The impact of APOE ε4 in Alzheimer's disease: a meta-analysis of voxel-based morphometry studies.

Background: Alzheimer's disease (AD) is the most prevalent form of dementia, exerting substantial personal and societal impacts. The apolipoprotein E (APOE) ε4 allele is a known genetic factor that increases the risk of AD, contributing to more severe brain atrophy and exacerbated symptoms. Purpose: We aim to provide a comprehensive review of the impacts of the APOE ε4 allele on brain atrophy in AD and mild cognitive impairment (MCI) as a transitional stage of AD. Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies to identify the patterns of grey matter atrophy in APOE ε4 carriers vs. non-carriers. We obtained coordinate-based structural magnetic resonance imaging (MRI) data for 1135 individuals from 12 studies on PubMed and Google Scholar that met our inclusion criteria. Results: We found significant atrophy in the hippocampus and parahippocampus of APOE ε4 carriers compared to non-carriers, especially within the AD and MCI groups, while healthy controls showed no significant atrophy in these regions. Conclusion: Our meta-analysis sheds light on the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, emphasizing the allele's critical influence on neurodegeneration, especially in the hippocampus. Our findings contribute to the understanding of the disease's pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals with the APOE ε4 allele who are at risk for Alzheimer's Disease.

Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

The Relationship Between Tumor Budding and Patient's Survival in Breast Cancer.

Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. Materials and methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. Results and discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio.

Social learning-based health literacy promotion on the self efficacy and social anxiety of adolescents with type 1 diabetes.

BACKGROUND AND OBJECTIVE: Type 1 diabetes mellitus one of the biggest health concerns around the world, is difficult to manage during adolescence. Among the non-medical methods of controlling this disease is empowerment through self-efficacy. Poor self-efficacy leads to social anxiety and ultimately deficiencies in diabetes. There is also a correlation among health literacy, self-efficacy, and social anxiety. Thus, the present study aimed to evaluate the impact of a literacy promotion training program based on social learning theory on the self-efficacy and social anxiety of adolescents with T1DM. METHODS: The current research is a semi-experimental type that was carried out with the cooperation of 66 adolescents aged 15-18 years with type 1 diabetes in Iran (Tehran, 2022). It has control and intervention groups. The endocrinology and diabetes clinics of the intervention and control groups were randomly selected in a multi-stage manner (endocrine and diabetes clinic of children's medical center hospital for the control group and endocrine and diabetes clinic of Mofid hospital for the intervention group) and the participants were selected by Simple Random Sampling method (draw). The training program designed based on Bandura's social learning theory was used to teach adolescents during seven consecutive sessions of 30-45 min during one week. Questionnaires were completed before and one month after the intervention. Data were analysed in SPSS-25 software. FINDINGS: The intervention for adolescents with T1DM in intervention group compared to the control group had a significant effect on improve health literacy (P<0.001), self-efficacy (P<0.001), and social anxiety (P<0.05). CONCLUSIONS: The results can also be used to improve the capabilities of adolescents with T1DM, reduce and prevent disease complications, and develop operational-educational programs in the centers from which these adolescents receive various services. TRIAL REGISTRATION: IRCT20210422051045N1.

Association between quantitative morphological traits and RAPD molecular markers in pomegranate (Punica granatum L.).

Pomegranate (Punica granatum L.) is very important in terms of horticulture and food around the world. The present research aimed to identify the random amplified polymorphic DNA (RAPD) markers associated with morphological traits in pomegranate genotypes. Significant differences were observed among the studied genotypes based on the recorded traits. The 18 RAPD primers produced a total of 154 polymorphic fragments among genotypes. Using multiple regression analysis between each of the morphological traits and 154 RAPD polymorphic bands, RAPD markers associated with each of the morphological traits were identified. In total, 11 markers showed significant correlations with fruit weight, 9 markers with 100-aril weight, 11 markers with anthocyanin, and 8 markers with total soluble solids. Some markers were associated with more than one morphological trait, showing that the association of a marker with more than one trait can be caused by the pleiotropic effects of quantitative trait loci related to each other in different traits. For instance, the BA6-1 marker showed positive correlations with fruit weight, fruit crown width, and leaf length. Also, OPG13-3 and BA6-10 markers showed positive correlations with total soluble solids and anthocyanin content. The informative markers identified related to morphological characteristics in pomegranate can be a suitable guide to identify the genotypes with valuable fruit traits. Also, these markers can be used in selecting suitable parents for population generation for mapping purposes.

