Corticosteroid therapy in regressive autism: a retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior

Background: Up to a third of children with Autism Spectrum Disorder (ASD) manifest regressive autism (R-ASD).They show normal early development followed by loss of language and social skills. Absent evidence-based therapies, anecdotal evidence suggests improvement following use of corticosteroids. This study examined the effects of corticosteroids for R-ASD children upon the 4 Hz frequency modulated evoked response (FMAER) arising from language cortex of the superior temporal gyrus (STG) and upon EEG background activity, language, and behavior. An untreated clinical convenience sample of ASD children served as control sample. Methods: Twenty steroid-treated R-ASD (STAR) and 24 not-treated ASD patients (NSA), aged 3 - 5 years, were retrospectively identified from a large database. All study participants had two sequential FMAER and EEG studies;Landau-Kleffner syndrome diagnosis was excluded. All subjects’ records contained clinical receptive and expressive language ratings based upon a priori developed metrics. The STAR group additionally was scored behaviorally regarding symptom severity as based on the Diagnostic and Statistical Manual IV (DSM-IV) ASD criteria list. EEGs were visually scored for abnormalities. FMAER responses were assessed quantitatively by spectral analysis. Treated and untreated group means and standard deviations for the FMAER, EEG, language, and behavior, were compared by paired t-test and Fisher’s exact tests. Results: The STAR group showed a significant increase in the 4 Hz FMAER spectral response and a significant reduction in response distortion compared to the NSA group. Star group subjects’ language ratings were significantly improved and more STAR than NSA group subjects showed significant language improvement. Most STAR group children showed significant behavioral improvement after treatment. STAR group language and behavior improvement was retained one year after treatment. Groups did not differ in terms of minor EEG abnormalities. Steroid treatment produced no lasting morbidity. Conclusions: Steroid treatment was associated with a significantly increased FMAER response magnitude, reduction of FMAER response distortion, and improvement in language and behavior scores. This was not observed in the non-treated group. These pilot findings warrant a prospective randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG, and standardized ASD, language and behavior measures, and a longer follow-up period. Please see related article http://www.biomedcentral.com/1741-7015/12/7

The school bus routing problem: An analysis and algorithm

In this paper we analyse a flexible real world-based model for designing school bus transit systems and note a number of parallels between this and other well-known combinatorial optimisation problems including the vehicle routing problem, the set covering problem, and one-dimensional bin packing. We then describe an iterated local search algorithm for this problem and demonstrate the sort of solutions that we can expect with different types of problem instance

Transmittivity of a Bose-Einstein condensate on a lattice: interference from period doubling and the effect of disorder

We evaluate the particle current flowing in steady state through a Bose-Einstein condensate subject to a constant force in a quasi-onedimensional lattice and to attractive interactions from fermionic atoms that are localized in various configurations inside the lattice wells. The system is treated within a Bose-Hubbard tight binding model by an out-of-equilibrium Green's function approach. A new band gap opens up when the lattice period is doubled by locating the fermions in alternate wells and yields an interference pattern in the transmittivity on varying the intensity of the driving force. The positions of the transmittivity minima are determined by matching the period of Bloch oscillations and the time for tunnelling across the band gap. Massive disorder in the distribution of the fermions will wash out the interference pattern, but the same period doubling of the lattice can be experimentally realized in a four-beam set-up. We report illustrative numerical results for a mixture of 87Rb and 40K atoms in an optical lattice created by laser beams with a wavelength of 763 nm.Comment: 13 pages, 5 figure

A hyper-heuristic with two guidance indicators for bi-objective mixed-shift vehicle routing problem with time windows

In this paper, a Mixed-Shift Vehicle Routing Problem is proposed based on a real-life container transportation problem. In a long planning horizon of multiple shifts, transport tasks are completed satisfying the time constraints. Due to the different travel distances and time of tasks, there are two types of shifts (long shift and short shift) in this problem. The unit driver cost for long shifts is higher than that of short shifts. A mathematical model of this Mixed-Shift Vehicle Routing Problem with Time Windows (MS-VRPTW) is established in this paper, with two objectives of minimizing the total driver payment and the total travel distance. Due to the large scale and nonlinear constraints, the exact search showed is not suitable to MS-VRPTW. An initial solution construction heuristic (EBIH) and a selective perturbation Hyper-Heuristic (GIHH) are thus developed. In GIHH, five heuristics with different extents of perturbation at the low level are adaptively selected by a high level selection scheme with the Hill Climbing acceptance criterion. Two guidance indicators are devised at the high level to adaptively adjust the selection of the low level heuristics for this bi-objective problem. The two indicators estimate the objective value improvement and the improvement direction over the Pareto Front, respectively. To evaluate the generality of the proposed algorithms, a set of benchmark instances with various features is extracted from real-life historical datasets. The experiment results show that GIHH significantly improves the quality of the final Pareto Solution Set, outperforming the state-of-the-art algorithms for similar problems. Its application on VRPTW also obtains promising results

