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Background A rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies. Objective To evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus  galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies. Methods In this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n = 6), probable (n = 22), possible IA (n = 55), or no IA (n = 88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman’s correlation analysis and kappa statistics were performed to determine the agreement between the tests. Results GM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores ( p  = 0.01). The observed agreement between the tests at 0.5 ODI was almost perfect ( p  < 0.001). After excluding patients who received mold-active antifungal prophylaxis or treatment, the SEN, SPE, NPV, and diagnostic accuracy for proven/probable IA were 76.2%, 100%, 93.3%, and 94.5%, respectively. Conclusions Serum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.

•With the SARS-CoV-2 pandemic, the need for development of effective, safe and widely available vaccine options has emerged.•Considering the findings from the ongoing research, including the interim results from the phase-1 and 2 studies presented in this article, ERUCoV-VAC, the development process of which started in 2020, has been approved for emergency use in December 2021 in Türkiye.•It is included in COVID-19 vaccine programme as a new option for both vaccine-naive and previously vaccinated individuals as a first or booster-shot. Development of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine. Double-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronegative healthy adults aged 18–55 years (18–64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 μg or 6 μg unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 μg or 6 μg (an inactivated vaccine containing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer-generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391). Forty-four participants (3 μg [n:17], 6 μg [n:17], placebo [n:10]) in phase 1 and 250 (3 μg [n:100], 6 μg [n:100], placebo [n:50]) in phase 2 received ≥1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most common AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 μg and 6 μg groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4–10.3) vs. 8.6 (7.0–10.2) at day 43 (p = 0.7357) and 9.7 (6.0–13.4) vs. 10.8 (8.8–12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3–10.5) vs. 9.0 (7.2–10.8) at day 43 (p = 0.5393) and 11.0 (7.0–14.9) vs. 12.3 (10.3–14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5–98.3) vs 94.1 % (71.3–99.8) at day 43 (p = 0.8727) and 92.8 % (66.1–99.8) vs. 100 % (79.4–100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 μg and 6 μg groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 μg and 6 μg groups were comparable neutralising antibody (MNT50): GMTs (95 %CI) were 30.0 (37.9–22.0) vs. 34.9 (47.6–22.1) at day 43 (p = 0.0666) and 34.2 (23.8–44.5) and 39.6 (22.7–58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0–37.7) and 30.1 (18.5–41.6) at day 43 (p = 0.3366) and 34.2 (23.8–44.5) and 39.6 (22.7–58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 %CI) were 95.7 % (91.4–99.8) vs. 98.9 % (96.9–100.0) at day 43 (p = 0.8710) and 96.6 % (92.8–100.0) vs 98.9 % (96.7–100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 μg and 6 μg groups, respectively. Two-dose regimens of ERUCoV-VAC 3 μg and 6 μg 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination. Data availability Data will be made available on request.

Acute ischemic stroke (AIS) is a devastating complication of COVID-19 with high morbidity and mortality. In this study, we reported the frequency, characteristics, and outcome of AIS in patients with COVID-19. This multicenter and cross-sectional study was conducted between April 2020 and February 2021. Among the hospitalized patients with COVID-19, the detailed characteristics of those with and without AIS were recorded and compared. Six hundred ninety-three patients were included in the study. Acute ischemic stroke was detected in 16 (2.31%) patients, the median age was 77 (range, 48-91) years, and 10 (62.5%) were female. The median NIHSS score at admission was 9 (range, 3-17). Total anterior circulation infarction (TACI) was the most common (37.5%) type and cardioembolism was the most common etiology (37.5%). Nine patients (56.25%) developed AIS within 24 hours of having COVID-19. COVID-19 severity was severe or critical in seven patients (43.75%). Eight patients died, and eight were discharged. Patients with AIS had a higher rate of hypertension, coronary artery disease, heart failure, a history of myocardial infarction, a history of cerebrovascular disease, severe and critical COVID-19, a higher mean age, and a longer ICU stay compared with those without AIS (p<0.001 for each). AIS can occur in patients with COVID-19 and is associated with mortality. Acute ischemic stroke is encountered at any stage of COVID-19, especially within the first 72 hours of the diagnosis, in older patients with comorbidities and severe COVID-19. There is an increased risk of AIS in patients with COVID-19 with a history of stroke.

