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ABSTRACT: Background: Cardiovascular magnetic resonance (CMR) phase contrast is used to quantify blood flow. We sought to develop a complex-difference reconstruction for inline super-resolution of phase-contrast flow (CRISPFlow) to accelerate phase-contrast imaging. Methods: CRISPFlow was built on the super-resolution generative adversarial network. The model was trained and tested (4:1 ratio) using retrospectively identified phase-contrast images from 2020 patients (56 ± 16 years; 1131 men) referred for clinical 3T CMR at a single center from 2018 to 2023. For testing, ascending aortic flow images collected with 2.5 × 1.9 mm2 resolution using generalized autocalibrating partially parallel acquisitions (GRAPPA) were used to synthesize images with 7.5 × 1.9 mm2 resolution. CRISPFlow subsequently restored spatial resolution. In a prospective validation study of 38 participants (57 ± 15 years; 14 men) and 16 healthy individuals (42 ± 16 years; 6 men), CRISPFlow was applied to phase-contrast images collected with 7.5 × 1.9 mm2 resolution with use of GRAPPA and was compared to GRAPPA-accelerated images collected with 2.3 × 1.9 mm2 resolution. A blur metric was used to quantify sharpness. Aortic flow measurements were obtained semi-automatically. Statistical evaluation included analysis of variance, Bland-Altman analysis, and Pearson correlation coefficient (r). Results: CRISPFlow reconstruction was successful in all cases. CRISPFlow reduced blurring in retrospective (0.35 vs 0.47, P 0.90) between GRAPPA and CRISPFlow measurements of flow in both studies. Conclusion: We demonstrated the potential of CRISPFlow to accelerate phase contrast CMR.

ABSTRACT: Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging enables imaging of scar/fibrosis and is a cornerstone of most CMR imaging protocols. CMR imaging can benefit from image acceleration; however, image acceleration in LGE remains challenging due to its limited signal-to-noise ratio. In this study, we sought to evaluate a rapid two-dimensional (2D) LGE imaging protocol using a generative artificial intelligence (AI) algorithm with inline reconstruction. Methods: A generative AI-based image enhancement was used to improve the sharpness of 2D LGE images acquired with low spatial resolution in the phase-encode direction. The generative AI model is an image enhancement technique built on the enhanced super-resolution generative adversarial network. The model was trained using balanced steady-state free-precession cine images, readily used for LGE without additional training. The model was implemented inline, allowing the reconstruction of images on the scanner console. We prospectively enrolled 100 patients (55 ± 14 years, 72 males) referred for clinical CMR at 3T. We collected three sets of LGE images in each subject, with in-plane spatial resolutions of 1.5 × 1.5-3-6 mm2. The generative AI model enhanced in-plane resolution to 1.5 × 1.5 mm2 from the low-resolution counterparts. Images were compared using a blur metric, quantifying the perceived image sharpness (0 = sharpest, 1 = blurriest). LGE image sharpness (using a 5-point scale) was assessed by three independent readers. Results: The scan times for the three imaging sets were 15 ± 3, 9 ± 2, and 6 ± 1 s, with inline generative AI-based images reconstructed time of ∼37 ms. The generative AI-based model improved visual image sharpness, resulting in lower blur metric compared to low-resolution counterparts (AI-enhanced from 1.5 × 3 mm2 resolution: 0.3 ± 0.03 vs 0.35 ± 0.03, P

Akyl urea derivatives, either symmetrical or unsymmetrical in nature possessing a free N-H or N-alkyl moieties in the molecular framework of urea governs the excited state properties of acridinedione dye (ADR1) which is a resorcinol-based derivative. Fluorescence enhancement (FE) of ADR1 dye is observed on the addition of unsymmetrical urea derivatives, whereas a decrease in the fluorescence intensity resulted upon the addition of symmetrical urea derivatives. The nature of the urea derivatives controls the suppression of photoinduced electron transfer (PET) via space, which is the cause of the FE. FQ results from the donor and acceptor moieties of ADR1 dye promoting the PET process. Urea (U), symmetrical and unsymmetrical urea derivatives (except Tetramethyl urea (TMU)) results no significant shift of the localized excited (LE) state emission of ADR1 dye. Studies of the ADR1 dye’s fluorescence lifetime in the presence of urea compounds show a significant increase in lifetime. This phenomenon is explained by a significant difference in the hydrogen-bonding (HB) pattern, which causes variation in the microenvironment created by the solute molecules in the aqueous phase. Both the hydrophobic effects of the alkyl group substituents in the urea molecular framework and the HB interactions between the solute and solvent influence the excited state features of ADR1 dye. Further, the role of urea derivatives and ADR1 dye (both are considered as competitive guest molecules) energetics and molecular interactions were studied in the presence of host molecule, Human Serum Albumin (HSA). The binding energy (BE) and several bimolecular interactions driven by urea derivatives in the presence of ADR1-HSA complex in comparison with that of urea derivatives-HSA complex were investigated by molecular docking (Mol.Doc) methodology. Incorporating theoretical research along with steady state and time-resolved fluorescence investigations proved to be an effective method to evaluate the interactions of competing solutes comprising both hydrophobic and HB functional groups.

