymes, superoxide dismutase and catalase, and modified the expression of six genes encoding immune system components ( Keap1 , Relish , Nox , Eiger , Gadd45 , and Domeless ) in both organs. The venom also disrupted muscle cell ultrastructure, specifically myofibrils, and increased the release of arginine kinase into the incubation medium. Notably, when administered alongside the venom, AKH influenced the majority of these changes. AKH was the most effective in minimising damage to the ultrastructure of muscle cells and preventing the release of arginine kinase from muscles to the medium; however, in other parameters, the effect was modest or minimal. Given that honeybee venom often affects humans, understanding its actions and potential ways to reduce or eliminate them is valuable and could lead to the development of pharmacologically important compounds that may have clinical relevance.

We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1–3 cycles.

Human toxocariasis is a helminthozoonosis caused by the migration of Toxocara species larvae through an organism. The infection in humans is transmitted either by direct ingestion of the eggs of the parasite, or by consuming undercooked meat infested with Toxocara larvae. This parasitosis can be found worldwide, but there are significant differences in seroprevalence in different areas, depending mainly on hot climate conditions and on low social status. However, the literature estimates of seroprevalence are inconsistent. Infected patients commonly present a range of symptoms, e.g., abdominal pain, decreased appetite, restlessness, fever, and coughing. This manuscript presents a case report of a polytraumatic patient who underwent a two-phase spinal procedure for a thoracolumbar fracture. After the second procedure, which was a vertebral body replacement via thoracotomy, the patient developed a pathologic pleural effusion. A microscopic cytology examination of this effusion revealed the presence of Toxocara species larvae. Although the patient presented no specific clinical symptoms, and the serological exams (Enzyme–linked immunosorbent assay (ELISA), Western blot) were negative, the microscopic evaluation enabled a timely diagnosis. The patient was successfully treated with albendazole, with no permanent sequelae of the infection.

The aim of this study was to investigate the predictors of long-term clinical outcome of heart failure (HF) patients who survived first year after initiation of cardiac resynchronization therapy (CRT). This was a single-center observational cohort study of CRT patients implanted because of symptomatic HF with reduced ejection fraction between 2005 and 2013. Left ventricle (LV) diameters and ejection fraction, New York Heart Association (NYHA) class, and level of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) were assessed at baseline and 12 months after CRT implantation. Their predictive power for long-term HF hospitalization and mortality, and cardiac and all-cause mortality was investigated. A total of 315 patients with left bundle branch block or intraventricular conduction delay who survived >1 year after CRT implantation were analyzed in the current study. During a follow-up period of 4.8±2.1 years from CRT implantation, 35.2% patients died from cardiac (19.3%) or non-cardiac (15.9%) causes. Post-CRT LV ejection fraction and LV end-systolic diameter (either 12-month value or the change from baseline) were equally predictive for clinical events. For NT-proBNP, however, the 12-month level was a stronger predictor than the change from baseline. Both reverse LV remodeling and 12-month level of NT-proBNP were independent and comparable predictors of CRT-related clinical outcome, while NT-proBNP response had the strongest association with all-cause mortality. When post-CRT relative change of LV end-systolic diameter and 12-month level of NT-proBNP (dichotomized at -12.3% and 1230 ng/L, respectively) were combined, subgroups of very-high and very-low risk patients were identified. The level of NT-proBNP and reverse LV remodeling at one year after CRT are independent and complementary predictors of future clinical events. Their combination may help to improve the risk stratification of CRT patients.