A comparative study of GNN and MLP based machine learning for the diagnosis of Alzheimer's Disease involving data synthesis.

Alzheimer's Disease (AD) is a neurodegenerative disease that commonly occurs in older people. It is characterized by both cognitive and functional impairment. However, as AD has an unclear pathological cause, it can be hard to diagnose with confidence. This is even more so in the early stage of Mild Cognitive Impairment (MCI). This paper proposes a U-Net based Generative Adversarial Network (GAN) to synthesize fluorodeoxyglucose - positron emission tomography (FDG-PET) from magnetic resonance imaging - T1 weighted imaging (MRI-T1WI) for further usage in AD diagnosis including its early-stage MCI. The experiments have displayed promising results with Structural Similarity Index Measure (SSIM) reaching 0.9714. Furthermore, three types of classifiers are developed, i.e., one Multi-Layer Perceptron (MLP) based classifier, two Graph Neural Network (GNN) based classifiers where one is for graph classification and the other is for node classification. 10-fold cross-validation has been conducted on all trials of experiments for classifier comparison. The performance of these three types of classifiers has been compared with the different input modalities setting and data fusion strategies. The results have shown that GNN based node classifier surpasses the other two types of classifiers, and has achieved the state-of-the-art (SOTA) performance with the best accuracy at 90.18% for 3-class classification, namely AD, MCI and normal control (NC) with the synthesized fluorodeoxyglucose - positron emission tomography (FDG-PET) features fused at the input level. Moreover, involving synthesized FDG-PET as part of the input with proper data fusion strategies has also proved to enhance all three types of classifiers' performance. This work provides support for the notion that machine learning-derived image analysis may be a useful approach to improving the diagnosis of AD.

Dual-Ligand Strategy for the Design and Construction of a Cd-Zn Heterometallic Metal-Organic Framework by One-Pot Synthesis as a Heterogeneous Catalyst for the Epoxidation Reaction of Olefins.

The use of metal-organic frameworks (MOFs) as catalysts is reported in various industrial applications. In contrast to monometallic MOFs, heterometallic MOFs with mixed organic ligands showed enhanced catalytic properties. The catalytic properties of heterometallic MOFs can be enhanced by generating defects and the synergistic effect between the two heterometals at secondary building units. By using a solvothermal technique, a Cd-Zn heterometallic MOF with a new morphology, [Cd2Zn(DPTTZ)0.5(OBA)3(H2O)(HCOOH)] (IUST-4) [DPTTZ = 2,5-di(4-pyridyl)thiazolo[5,4-d]thiazole, OBA = 4,4'-oxybis(benzoic acid)], was synthesized via a mixed-ligand strategy and characterized by single-crystal and powder X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. X-ray crystallographic analysis showed that IUST-4 is a neutral 3D metal-organic framework crystallized in the monoclinic system with space group C2/c. In this study, the catalytic properties of IUST-4 for the epoxidation of cyclooctene were investigated. IUST-4 was selected as the optimal catalyst for epoxy product production due to its high selectivity and yield. Moreover, the catalytic performance of IUST-4 was maintained despite five recycling cycles without significant degradation. The epoxidation of cyclooctene with IUST-4 has several advantages, including good selectivity, easy recovery, and short-time reaction.

Relationship between molecular markers and important fruit-related traits in almond (Prunus dulcis [Mill.] D.A. Webb syn. P. amygdalus Batsch) as revealed using multiple regression analysis (MRA).

Almond (Prunus dulcis [Mill.] D.A. Webb syn. P. amygdalus Batsch) is one of the most important nut crops, and its kernel is the edible part that has a high nutritional value and is used in the confectionery and cosmetics industries. The present research aimed to identify random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) molecular markers associated with important fruit traits in late-blooming almond genotypes through multiple regression analysis (MRA). The studied genotypes showed significant differences from each other in terms of the measured fruit-related traits. The ISSR primers used produced a total of 125 bands in the studied germplasm, of which 112 showed polymorphic bands. The RAPD primers produced a total of 190 DNA fragments, of which 172 fragments showed polymorphism among genotypes. Some polymorphic fragments of ISSR and RAPD showed significant correlations with the fruit traits measured. Some of these informative markers were associated with more than one trait, which could be caused by the pleiotropic effects of quantitative trait loci related to each other in different traits. For instance, some of the markers showed significant correlations with both nut weight and kernel weight, which indicates a positive correlation between these two traits. Informative markers identified in this study can be used to select suitable parents for population generation for mapping. It is also useful for selecting superior genotypes, especially when information about their genetic basis, such as a linkage map, is not available.