Diesel engine parameters, such as fuel and its additives, play an essential role in minimising the effects of engine vibration. This study aimed to use artificial neural networks (ANN) to model and analyse diesel engine vibration characteristics at different engine speeds using NH3 as an additive in hazelnut (HD), peanut (PD), and waste-cooking oil (WD) biodiesels. The results showed good correlations between the ANN models and experimental results using regression analysis methods. The ANN models for diesel engines showed high accuracy. The ANN models indicated that a 5 % NH3 additive decreased engine vibration for HD and PD.In comparison, 10 % and 15 % NH3 additive ratios increased engine vibration for HD, PD, and WD due to low combustion quality. The lowest vibration levels occurred with P100, P95A5, P90A10, and P85A15 at 1200 rpm. H100 and H95A5 produced the highest diesel engine resultant vibration (DERV) values. All ANN models generated the lowest and highest DERV values at 1200 rpm and 2100 rpm, respectively. The RMS method showed that H95A5, P85A15, and W85A15 contributed the most to diesel engine vibration. Using a low amount of NH3 additive positively affected DERV for HD and PD but not for WD.

Summary: Nociceptive axons undergo remodeling as they innervate their targets during development and in response to environmental insults and pathological conditions. How is nociceptive morphogenesis regulated? Here, we show that the microtubule destabilizer kinesin family member 2A (Kif2a) is a key regulator of nociceptive terminal structures and pain sensitivity. Ablation of Kif2a in sensory neurons causes hyperinnervation and hypersensitivity to noxious stimuli in young adult mice, whereas touch sensitivity and proprioception remain unaffected. Computational modeling predicts that structural remodeling is sufficient to explain the phenotypes. Furthermore, Kif2a deficiency triggers a transcriptional response comprising sustained upregulation of injury-related genes and homeostatic downregulation of highly specific channels and receptors at the late stage. The latter effect can be predicted to relieve the hyperexcitability of nociceptive neurons, despite persisting morphological aberrations, and indeed correlates with the resolution of pain hypersensitivity. Overall, we reveal a critical control node defining nociceptive terminal structure, which is regulating nociception.

A large portion of the country of Turkey is located in a very high seismic region known as a first-degree earthquake zone where earthquakes occur frequently. Earthquakes result in damage to infrastructure including base station towers and subsequently failure of mobile communication networks. The loss of functionality of mobile communication networks following an earthquake has a direct impact on emergency response and both short and long-term recovery phases. Understanding both these phases requires systematic modeling of infrastructure components, which rely on fragility curves representing the probabilistic relationship between seismic intensity and damage. This study focuses on the development of damage fragility curves (fragilities) for an archetypical mobile cellular tower, namely a 55 m tall steel lattice tower (SLT) used in base station towers in Turkey. Nonlinear time history analysis was performed using a robust suite of far field ground motion records to model the performance of the archetype tower and develop damage fragilities for five specific damage states which were defined in terms of likely performance: damage state 0 (no damage), damage state 1 (uninterrupted communication), damage state 2 (communication interruption), damage state 3 (communication failure), damage state 4 (structural failure). While fragility curve has been developed for lattice towers of different types and sizes in the literature, there is no specific study for 55 m SLT and the novelty of this study is that the resulting SLT archetype fragilities can serve as a benchmark dataset for use in community-level risk and resilience analyses to improve response and recovery planning following earthquakes.