Hemoglobin, Albumin, Lymphocyte and Platelet Score as a Novel Predictor of Mortality and Rebleeding in Patients with Upper Gastrointestinal Bleeding

Burcu Azapoğlu Kaymak,1 Merve Eksioglu,1 Tuba Cimilli Öztürk,1 Mehmet Köroğlu2 1University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Department of Emergency Medicine, Istanbul, Turkey; 2University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Department of Gastroenterology, Istanbul, TurkeyCorrespondence: Burcu Azapoğlu Kaymak, University of Health Sciences Fatih Sultan Mehmet Education and Research Hospital Department of Emergency Medicine Atasehir-Istanbul, Istanbul, Turkey, Email [email protected]: Upper gastrointestinal bleeding (UGIB) poses significant risks of morbidity and mortality, necessitating effective risk stratification tools. Traditional scoring systems such as the Rockall (RS), Glasgow-Blatchford (GBS), and AIMS65 have limitations in accurately predicting mortality and rebleeding. The Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score, initially developed for cancer prognosis, has demonstrated prognostic value in various conditions. This study aims to evaluate whether the HALP score, when assessed at admission, aligns with the Rockall score and can be used to predict rebleeding and 30- day mortality in UGIB patients.Patients and Methods: This retrospective study included 256 patients with confirmed UGIB admitted to a tertiary hospital in Istanbul, Turkey, between 2017 and 2024. Patient data, including demographics, vital signs, laboratory parameters, endoscopic findings, and clinical outcomes, were collected. The HALP score was calculated at admission to the emergency department. ROC curve analysis assessed the predictive accuracy of the HALP score for 30-day mortality, rebleeding, and its performance was compared with the Rockall score.Results: The predictive performance of the HALP and Rockall scores for 30-day mortality and rebleeding was evaluated using ROC analysis, with AUC values of 0.772 (95% CI: 0.715– 0.822) and 0.770 (95% CI: 0.714– 0.820) for mortality prediction, respectively (p = 0.9801). For rebleeding prediction, the Rockall score had a higher AUC (0.739, 95% CI: 0.681– 0.792) than the HALP score (0.688, 95% CI: 0.627– 0.744), though the difference was not statistically significant (p = 0.2969).Conclusion: The results of this study demonstrate that the HALP score can be used for prognosis prediction in UGIB, exhibiting comparable sensitivity and specificity to the Rockall score. Its ease of calculation using routine laboratory parameters offers a practical complement to existing scoring systems.Keywords: upper gastrointestinal bleeding, HALP score, prognostic scoring, mortality predictio

Comparative Prognostic Accuracy of Clinical and Inflammation- or Nutrition-Based Scores in Older Adults with Community-Acquired Pneumonia

Merve Eksioglu,1 Burcu Azapoglu Kaymak,1 Ebru Unal Akoglu,1 Selman Faruk Akyıldız,1 Ramazan Sivil,2 Tuba Cimilli Ozturk1 1Department of Emergency Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey; 2Department of Emergency Medicine, University of Health Sciences, Antalya Education and Research Hospital, Antalya, TurkeyCorrespondence: Merve Eksioglu, Department of Emergency Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Hastane Sokak No: 1/9 İçerenköy, Ataşehir, Istanbul, 34752, Turkey, Tel +90 216 578 30 00; +90 505 295 36 87, Email [email protected]: This study aimed to assess the prognostic accuracy of the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and C-reactive protein/albumin ratio (CAR) in predicting 30-day mortality and intensive care unit (ICU) admission compared with the Pneumonia Severity Index (PSI) and CURB-65 in older adults with community-acquired pneumonia (CAP).Patients and Methods: This retrospective, single-center cohort study was conducted in a tertiary emergency department. Patients aged ≥ 65 years with CAP were included. Exclusion criteria were hospital- or ventilator-associated pneumonia, pneumonia mimics, and immunocompromised status. GPS and mGPS were calculated using CRP > 10 mg/L and albumin < 35 g/L. ROC and logistic regression analyses were performed.Results: A total of 349 patients (mean age: 77.96 ± 8.42 years; 52.7% men) were included. The 30-day mortality and ICU admission rates were 19.5% and 27.2%, respectively. For predicting mortality, the GPS showed an AUC of 0.753 (95% CI: 0.690– 0.816), sensitivity of 75.0%, specificity of 73.3%, PPV of 43.9%, and NPV of 92.4%. mGPS had an AUC of 0.747 (95% CI: 0.679– 0.814), sensitivity 77.9%, specificity 73.3%, PPV 45.2%, and NPV 93.2%. The CAR yielded an AUC of 0.677 (95% CI: 0.604– 0.751), sensitivity of 82.4%, specificity of 45.6%, PPV of 29.5%, and NPV of 91.4%. For ICU admission, the AUCs were 0.770 (GPS), 0.757 (mGPS), and 0.676 (CAR). The PSI demonstrated the highest predictive accuracy (AUC: 0.884 for mortality, 0.919 for ICU admission), followed by CURB-65 (AUC: 0.848 and 0.879, respectively). Independent predictors of 30-day mortality included acute confusion, lower PaO2/FiO2 ratio, low systolic blood pressure, reduced hemoglobin levels, and Alzheimer’s disease or dementia.Conclusion: The PSI and CURB-65 demonstrated superior prognostic accuracy. GPS and mGPS showed moderate performance, whereas CAR exhibited the lowest overall discriminative ability for both outcomes.Keywords: geriatric emergency care, community-acquired pneumonia, prognostic scores, pneumonia severity index, PSI, glasgow prognostic score, GPS, C-reactive protein to albumin ratio, CA