Abundances of EPT larvae sampled in a Central European locality affected by mining and smelting, as well as by the continual inflow of treated communal wastewaters (WWs), were recorded. High concentrations of trace metals in water (maximum 1200 µg·L–1 for zinc) and sediments (maximum 140,000 mg·kg–1 in dry weight for lead) were found at the most contaminated sites. The highest loads of pesticides, pharmaceuticals, and illegal drugs were found under the WW effluent. Other associated factors such as the physicochemical parameters of the water and alterations to microhabitats were also evaluated and taken into account. Although EPT richness was lower at affected sites, abundances did not fall. Stoneflies were dominant at unaffected sites, while caddisflies dominated at affected sites. Only baetid mayflies were detected at the sites contaminated by trace metals and WWs; ephemerellid, heptageniid, and leptophlebiid mayflies were absent from these sites. The site contaminated by trace metals was also inhabited by numerous limnephilid caddisflies, in which limb malformations were detected in up to 11.8% of all specimens of a single taxon. Downstream from the entrance of the WWs, the locality was dominated by hydropsychid caddisflies. The increasing prevalence of predator or passive filter-feeding strategies in these EPT communities was significantly related to increasing water conductivity and acute ecosystemic exposure to ‘poorly treated’ WWs.

Nanostructured titanium has become a useful material for biomedical applications such as dental implants. Certain surface properties (grain size, roughness, wettability) are highly expected to promote cell adhesion and osseointegration. The aim of this study was to compare the biocompatibilities of several titanium materials using human osteoblast cell line hFOB 1.19. Eight different types of specimens were examined: machined commercially pure grade 2 (cpTi2) and 4 (cpTi4) titanium, nanostructured titanium of the same grades (nTi2, nTi4), and corresponding specimens with laser-treated surfaces (cpTi2L, cpTi4L, nTi2L, nTi4L). Their surface topography was evaluated by means of scanning electron microscopy. Surface roughness was measured using a mechanical contact profilometer. Specimens with laser-treated surfaces had significantly higher surface roughness. Wettability was measured by the drop contact angle method. Nanostructured samples had significantly higher wettability. Cell proliferation after 48 hours from plating was assessed by viability and proliferation assay. The highest proliferation of osteoblasts was found in nTi4 specimens. The analysis of cell proliferation revealed a difference between machined and laser-treated specimens. The mean proliferation was lower on the laser-treated titanium materials. Although plain laser treatment increases surface roughness and wettability, it does not seem to lead to improved biocompatibility.

Bees originally developed their stinging apparatus and venom against members of their own species from other hives or against predatory insects. Nevertheless, the biological and biochemical response of arthropods to bee venom is not well studied. Thus, in this study, the physiological responses of a model insect species (American cockroach, Periplaneta americana) to honeybee venom were investigated. Bee venom toxins elicited severe stress (LD50 = 1.063 uL venom) resulting in a significant increase in adipokinetic hormones (AKHs) in the cockroach central nervous system and haemolymph. Venom treatment induced a large destruction of muscle cell ultrastructure, especially myofibrils and sarcomeres. Interestingly, co-application of venom with cockroach Peram-CAH-II AKH eliminated this effect. Envenomation modulated the levels of carbohydrates, lipids, and proteins in the haemolymph and the activity of digestive amylases, lipases, and proteases in the midgut. Bee venom significantly reduced vitellogenin levels in females. Dopamine and glutathione (GSH and GSSG) insignificantly increased after venom treatment. However, dopamine levels significantly increased after Peram-CAH-II application and after co-application with bee venom, while GSH and GSSG levels immediately increased after co-application. The results suggest a general reaction of the cockroach body to bee venom and at least a partial involvement of AKHs.