Background: Inhibitory control (IC) deficits have been proposed as a potential risk factor for depression. However, little is known about the intra-individual daily fluctuations in IC, and its relationship to mood and depressive symptoms. Here, we examined the everyday association between IC and mood, in typical adults with various levels of depressive symptoms. Methods: Participants (N = 106) reported their depressive symptoms and completed a Go-NoGo (GNG) task measuring IC at baseline. Then, they completed a 5-day ecological-momentary-assessment (EMA) protocol, in which they reported their current mood and performed a shortened GNG task twice/day using a mobile app. Depressive symptoms were measured again following the EMA. Hierarchical-linear-modeling (HLM) was applied to examine the association between momentary IC and mood, with post-EMA depressive symptoms as a moderator. Results: Individuals with elevated depressive symptoms demonstrated worse and more variable IC performance over the EMA. In addition, post-EMA depressive symptoms moderated the association between momentary IC and daily mood, such that reduced IC was associated with more negative mood only for those with lower, but not higher, symptoms. Limitations: Future investigations should examine the validity of these outcomes in clinical samples, including patients with Major Depressive Disorder. Conclusions: Variable, rather than mere reduced, IC, is related to depressive symptoms. Moreover, the role of IC in modulating mood may differ in non-depressed individuals and individuals with sub-clinical depression. These findings contribute to our understanding of IC and mood in real life and help account for some of the discrepant findings related to cognitive control models of depression.

A study was conducted on six animal feed centers in Israel where fungal and mycotoxin presence was examined in maize and wheat silages. Fumonisin mycotoxins FB1 and FB2 were present in every maize silage sample analyzed. Interestingly, no correlation was found between the occurrence of specific mycotoxins and the presence of the fungal species that might produce them in maize and wheat silages. We further investigated the effect of pomegranate peel extract (PPE) on Fusarium infection and fumonisin biosynthesis in laboratory-prepared maize silage. PPE had an inhibitory effect on FB1 and FB2 biosynthesis by Fusarium proliferatum, which resulted in up to 90 % reduction of fumonisin production in silage samples compared to untreated controls. This finding was supported by qRT-PCR analysis, showing downregulation of key genes involved in the fumonisin-biosynthesis pathway under PPE treatment. Our results present promising new options for the use of natural compounds that may help reduce fungal and mycotoxin contamination in agricultural foodstuff, and potentially replace traditionally used synthetic chemicals.

Objective: No prior study has investigated the relation of primary dysmenorrhea (PD) with attention deficit hyperactivity disorder (ADHD) symptoms in adolescent age groups. This study aimed to investigate the relationship of PD with ADHD and psychological symptoms among adolescents. Another objective was to examine the PD related non-psychogenic factors and sleep quality. Materials and methods: Two hundred nine adolescent girls who applied to policlinics for various reasons were enrolled. All participants completed self-report questionnaires. Questionnaire for sociodemographic data, menstrual pattern and dysmenorrhea in adolescents, Visual analog scale, Pittsburgh Sleep Quality Index, DSM-5 Level 2 Sleep Disorders Scale, Brief Symptom Inventory, and the Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition-Based Child and Adolescent Disruptive Behavior Disorders Screening and Rating Scale were used to measure outcomes. Results: A hundred and four (49.8%) adolescents reported having pain that affects daily activities during menstruation. These adolescents had worse sleep quality, more inattention and hyperactivity-impulsivity problems, and other psychological symptoms of anxiety, depression, somatization, negative self-perception, and hostility in comparison to others (P

Aim: This study aimed to examine the relationship between death anxiety in schizophrenia patients and the clinical characteristics of the disease and its functionality. Method: The study included 52 patients diagnosed with schizophrenia according to the DSM-5 diagnostic criteria and 52 healthy volunteers. Death anxiety scores were compared between the two groups using the Abdel-Khalek Death Anxiety Scale (ADAS). The functionality of the schizophrenia patients was evaluated with the Functional Remission of General Schizophrenia (FROGS) scale. Results: The mean ADAS total scores were statistically significantly higher in the schizophrenia patient group than in the control group. A low-level negative correlation was determined between the ADAS total points and the FROGS total points, the FROGS subscales of daily life skills and health. Conclusion: The results of this study showed higher death anxiety in schizophrenia patients than in the healthy control group. Patients with a higher level of functionality were determined to have a lower level of death anxiety. These results support our idea that interventions and therapeutic approaches to increase functionality in patients with schizophrenia can reduce their death anxiety. In order to reach more evident conclusions on this subject, prospective studies that deal with the causal relationship between death anxiety and functionality are needed.