Amino-induced cadmium metal-organic framework based on thiazole ligand as a heterogeneous catalyst for the epoxidation of alkenes.

Selective epoxidation of olefins is of high interest in the chemical industry due to the many applications of epoxides. This study reports on the synthesis of Cd-MOF, [Cd(DPTTZ)(5-AIP)] (IUST-1) (where DPTTZ = 2, 5-di (pyridine-4-yl) thiazolo [5, 4-d] thiazole, 5-AIP = 5-Aminoisophthalic acid), by a reflux method, which can be considered as a fast and simple process. The morphology and structure of the synthesized IUST-1 were determined by using FE-SEM (Field Emission Scanning Electron Microscopy), EDX (Energy Dispersive Analysis of X-ray), Mapping (Elemental Mapping), CHNS (Elemental analysis), XRD (X-Ray Diffraction), FT-IR (Fourier Transform Infrared), and TGA (Thermo Gravimetric Analysis). The epoxidation of cyclooctene was investigated using the activity of catalytic IUST-1. The results showed that in the presence of tert-butyl hydroperoxide and CCl4 in a 1:2 alkene/oxidant ratio, a high epoxide yield (99.8%) was obtained. In addition, IUST-1 can be easily separated by simple filtration and recycled five times successfully with a slight decrease in activity. This compound has some advantages such as high yield, short reaction time, and ease of reuse, which make it a suitable heterogeneous catalyst for the epoxidation of cyclooctene.

Novel Zn metal-organic framework with the thiazole sites for fast and efficient removal of heavy metal ions from water.

Pollution of water by heavy metal ions such as Pb2+ and Hg2+ is considered as an important issue, because of the potential toxic effects these ions impose on environmental ecosystems and human health. A new Zn-based metal-organic framework, [Zn2(DPTTZ) (OBA)2] (IUST-2), was synthesized through a solvothermal method by the reaction of 2, 5-di (4- pyridyl) thiazolo [5, 4-d] thiazole ligand (DPTTZ), the "V-shape" 4,4'-oxybis (benzoic acid) ligand (OBA) and zinc nitrate (Zn(NO3)2·6H2O). This novel MOF has been characterized by several analysis techniques such as fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA), powder x-ray diffraction (PXRD), thermogravimetry analysis (TGA), differential thermal analysis (DTA), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) surface area analysis and single-crystal X-ray diffraction (SXRD). This 3D MOF was tested for removing Pb2+ and Hg2+ ions from water. The factors that were investigated on the elimination of Pb2+ and Hg2+ ions were of pH, adsorption time, and the effect of initial ions concentration. According to the results, this particular Zn-MOF had significant performance in eliminating Pb2+ and Hg2+ ions from water with a removal efficiency of more than 97% and 87% within 3 min, respectively.

Luminescent Cd coordination polymer based on thiazole as a dual-responsive chemosensor for 4-nitroaniline and CrO42- in water.

A novel highly fluorescent cadmium metal-organic framework, [Cd (DPTTZ) (OBA)] (IUST-3), synthesized by using two linkers 2, 5-di (pyridine-4-yl) thiazolo [5, 4-d] thiazole (DPTTZ) and 4, 4'-oxybis (benzoic acid) (OBA) simultaneously, which exhibits a two-dimensional framework. The characteristics of this Cd-MOF were investigated by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, powder X-ray diffraction, and thermogravimetry analysis. The IUST-3 exhibits excellent luminescence property and good stability in water. Luminescent experiments indicate that the IUST-3 has remarkable sensitivity and selectivity for the detection of 4-nitroaniline (4-NA), and CrO42- anion with KSV = 1.03 × 105 M-1 (4-NA) and KSV = 2.93 × 104 M-1 (CrO42-) and low limit of detection 0.52 µM (4-NA) and 1.37 µM (CrO42-). In addition, the possible fluorescence quenching mechanism was explored in this paper.