Globally, instrumentally based assessments of tsunamigenic potential of subduction zones have underestimated the magnitude and frequency of great events because of their short time record. Historical and sediment records of large earthquakes and tsunamis have expanded the temporal data and estimated size of these events. Instrumental records suggests that the Mexican Subduction earthquakes produce relatively small tsunamis, however historical records and now geologic evidence suggest that great earthquakes and tsunamis have whipped the Pacific coast of Mexico in the past. The sediment marks of centuries old-tsunamis validate historical records and indicate that large tsunamigenic earthquakes have shaken the Guerrero-Oaxaca region in southern Mexico and had an impact on a bigger stretch of the coast than previously suspected. We present the first geologic evidence of great tsunamis near the trench of a subduction zone previously underestimated as potential source for great earthquakes and tsunamis. Two sandy tsunami deposits extend over 1.5 km inland of the coast. The youngest tsunami deposit is associated with the 1787 great earthquake, M 8.6, producing a giant tsunami that poured over the coast flooding 500 km alongshore the Mexican Pacific coast and up to 6 km inland. The oldest event from a less historically documented event occurred in 1537. The 1787 earthquake, and tsunami and a probable predecessor in 1537, suggest a plausible recurrence interval of 250 years. We prove that the common believe that great tsunamis do not occur on the Mexican Pacific coast cannot be sustained.

Accretionary wedges of orogenic belts develop differently based on the direction of thrusting, which can be perpendicular to oblique to the belt. In the case of oblique thrusting, stress partitioning occurs, which dissects the accretionary wedge, changes the tectonic regime from thrusting to strike-slip, and causes the external parts to rotate laterally. The relationship between stress partitioning and external rotation is not yet fully understood and has typically been studied separately. This study investigates the Falkenstein-Mikulov fault zone in the Outer Western Carpathians (OWC) wedge as an illustrative example of the relationship between partitioning and rotation. Using a prominent limestone marker horizon and a multidisciplinary approach-including geomorphological analysis, geological mapping, paleostress analysis, and shallow and deep-seismic geophysical surveys-we defined the fault zone's unique arcuate geometry and identified several stages of tectonic activity. Paleostress inversion reveals multiple tectonic phases highlighting a transition from thrusting to strike-slip faulting. After thrusting (Phase D1), transversal strike-slip faults segmented the wedge coinciding with significant counterclockwise rotational patterns (Phase D2). Finally, during Phase D3, an arcuate strike-slip fault zone parallel to thrusting direction evolved, also revealing rotation of 12° over a distance of 10 km. These phases interplayed in the accretionary wedge at the same time, and their apparent succession is the result of shifting of the tectonic activity during the progressive development of the wedge. Thus, the thrusting activity in the front of the wedge was followed by rotational motion along the lateral ramps and finalized by parallel strike-slip faulting. This model explains how accretionary wedges undergo external rotation due to curved strike-slip faulting in the final stages of thrusting and has significant implications for understanding the broader tectonic evolution of accretionary wedges worldwide.

ObjectiveTo evaluate the safety and efficacy of CD19 chimeric antigen receptor (CAR) T cell therapy in a patient with refractory lupus nephritis who experienced severe disease flare during immunosuppressive washout, and to assess whether pulse corticosteroid intervention affects CAR T cell therapeutic outcomes.MethodsWe report a single case of a 22-year-old woman with SLE and lupus podocytopathy refractory to multiple therapies including rituximab, belimumab and obinutuzumab. The patient was treated under single-patient IND (#30146) with autologous CD19 CAR T cells (KYV-101). During the preinfusion washout period, she developed severe lupus flare requiring pulse intravenous methylprednisolone. Clinical outcomes, CAR T cell expansion, B cell depletion and laboratory parameters were monitored before and after therapy.ResultsDespite experiencing severe lupus flare (fever, rash, arthritis, anti-dsDNA elevation, hypocomplementaemia) during washout, pulse methylprednisolone (250 mg intravenous, rapidly tapered) successfully controlled symptoms without compromising subsequent CAR T cell expansion (peak 15.5 cells/µL on day 7). The patient achieved sustained clinical remission with SLE Disease Activity Index Score decreasing from 17 prior to leukapheresis to 4 by week 17. At 12 months postinfusion, she remained in drug-free remission with stable kidney function and had returned to full-time work.ConclusionThis case report illustrates that targeted pulse corticosteroids during CAR T cell therapy washout can effectively manage severe lupus flares without impairing therapeutic efficacy.