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An epidemic of foodborne infection with Escherichia coli associated with a high rate of the hemolytic–uremic syndrome and caused by a novel E. coli strain (O104:H4) recently occurred in Germany. This final report updates epidemiologic, clinical, and microbiologic information. On May 19, 2011, the Robert Koch Institute, Germany's national-level public health authority, was informed about a cluster of three cases of the hemolytic–uremic syndrome in children admitted on the same day to the university hospital in the city of Hamburg. On May 20, a team from the Robert Koch Institute arrived in Hamburg to assist with the public health investigation. It quickly became clear that the case numbers were continuing to rise, that there were also cases in adults, and that other areas of Germany, especially northern Germany, were also affected. An investigation of the outbreak involving all levels . . .

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. Methods On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. Results Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. Conclusions The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD. Graphical Abstract

Background During weeks 32–33, 2013, 24 cases of cryptosporidiosis were notified in the city of Halle (annual mean 2008–2012: 9 cases). We investigated the outbreak to identify the source and recommend control measures, considering that between weeks 23–25 the river Saale which flows through the city centre overflowed the floodplain, parts of the city centre and damaged sewage systems. Methods We defined a case as a resident of Halle with gastroenteritis, Cryptosporidium -positive stool and disease onset weeks 27 through 47. In a case–control study among kindergarten children, we compared cases and controls regarding environmental exposure, use of swimming pools, zoo visits and tap water consumption 14 days pre-onset or a corresponding 14-days-period (controls) and adjusted for residence. Stool specimens were tested by microscopy and PCR, and Cryptosporidium DNA was sequenced. Samples from public water system, swimming pools and river Saale were examined for Cryptosporidium oocysts (microscopy and PCR). Results Overall, 167 cases were detected, 40/167 (24%) were classified as secondary cases. First disease onsets occurred during week 29, numbers peaked in week 34 and started to decrease in week 36. Median age was 8 years (range: 0–77). Compared to controls (n = 61), cases (n = 20) were more likely to report visits to previously flooded areas (OR: 4.9; 95%-CI: 1.4-18) and the zoo (OR: 2.6; 95%-CI: 0.9-7.6). In multivariable analysis visits to the floodplain remained the sole risk factor (OR: 5.5; 95%-CI: 1.4-22). Only C.hominis of a single genotype (IbA9G2) was detected in stools. Oocysts were detected in samples from the river, two local lakes and three public swimming pools by microscopy, but not in the public water supply. Conclusions Evidence suggests that activities in the dried out floodplain led to infection among children. Secondary transmissions may be involved. Consequently, authorities recommended to avoid playing, swimming and having picnics in the flood-affected area. Health authorities should consider the potential health risks of long-term surviving parasites persisting on flooded grounds and in open waters even several weeks after the flooding and of bathing places close to sewage spill-overs. Preventive measures comprise water sampling (involving parasites), information of the public and prolonged closures of potentially contaminated sites.

Background Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. Methods Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. Results The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. Discussion The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.

There is an increase of pathogenic multidrug-resistant bacteria globally due to the misuse of antibiotics. Recently, more scientists used metal nanoparticles to counteract antibacterial resistance. In this study, orange peel waste (OPW) was used for selenium nanoparticles’ (Se-NPs) biosynthesis through the green and ecofriendly method, and their applications as antibacterial and antibiofilm agents. Green biosynthesized Se-NPs were characterized using FTIR, XRD, SEM, EDAX, and TEM. Characterization results revealed that biosynthesized Se-NPs were highly crystalline, spherical, and polydisperse, and had sizes in the range of 16–95 nm. The biosynthesized Se-NPs were evaluated as antibacterial and antibiofilm activities against multidrug-resistant bacteria. Results illustrated that Se-NPs exhibited potential antibacterial activity against Gram-positive bacteria (S. aureus ATCC 29213 and biofilm-producing clinical isolates of S. aureus) and Gram-negative bacteria (Pseudomonas aeruginosa PAO1, MDR, biofilm, and quorum-sensing and producing clinical isolates of MDR P. aeruginosa, MDR E. coli, and K. pneumonia). Moreover, results illustrated that S. aureus ATCC 29213 was the most sensitive bacteria to Se-NPs at 1000 µg/mL, where the inhibition zone was 35 mm and MIC was 25 µg/mL. Furthermore, Se-NPs at 0.25 and 0.5 MIC decreased the biofilm significantly. The largest inhibition of biofilm was noticed in MDR K. pneumonia, which was 62% and 92% at 0.25 and 0.5 MIC, respectively. In conclusion, Se-NPs were successfully biosynthesized using OPW through the green method and had promising antibacterial and antibiofilm activity against multidrug-resistant bacteria, which can be used later in fighting resistant bacteria.

Rhizoctonia root-rot disease causes severe economic losses in a wide range of crops, including Vicia faba worldwide. Currently, biosynthesized nanoparticles have become super-growth promoters as well as antifungal agents. In this study, biosynthesized selenium nanoparticles (Se-NPs) have been examined as growth promoters as well as antifungal agents against Rhizoctonia solani RCMB 031001 in vitro and in vivo. Se-NPs were synthesized biologically by Bacillus megaterium ATCC 55000 and characterized by using UV-Vis spectroscopy, XRD, dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging. TEM and DLS images showed that Se-NPs are mono-dispersed spheres with a mean diameter of 41.2 nm. Se-NPs improved healthy Vicia faba cv. Giza 716 seed germination, morphological, metabolic indicators, and yield. Furthermore, Se-NPs exhibited influential antifungal activity against R. solani in vitro as well as in vivo. Results revealed that minimum inhibition and minimum fungicidal concentrations of Se-NPs were 0.0625 and 1 mM, respectively. Moreover, Se-NPs were able to decrease the pre-and post-emergence of R. solani damping-off and minimize the severity of root rot disease. The most effective treatment method is found when soaking and spraying were used with each other followed by spraying and then soaking individually. Likewise, Se-NPs improve morphological and metabolic indicators and yield significantly compared with infected control. In conclusion, biosynthesized Se-NPs by B. megaterium ATCC 55000 are a promising and effective agent against R. solani damping-off and root rot diseases in Vicia faba as well as plant growth inducer.