Parallel imaging is the most clinically used acceleration technique for magnetic resonance imaging (MRI) in part due to its easy inclusion into routine acquisitions. In k-space based parallel imaging reconstruction, sub-sampled k-space data are interpolated using linear convolutions. At high acceleration rates these methods have inherent noise amplification and reduced image quality. On the other hand, non-linear deep learning methods provide improved image quality at high acceleration, but the availability of training databases for different scans, as well as their interpretability hinder their adaptation. In this work, we present an extension of Robust Artificial-neural-networks for k-space Interpolation (RAKI), called residual-RAKI (rRAKI), which achieves scan-specific machine learning reconstruction using a hybrid linear and non-linear methodology. In rRAKI, non-linear CNNs are trained jointly with a linear convolution implemented via a skip connection. In effect, the linear part provides a baseline reconstruction, while the non-linear CNN that runs in parallel provides further reduction of artifacts and noise arising from the linear part. The explicit split between the linear and non-linear aspects of the reconstruction also help improve interpretability compared to purely non-linear methods. Experiments were conducted on the publicly available fastMRI datasets, as well as high-resolution anatomical imaging, comparing GRAPPA and its variants, compressed sensing, RAKI, Scan Specific Artifact Reduction in K-space (SPARK) and the proposed rRAKI. Additionally, highly-accelerated simultaneous multi-slice (SMS) functional MRI reconstructions were also performed, where the proposed rRAKI was compred to Read-out SENSE-GRAPPA and RAKI. Our results show that the proposed rRAKI method substantially improves the image quality compared to conventional parallel imaging, and offers sharper images compared to SPARK and ℓ1-SPIRiT. Furthermore, rRAKI shows improved preservation of time-varying dynamics compared to both parallel imaging and RAKI in highly-accelerated SMS fMRI.

Leishmaniasis causes the ninth largest disease burden among infectious diseases but remains a very neglected tropical disease. Although the disease is endemic in Cameroon and some neighboring countries, data on its epidemiology are very scanty. The present review summarizes the available information on leishmaniasis in the central region of Africa. According to available records, Cameroon, Chad and Nigeria have been identified as endemic foci of both cutaneous (CL) and visceral leishmaniasis (VL). In addition, the phlebotomine vectors of leishmaniasis have been reported in these three countries and also in Congo and the Central African Republic. Although Gabon, Central African Republic, Equatorial Guinea and Congo are all situated next to the above leishmaniasis-endemic countries and are characterized by similar landscapes and vegetation, they lack published reports of autochthonous cases of leishmaniasis. Considering that many cases of the disease might remain unreported, it might not be an overstatement to recommend that research should be carried out in Gabon, Equatorial Guinea, Central African Republic and Congo to identify cases of leishmaniasis (CL and/or VL), the parasite and vector species, and the mammalian reservoir host. This review updates data on leishmaniasis and its insect vector in the geographical region of Central Africa. Such updates are basic requirement for the development of successful control programmes in individual countries and the whole region. In order to address the shortcomings identified in the present review, the authors recommend training of more scientists in leishmaniasis epidemiology in the region that should be accompanied by necessary funding. This training must be multidisciplinary and include development of laboratory and field skills for studies of the parasite, the vector, the reservoir, the vegetation and the soil in potential endemic foci. In addition, prospective studies involving geographers and other experts should develop a disease risk map of the Central Africa region.

Summary: Microglia play a key role in innate immunity in Alzheimer disease (AD), but their role as antigen-presenting cells is as yet unclear. Here we found that amyloid β peptide (Aβ)-specific T helper 1 (Aβ-Th1 cells) T cells polarized to secrete interferon-γ and intracerebroventricularly (ICV) injected to the 5XFAD mouse model of AD induced the differentiation of major histocompatibility complex class II (MHCII)+ microglia with distinct morphology and enhanced plaque clearance capacity than MHCII− microglia. Notably, 5XFAD mice lacking MHCII exhibited an enhanced amyloid pathology in the brain along with exacerbated innate inflammation and reduced phagocytic capacity. Using a bone marrow chimera mouse model, we showed that infiltrating macrophages did not differentiate to MHCII+ cells following ICV injection of Aβ-Th1 cells and did not support T cell-mediated amyloid clearance. Overall, we demonstrate that CD4 T cells induce a P2ry12+ MHCII+ subset of microglia, which play a key role in T cell-mediated effector functions that abrogate AD-like pathology. : Biological Sciences; Neuroscience; Immunology; Cell Biology Subject Areas: Biological Sciences, Neuroscience, Immunology, Cell Biology