TREATMENT, DISEASE CONTROL, QUALITY OF LIFE AND PSYCHOLOGICAL STATUS IN PATIENTS WITH ANKYLOSING SPONDYLITIS DURING THE COVID-19 PANDEMIC

Introduction. The coronavirus disease (COVID-19) pandemic has the potential to impact disease activity and psychological well-being in people with rheumatic diseases. This study aimed to compare ankylosing spondylitis (AS) patients with and without COVID-19 history in terms of treatment, disease control, quality of life and psychological status by providing a cross-sectional look at treatment, disease control, quality of life and psychological status in patients with AS during the COVID-19 pandemic. Methods. The study included 74 AS patients, in two groups based on COVID-19 history. Demographic data and clinical characteristics were recorded. Treatment, disease control, functional status, and quality of life were evaluated using Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (BASFI), and impact of COVID-19 on quality-of-life scales. Psychological status was assessed using the Beck Depression Inventory, Beck Hopelessness Scale, and COVID-19 anxiety scale. Results. Of the 74 patients diagnosed with AS, 44 were female and 34 were male. The mean age was 47.3 years. In total, 35 patients (47.3%) had COVID-19. We found that the group without COVID-19 had significantly higher levels of hypothyroidism than the other group (p = 0.008). The BASFI value was significantly higher in the COVID-19 group (p = 0.031). The group with COVID-19 had a substantially higher rate of continuing non-anti-rheumatic drug use than the other group (p = 0.02). Conclusion. During COVID-19 pandemic period, the majority of patients continued their medication, so treatment and disease control were not negatively affected. Having COVID-19 did not cause a significant difference psychologically

Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells

The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features.The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication.HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I.These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection

DCs Pulsed with Novel HLA-A2-Restricted CTL Epitopes against Hepatitis C Virus Induced a Broadly Reactive Anti-HCV-Specific T Lymphocyte Response

OBJECTIVE: To determine the capacity of dendritic cells (DCs) loaded with single or multiple-peptide mixtures of novel hepatitis C virus (HCV) epitopes to stimulate HCV-specific cytotoxic T lymphocyte (CTL) effector functions. METHODS: A bioinformatics approach was used to predict HLA-A2-restricted HCV-specific CTL epitopes, and the predicted peptides identified from this screen were synthesized. Subsequent IFN-γ ELISPOT analysis detected the stimulating function of these peptides in peripheral blood mononuclear cells (PBMCs) from both chronic and self-limited HCV infected subjects (subjects exhibiting spontaneous HCV clearance). Mature DCs, derived in vitro from CD14(+) monocytes harvested from the study subjects by incubation with appropriate cytokine cocktails, were loaded with novel peptide or epitope peptide mixtures and co-cultured with autologous T lymphocytes. Granzyme B (GrB) and IFN-γ ELISPOT analysis was used to test for epitope-specific CTL responses. T-cell-derived cytokines contained in the co-cultured supernatant were detected by flow cytometry. RESULTS: We identified 7 novel HLA-A2-restricted HCV-specific CTL epitopes that increased the frequency of IFN-γ-producing T cells compared to other epitopes, as assayed by measuring spot forming cells (SFCs). Two epitopes had the strongest stimulating capability in the self-limited subjects, one found in the E2 and one in the NS2 region of HCV; five epitopes had a strong stimulating capacity in both chronic and self-limited HCV infection, but were stronger in the self-limited subjects. They were distributed in E2, NS2, NS3, NS4, and NS5 regions of HCV, respectively. We also found that mDCs loaded with novel peptide mixtures could significantly increase GrB and IFN-γ SFCs as compared to single peptides, especially in chronic HCV infection subjects. Additionally, we found that DCs pulsed with multiple epitope peptide mixtures induced a Th1-biased immune response. CONCLUSIONS: Seven novel and strongly stimulating HLA-A2-restricted HCV-specific CTL epitopes were identified. Furthermore, DCs loaded with multiple-epitope peptide mixtures induced epitope-specific CTLs responses