Introduction Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo- and radio-sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radio-sensitizer efficacy of amygdalin -folic acid nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells. Materials and methods The effects of Amy-F on MCF-7 and MDA-MB-231 cell proliferation and IC50 were assessed using MTT assay. The expression of proteins involved in several mechanisms induced by Amy-F in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immuno-modulators, and radio-sensitizing activities were evaluated via flow cytometry and ELISA assay. Results Nanoparticles demonstrated sustained Amy-F release properties and apparent selectivity towards BC cells. Cell-based assays revealed that Amy-F markedly suppresses cancer cell growth and improves radiotherapy (RT) through inducing cell cycle arrest (G1 and sub-G1), and increases apoptosis as well as reduces the proliferation of BC by down-regulating mitogen-activated protein kinases (MAPK/P38), iron level (Fe), nitric oxide (NO), and up-regulating the reactive oxygen species level (ROS). Amy-F has also been shown to suppress the expression of the cluster of differentiation (CD4 and CD80), and interfere with the Transforming growth factor beta (TGF- β)/Interferon-gamma (INF-g)/Interleukin-2 (IL-2)/Interleukin-6 (IL-6)/Vascular endothelial growth factor (VEGF) induced suppression in its signaling hub, while up-regulating natural killer group 2D receptor (NKG2D) and CD8 expression. Conclusions Collectively, the novel Amy-F either alone or in combination with RT abrogated BC proliferation.

This paper proposes a Cournot game organized by three competing firms adopting bounded rationality. According to the marginal profit in the past time step, each firm tries to update its production using local knowledge. In this game, a firm’s preference is represented by a utility function that is derived from a constant elasticity of substitution (CES) production function. The game is modeled by a 3-dimensional discrete dynamical system. The equilibria of the system are numerically studied to detect their complex characteristics due to difficulty to get an explicit form for those equilibria. For the proposed utility function, some cases with different value parameters are considered. Numerical simulations are used to provide an experimental evidence for the complex behavior of the evolution of the system. The obtained results show that the system loses its stability due to different types of bifurcations.

Zinc coumarate and zinc caffeinate nanoparticles (ZnCoNPs, ZnCaNPs) affect different biological processes. This study aimed to evaluate the mitigating action of ZnCoNPs in combination with ZnCaNPs against liver damage induced by gamma rays (γ-rays). Rats were exposed to 7 Gy of γ-rays and then injected intraperitoneally (i.p) with ZnCoNPs [2U/rat/day (5 mg/kg)] and ZnCaNPs [2U/rat/day (15 mg/kg)] for 7 consecutive days. The results showed that irradiated rats treated with ZnCoNPs (5 mg/kg/body weight) in combination with ZnCaNPs (15 mg/kg/body weight) for 7 days had a significant increases in body weight, antioxidant levels, T helper cell 4 (cluster of differentiation 4 (CD4)), and T cytotoxic cell 8 (cluster of differentiation 8 (CD8)), associated with a marked decrease in lipid peroxidation (LP), nitric oxide(NOx), total free radicals concentrate (TFRC ) , and DNA fragmentation. There were positive alterations in the morphological state, hematological parameters and the cell cycle phases. Additionally, the histopathological study demonstrated an improvement in the liver tissue of irradiated rats after treatment. Thus, ZnCoNPs and ZnCaNPs could be used as natural mitigating agents to reduce the hazards of ionizing radiation.

We studied the characteristics and survival of patients with sorafenib-treated HCC and impact of underlying etiology on outcomes. This retrospective multicenter study recruited patients with sorafenib-treated advanced HCC (12/2016 to 4/2023) till death or the study end (2/2024). Time to progression (TTP) and overall survival (OS) were recorded. We evaluated; Clinico-laboratory and imaging predictors of OS, The impact of underlying etiology on tumor variables, outcomes and tolerance for sorafenib > 6 months. This study included 706 patients. Median duration of Sorafenib therapy was 240.00 (90.00–360.00) days. Median OS was 314.00(146.00–601.00) days. Median TTP was 180.00(90.00–330.00) days. COX regression revealed that the independent factors of mortality were baseline AST, Tumor size, hepatic vein thrombosis (HVT), development of jaundice and shifting to Regorafenib. Advanced HCCs were more common on top of non-cirrhotic non-viral and HBV-related liver disease. Adverse events, TTP and tumor response didn’t differ with the underlying etiology. Median OS was lower in non-viral-related HCC than HCV-related HCC (218.00 versus 326.50 days, P -value = 0.048). Patients who continued sorafenib > 6 months had lower AFP, HVT, adverse effects and better tumor response after 3 months. OS is lower in non-viral Sorafenib-treated HCC compared with viral-related HCC and Sorafenib was well-tolerated among different HCC etiologies.