Background: The delivery of therapeutic proteins to selected sites within the central nervous system (CNS) parenchyma is a major challenge in the treatment of various neurodegenerative disorders. As brain-derived neurotrophic factor (BDNF) is reduced in the brain of people with Alzheimer's disease (AD) and its administration has shown promising therapeutic effects in mouse model of the disease, we generated a novel platform for T cell-based BDNF delivery into the brain parenchyma. Methods: We generated amyloid beta-protein (Aβ)-specific CD4 T cells (Aβ-T cells), genetically engineered to express BDNF, and injected them intracerebroventricularly into the 5XFAD mouse model of AD. Findings: The BDNF-secreting Aβ-T cells migrated efficiently to amyloid plaques, where they significantly increased the levels of BDNF, its receptor TrkB, and various synaptic proteins known to be reduced in AD. Furthermore, the injected mice demonstrated reduced levels of beta-secretase 1 (BACE1)—a protease essential in the cleavage process of the amyloid precursor protein—and ameliorated amyloid pathology and inflammation within the brain parenchyma. Interpretation: A T cell-based delivery of proteins into the brain can serve as a platform to modulate neurotoxic inflammation and to promote neuronal repair in neurodegenerative diseases. Keywords: Cell-based delivery, CD4 T cell, BDNF, CNS, Brain, Alzheimer's disease, Amyloid plaques, Targeted drug delivery

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 appeared in Wuhan, China in December 2019 and quickly spread around the world and is considered a global pandemic. This disease, which is pre-infected with respiratory and cardiovascular system symptoms, can also occur in many organ systems. Since the beginning of the pandemic, cases related to neurological involvement have been reported in the literature and studies coercing neurological findings and complications have been published. COVID-19 can cause wide spectrum of neurological phenotypes from severe to milder. To the best of our knowledge, our case is the first report describing the chorea in a patient associated with COVİD-19. In this article, we aim to present a patient who was admitted with chorea on the 3rd day of the COVID-19 followed by Sydenham chorea, which had already improved. This report expands the phenotypic spectrum of COVID-19 and suggests that COVID-19 can be associated with or trigger chorea.

The roots of Valeriana officinalis L. (Valerianaceae) are used for treating sleep disorders and/or mild nerve tension. The effect of valerenic acid on brain-derived neurotrophic factor (BDNF) has not yet been studied, although it is known that gamma-amino butyric acid A (GABAA) receptor is regulated by BDNF, which modulates the depressive-like behavior and neurogenesis. The purpose of this study is to determine the effect of V. officinalis root extract (VO), its main constituents valerenic acid (VA) and acetoxy valerenic acid (AVA) as well as valerenic acid-free (VAF), acetoxy valerenic acid-free (AVAF) extracts and increasing amounts of valerenic acid containing extracts on the BDNF expression in SH-SY5Y cell lines. The effect of methanolic extracts of VO, VA, AVA, VAF, AVAF, and the extracts whose amount of VA were increased gradually, were tested using a Human BDNF ELISA kit with 17β-estradiol as a positive control. The VO and VA extracts caused a significant (p