European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19.

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss.

Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C (p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.

Clinical Utility of Cerebrospinal Fluid Aß42 and Tau Measures in Diagnosing Mild Cognitive Impairment in Early Onset Dementia.

BACKGROUND: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020. OBJECTIVE: To assess amyloid-ß42 (Aß42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance. METHODS: Thirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aß42, total tau, and p-tau measurements. RESULTS: Patients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aß42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aß42 873.44 pg/ml) (p < 0.01 for CSF total and p-tau measures and p < 0.0001 for CSF Aß42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aß42. CONCLUSION: In early onset AD, low levels of CSF Aß42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.

Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

Symbols of Hope on Pediatric Oncology Ward: Children's Perspective Using Photovoice.

Background Hope nurtures confidence and enhances positivity. It is known to be a critical factor in illness, recovery and healing. This study aimed to identify the views of hospitalized children with cancer about the circumstances and factors that create hope for them in the oncology ward. Methods: This qualitative study explored children's experiences using Photovoice, which is an arts-based approach. Twenty children aged 6-12 years diagnosed with various cancers at a Pediatric Hospital in Tehran, Iran, participated in this study. Participants were requested to take photographs of objects, circumstances, or anything that gave them hope or represented a sign of hope in the oncology ward. The photographs were then used to facilitate face-to-face interviews with these children. Data were analyzed using thematic analysis. Results: Data analysis revealed six main themes: emotional connectedness with nursing staff; the playroom as a means to soften the hospital space; the presence of a parent; symbols of recovery; a touch of nature in the hospital setting; and escaping the hospital cage. Discussion: Hopefulness among children can emanate from diverse events and circumstances within the hospital environment. Nurses and physicians need an understanding of children's perspectives to design interventions to improve hopefulness among hospitalized children with cancer.

Altered hippocampal functional connectivity patterns in patients with cognitive impairments following ischaemic stroke: A resting-state fMRI study.

BACKGROUND: Ischemic stroke with cognitive impairment is a considerable risk factor for developing dementia. Identifying imaging markers of cognitive impairment following ischemic stroke will help to develop prevention strategies against post-stroke dementia. METHODS: We investigated the hippocampal functional connectivity (FC) pattern following ischemic stroke, using resting-state fMRI (rs-fMRI). Thirty-three cognitively impaired patients after ischemic stroke and sixteen age-matched controls with no known history of neurological disorder were recruited for the study. No patient had a direct ischaemic insult to hippocampus on the examination of brain imaging. Seven subfields of hippocampus were used as seeds region for FC analyses. RESULTS: Across all hippocampal subfields, FC with the inferior parietal lobule was reduced in stroke patients as compared with healthy controls. This decreased FC included both supramarginal gyrus and angular gyrus. The FC of hippocampal subfields with cerebellum was increased. Importantly, the degree of the altered FC between hippocampal subfields and inferior parietal lobule was associated with their impaired memory function. CONCLUSION: Our results demonstrated that decreased hippocampal-inferior parietal lobule connectivity was associated with cognitive impairment in patients with ischemic stroke. These findings provide novel insights into the role of hippocampus in cognitive impairment following ischemic stroke.

C-Reactive Protein as a Prognostic Indicator in COVID-19 Patients.

While some biomolecules have been explored to identify potential biomarkers for the prognosis of COVID-19 patients, there is no reliable prognostic indicator of the disease progression and severity. We aimed to evaluate the ability of the C-reactive protein (CRP) to predict COVID-19 infection outcome. This retrospective study was conducted on 429 patients diagnosed with COVID-19 between March 30, 2020, and April 30, 2020. The study population was divided into severe (n = 175) and nonsevere cases (n = 254). Data on demographic characteristics, clinical features, and laboratory findings on admission were collected. The proportion of patients with increased CRP levels was significantly higher in severe cases than in nonsevere patients. Analysis of the receiver operating characteristic (ROC) curve found that CRP could be used as an independent factor in predicting the severity of COVID-19. Also, patients with CRP >64.75 mg/L were more likely to have severe complications. In conclusion, CRP serum levels can predict the severity and progression of illness in patients with COVID-19.