The environment, which is the habitat of all living things and contains the natural resources necessary to sustain life, is an issue of vital importance for humanity. This study was conducted to examine the conceptual structures that form the concept of “environment” in the minds of 8th grade students and to reveal their cognitive understanding and perceptions. The study was conducted in a district located in eastern Türkiye. Although students have a solid understanding of ecological concepts, especially those related to biotic elements, there is a clear need to deepen their awareness of the interconnectedness of environmental components, including abiotic factors and human impacts. According to the results obtained from the study, although students have a certain level of conceptual structure, this is not considered sufficient. In addition, the fact that students associate the concept of environment with a narrow group of words suggests that their conceptual structures may be underdeveloped. There may be some limitations in this study due to the scope of the study and the sample group. The subject of studying with a larger sample group and different techniques can be investigated. Using active learning strategies can deepen students’ understanding and emotional connection to the environment.

Coronavirus disease 2019 (Covid-19) has many different ocular manifestations. This study evaluates the effects of the disease and the steroid used in this disease on ocular structures.  To evaluate the effects of Covid-19 and the steroids used in the treatment of severe infection on ocular structures and choroidal thickness. This prospective study included 76 eyes of 76 patients who were hospitalized due to Covid-19 and 30 eyes of 30 healthy volunteering controls. Group I included 35 eyes who were hospitalized due to moderate-to-severe involvement that received steroid treatment, group II included 41 eyes with moderate involvement that did not require steroid treatment, and group III included 30 eyes with age- and gender-matched control subjects. Ophthalmological examination and imaging results of the patients obtained in the third week and third month after the diagnosis were compared between the groups. Mean age of all participants was 40.2 ± 6.1 years. In the third week after the diagnosis of Covid-19, choroidal thickness in all regions (subfoveal, nasal, and temporal) was significantly greater in group I than in group II (for all,  <0.001). Moreover, choroidal thicknesses were significantly higher in group I and group II than in the control group (for all,  <0.001). In the third month, all the groups had similar choroidal thickness values (for subfoveal, nasal, and temporal; =0.058,  =0.111,  =0.079, respectively). Our findings showed that Covid-19 infection causes choroidal thickening by affecting the choroidal layer and that steroid treatment further increases this thickness in the acute period. In addition, the reversal of this thickening to the normal level within a period of three months indicates that the effect of the disease on the choroid is reversible.

NOABSTRACTBreast cancer remains one of the most prevalent malignancies among women worldwide, underscoring the need for physiologically relevant in vitro models that closely mimic the tumor microenvironment. While two-dimensional (2D) cultures are commonly used, they fall short in replicating in vivo conditions. This study aimed to develop a three-dimensional (3D) breast cancer model using various biomaterial-based scaffolds to evaluate their effects on cell viability, morphology, and adhesion.MCF-7 breast cancer cells were cultured on five different 3D printed scaffolds composed of PLA, PCL, PET, HIPS, and TPU. Scaffold designs were created using SolidWorks and Slic3r, followed by 3D printing. Cell viability was assessed using the crystal violet assay, and morphological analysis was conducted through scanning electron microscopy (SEM) and confocal microscopy. Statistical analysis was performed using one-way ANOVA.Among all tested scaffolds, TPU scaffolds exhibited superior performance, significantly enhancing MCF-7 cell viability compared to HIPS, PCL, and PET (***p ≤ 0.001), and slightly outperforming PLA (ns, p > 0.05). SEM analysis revealed enhanced cell spreading and surface attachment on TPU, while HIPS showed minimal interaction. Confocal imaging further confirmed superior nuclear localization and mitochondrial activity on TPU scaffolds, indicating improved metabolic activity and 3D cellular organization.The findings confirm that TPU scaffolds provide the most supportive microenvironment for MCF-7 cells in 3D culture, offering superior viability, morphology, and cellular interaction. PLA also showed promising results but was slightly less effective than TPU. In contrast, HIPS was the least effective and appears unsuitable as a standalone scaffold material. These results support the use of TPU for physiologically relevant 3D in vitro models of breast cancer for future research and therapeutic applications.

Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/β-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/β-catenin pathway antagonists—secreted frizzled-related protein 1 and Wnt inhibitory factor 1—on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia. Response to tyrosine kinase inhibitors was analyzed in secreted frizzled-related protein 1 and Wnt inhibitory factor 1 stably transfected K562 cells. Experiments were repeated using a tetracycline-inducible expression system, confirming previous results. In addition, response to tyrosine kinase inhibitor treatment was also analyzed using the secreted frizzled-related protein 1 expressing, BCR-ABL positive MEG01 cell line, in the presence and absence of a secreted frizzled-related protein 1 inhibitor. Our data suggests that total cellular β-catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total β-catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. We suggest that Wnt antagonists carry the potential to be exploited in designing new agents and strategies for the advanced and resistant forms of chronic myeloid leukemia.

Prosthetic joint infections (PJIs) can lead to extended hospital stays, necessitate additional surgeries, and require antimicrobial treatment, thereby increasing costs and causing significant morbidity. This study aims to ascertain surgeon-specific infection rates and identify risk factors associated with PJIs. This research was conducted with two study arms between January 1, 2017, and February 28, 2019. In the first arm, all cases undergoing primary total knee and hip arthroplasty by the same surgeon were prospectively included and monitored for the development of PJIs. In the second arm, all patients admitted to the same surgeon due to PJI were included. The first arm comprised 152 patients, of whom five developed PJIs (3.2%). Risk factors for PJI development included diabetes mellitus (p=0.030), rheumatoid arthritis (p=0.014), superficial surgical wound infections in the same joint (p=0.001), and postoperative hematomas (p=0.008). In the second arm, 23 patients with PJIs were included. Gram-positive microorganisms (84.6%) were the most frequently isolated pathogens. The overall treatment success rate stood at 76%, with a treatment success rate of 72.2% for patients receiving daptomycin. Effective measures such as perioperative glycemic control, regulation of immunosuppressive drugs, management of anticoagulant therapy, postoperative wound care by trained personnel, adherence to infection control protocols, and tailoring of PJI treatments based on local surveillance data are crucial for preventing PJIs and achieving treatment success.

ObjectiveVaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols.SettingInoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose.MethodsWe collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status.ResultsWe identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac.ConclusionEffective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination.

The incidence of hospital-acquired infections increases due to the rising use of invasive procedures and increased length of hospital stay. The incidence of colonization and infection with multidrug-resistant microorganisms also increased along with the use of broad-spectrum antibiotics. Besides, due to limited antibiotic treatment options, infection control measures are of great importance. Using prevention bundles including three or five infection control measures according to the characteristics of the units rather than single measures is more effective. The most frequently applied infection control bundles aim at preventing ventilator-associated pneumonia, central line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site infections, and spread of resistant Gram-negative microorganisms. It is critically important that the bundle parameters are applied and controlled for 24 hours and seven days. The basic principles of all bundles include avoiding use of unnecessary invasive applications, compliance with the rules of aseptic and antiseptic procedures during the daily medical practice, discontinuation of invasive devices as soon as they are no longer required and compliance with hand hygiene. Implementation of evidence-based infection control bundles, provides an important opportunity for the delivery of safe and regular healthcare services. After the bundle applications, the task of the infection control committee is to carry out surveillance programs for compliance with the bundle parameters and to determine the rate of infections, and give feedback. By means of the feedback, compliance with the bundles and decreased infection rates are observed. In this paper, we present a review of the literature on the bundle parameters implemented in units and changes in hospital-acquired infections via compliance with these parameters.