Purpose: Ischemia–reperfusion injury is one of the consequences of tourniquet application for extremity surgery. The aim of the study was to establish the effect of dexmedetomidine on the acute lung injury following lower extremity experimental ischemia–reperfusion model in rats. Methods: Twenty-eight Wistar-Albino breed Rats were recruited after Ethics Committee approval and allocated into 4 groups, each with 7 subjects. Group 1 (SHAM) received only anesthesia. Group 2 (IR) had experienced 3 h of ischemia and 3 h of reperfusion using left lower extremity tourniquet after anesthesia application. Groups 3 (D-50) and 4 (D-100) had undergone the same procedures as in the Group 2, except for receiving 50 and 100 mg·kg−1, respectively, dexmedetomidine intraperitoneally 1 h before the tourniquet release. Blood samples were obtained for the analysis of tumor necrosing factor-α and interleukin-6. Pulmonary tissue samples were obtained for histological analysis. Results: No significant difference regarding blood tumor necrosing factor-α and interleukin-6 values was found among the groups, whereas pulmonary tissue injury scores revealed significant difference. Histological scores obtained from the Group 2 were significantly higher from those in the Groups 1, 3 and 4 with p-values 0.001 for each comparison. Moreover, Group 1 scores were found to be significantly lower than those in the Groups 3 and 4 with p-values 0.001 and 0.011, respectively. No significant difference was observed between the Groups 3 and 4. Conclusion: Dexmedetomidine is effective in reduction of the experimental ischemia–reperfusion induced pulmonary tissue injury in rats, formed by extremity tourniquet application. Resumo: Objetivo: A lesão de isquemia-reperfusão é uma das consequências da aplicação do torniquete em cirurgias de extremidades. O objetivo do estudo foi determinar o efeito de dexmedetomidina em lesão pulmonar aguda após modelo experimental de isquemia-reperfusão em extremidade inferior de ratos. Métodos: Vinte e oito ratos albinos Wistar foram recrutados após aprovação do Comitê de Ética e alocados em quatro grupos, cada um com sete indivíduos. O Grupo 1 (Sham) recebeu apenas anestesia. O Grupo 2 (IR) foi submetido a 3 horas de isquemia e 3 horas de reperfusão com o uso de torniquete em extremidade inferior após a aplicação da anestesia. Os grupos 3 (D-50) e 4 (D-100) foram submetidos aos mesmos procedimentos do Grupo 2, exceto por receberem 50 e 100 mg·kg−1 de dexmedetomidina, respectivamente, por via intraperitoneal 1 hora antes da liberação do torniquete. Amostras de sangue foram coletadas para análise de TNF-α e Interleucina-6 (IL-6). Amostras de tecido pulmonar foram coletadas para análise histológica. Resultados: Não houve diferença significativa quanto aos valores sanguíneos de TNF-α e IL-6 entre os grupos, enquanto os escores de lesão em tecidos pulmonares revelaram diferença significativa. Os escores histológicos obtidos no Grupo 2 foram significativamente maiores que os dos grupos 1, 3 e 4, com valores-p de 0,001 para cada comparação. Além disso, os escores do Grupo 1 foram significativamente menores que os dos grupos 3 e 4, com valores-p de 0,001 e 0,011, respectivamente. Não houve diferença significativa entre os grupos 3 e 4. Conclusão: Dexmedetomidina mostrou eficácia na redução de lesão em tecido pulmonar induzida por isquemia-reperfusão experimental em ratos, ocasionada por aplicação de torniquete em extremidade. Keywords: Experimental, Dexmedetomidine, Reperfusion injury, Acute lung injury, Palavras-chave: Experimental, Dexmedetomidina, Lesão de reperfusão, Lesão pulmonar aguda

Atrial fibrillation (AF) usually starts as paroxysmal but can evolve relentlessly to the persistent and permanent forms. However, the mechanisms governing such a transition are unknown. The authors show that intracardiac serum levels of galectin (Gal)-3 are greater in patients with persistent than paroxysmal AF and that Gal-3 independently predicts atrial tachyarrhythmia recurrences after a single ablation procedure. Using a sheep model of persistent AF the authors further demonstrate that upstream therapy targeting Gal-3 diminishes both electrical remodeling and fibrosis by impairing transforming growth factor beta–mediated signaling and reducing myofibroblast activation. Accordingly, Gal-3 inhibition therapy increases the probability of AF termination and reduces the overall burden of AF. Therefore the authors postulate that Gal-3 inhibition is a potential new upstream therapy to prevent AF progression.

Background and objectives: Many conditions such as bacterial and viral infectious diseases, mechanical obstruction due to air and calculi and drugs can cause parotitis. We present a case of unusual bilateral parotitis in a patient under non-invasive continuous positive airway pressure (CPAP) therapy for chronic obstructive pulmonary disease exacerbation in intensive care unit. Case report: A 36-year-old patient was admitted to intensive care unit with the diagnosis of chronic obstructive pulmonary disease exacerbation. Antibiotherapy, bronchodilator therapy and non-invasive positive pressure ventilation were applied as treatment regimen. Painless swellings developed on the 3rd day of admission on the right and a day after this on the left parotid glands. Amylase levels were increased and ultrasonographic evaluation revealed bilateral parotitis. No intervention was made and the therapy was continued. The patient was discharged on the 6th day with clinical improvement and regression of parotid swellings without any complications. Conclusions: Parotitis may have occurred after retrograde air flow in the Stensen duct during CPAP application. After the exclusion of possible viral and bacteriological etiologies and possible drug reactions we can focus on this diagnosis. Resumo: Justificativa e objetivos: Muitas condições podem causar parotidite, incluindo doenças infecciosas virais e bacterianas, obstrução mecânica por causa da presença de ar, cálculos e medicamentos. Apresentamos um caso de parotidite bilateral incomum em um paciente sob tratamento com pressão positiva contínua não invasiva das vias aéreas (PPCVA) para exacerbação da doença pulmonar obstrutiva crônica em unidade de terapia intensiva. Relato de caso: Paciente de 36 anos, internado em unidade de terapia intensiva com diagnóstico de exacerbação da doença pulmonar obstrutiva crônica. Antibioterapia, terapia broncodilatadora e ventilação com pressão positiva não invasiva foram aplicadas como regime de tratamento. No terceiro dia de internação, inchaços indolores desenvolveram-se à direita da glândula parótida e, depois, à esquerda. Os níveis de amilase aumentaram e o exame ultrassonográfico revelou parotidite bilateral. Nenhuma intervenção foi feita e o tratamento foi continuado. O paciente recebeu alta no sexto dia, com melhoria clínica e regressão do inchaço da parótida, sem complicações. Conclusões: A parotidite pode ter ocorrido após o fluxo retrógrado de ar do duto de Stensen durante a aplicação de PPCVA. Após a exclusão de possíveis etiologias virais e bacteriológicas e possíveis reações medicamentosas, podemos focar no diagnóstico. Keywords: Parotitis, Bilateral parotitis, Pneumoparotitis, Continuous positive airway pressure, Palavras-chave: Parotidite, Parotidite bilateral, Pneumoparotidite, Pressão positiva contínua das vias aéreas

Background. In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection.Material and methods. A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD.Results. Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups.Conclusion. In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.

The results of the acute exacerbations of hepatitis B virus are varied from silent to severe acute hepatitis. HBsAg seroconversion induced by either antiviral drugs or occurred spontaneously, as a targeted end point of HBV infection management is infreaquent. The affect of the severe hepatitic flare on HBsAg seroconversion was reported before, however the predictive markers of HBsAg seroconversion are not clear yet. The reasons of the spontaneously HBV re-activations, or its usual results are not known well. We, herein reported a case, with the high serum HBV DNA titer during an acute spontaneously induced severe exacerbation of HBV infection which spontaneously resulted in total HBV recovery.

Mucormycosis is an acutely fatal infection that occurs in immuncompromised patients. Cirrhosis is an acquired immune deficiency state and those patients are more prone to develop opportunistic infections. A 42-years-old cirrhotic man was admitted to our gastroenterology clinic with hepatic encephalopathy. Although he recovered from encephalopathy with supportive measurements, he developed paresthesia on the face. He was diagnosed with rhinocerebral mucormycosis and antifungal therapy was administered. Surgical treatment couldn’t be performed because of his bleeding diathesis and poor general condition. He succumbed on the 12th day of his admission.

Background Aims: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited., Objective: We compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors., Methods: A retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion., Results: Of 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome., Conclusions: Immune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors., (Published by Elsevier Inc.)

In this work, dual-template molecularly imprinted polymer surfaces imprinted on blue fluorescent Cr-based MOF (Cr-MOF) functionalized with yellow emissive carbon dots (Y-CDs) were prepared using l-ascorbic acid (AA) and uric acid (UA) as templates for simultaneous selective recognition of AA and UA. The as-prepared nanocomposite probe (Y-CDs/Cr-MOF@MIP) contains two recognition site cavities and emits a dual well-resolved fluorescence spectra when excited at 390 nm; blue emission (λ em 450 nm) is due to Cr-MOF, and yellow emission (λ em 560 nm) is due to Y-CDs. The yellow fluorescence emission of Y-CDs was quenched upon the addition of ascorbic acid, while Cr-MOF's emission remained unaffected. In the same way, the blue fluorescence emission of the Cr-MOFs was quenched in the presence of uric acid, while the yellow emission remained constant. Both emissions were quenched in a sample containing both AA and UA. This can be exploited to design a dual-template biosensor to detect UA and AA simultaneously. The Y-CDs/Cr-MOF@MIP sensor displayed a dynamic linear response for AA in the range 25.0 µM - 425.0 µM with a detection limit of 1.30 µM, and for UA in the range 25.0 µM - 425.0 µM with a detection limit of 1.10 µM. The dual-target probe Y-CDs/Cr-MOF@MIP was highly selective and sensitive for the detection of UA and AA in human urine samples due to the selectivity of the two recognition sites., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, 13 patients (3.8%) developed another cancer with a total of 16 events (4 hematologic malignancies and 12 solid tumors). The 5-year cumulative incidence of a first subsequent malignancy in the recipients of genetically modified IE cells was 3.6% (95% confidence interval, 1.8% to 6.4%). For 11 of the 16 subsequent tumors, biopsies were available, and no sample was transgene positive by polymerase chain reaction. Replication-competent retrovirus testing of peripheral blood mononuclear cells was negative in the 13 patients with subsequent malignancies tested. Rates of subsequent malignancy were low and comparable to standard chemotherapy. These results suggest that the administration of IE cells genetically modified with γ retroviral vectors does not increase the risk for subsequent malignancy., (© 2022 by The American Society of Hematology.)

Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no dose-limiting toxicity, acute GVHD or cytokine release syndrome. Six of 8 evaluable patients remained in long-term complete remission (median: 46.5 months; range, 9-51). In these individuals we detected an increased frequency of tumor-reactive T cells shortly after infusion, with activity against both targeted and nontargeted, known tumor-associated antigens, indicative of in vivo antigen spreading. By contrast, this in vivo amplification was absent in the 2 patients who experienced relapse. In summary, infusion of donor-derived mLSTs after allogeneic HSCT is feasible and safe and may contribute to disease control, as evidenced by in vivo tumor-directed T-cell expansion. Thus, this approach represents a promising strategy for preventing relapse in patients with ALL., (© 2022 by The American Society of Hematology.)

The prognosis of patients with acute myeloid leukemia (AML) remains dismal, highlighting the need for novel innovative treatment strategies. The application of chimeric antigen receptor (CAR) T-cell therapy to patients with AML has been limited, in particular by the lack of a tumor-specific target antigen. CD70 is a promising antigen to target AML, as it is expressed on most leukemic blasts, whereas little or no expression is detectable in normal bone marrow samples. To target CD70 on AML cells, we generated a panel of CD70-CAR T cells that contained a common single-chain variable fragment (scFv) for antigen detection, but differed in size and flexibility of the extracellular spacer and in the transmembrane and the costimulatory domains. These CD70scFv CAR T cells were compared with a CAR construct that contained human CD27, the ligand of CD70 fused to the CD3ζ chain (CD27z). The structural composition of the CAR strongly influenced expression levels, viability, expansion, and cytotoxic capacities of CD70scFv-based CAR T cells, but CD27z-CAR T cells demonstrated superior proliferation and antitumor activity in vitro and in vivo, compared with all CD70scFv-CAR T cells. Although CD70-CAR T cells recognized activated virus-specific T cells (VSTs) that expressed CD70, they did not prevent colony formation by normal hematopoietic stem cells. Thus, CD70-targeted immunotherapy is a promising new treatment strategy for patients with CD70-positive AML that does not affect normal hematopoiesis but will require monitoring of virus-specific T-cell responses., (© 2021 by The American Society of Hematology.)

Background: We wanted to investigate the effect of X-rays on mononuclear blood cells (MNCs) and red blood cells (RBCs) of radiology technicians exposed to X-rays in hospital., Methods: DNA damage was detected by fluorometric analysis of DNA unwinding. Glutathione levels were measured with enzymatic method in mononuclear blood cells. Glutathione content and catalase (CAT) activity of erythrocytes, and plasma malondialdehyde (MDA) levels were determined by spectrophometric methods., Results: An insignificant increase in plasma malondialdehyde levels and a significant decrease in mononuclear blood cells glutathione levels were observed in nonsmoking radiology technicians. In smoking radiology technicians, on the other hand, in addition to an increase in plasma malondialdehyde levels, DNA damage was also significantly apparent. Besides mononuclear blood cells' glutathione depletion, the glutathione content of red blood cells was also found to be decreased., Conclusion: It can be suggested that smoking seems to augment the toxic effects of radiation.