Role of the amygdala in disrupted integration and effective connectivity of cortico-subcortical networks in apathy

Background Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. Method We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. Results We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. Conclusion These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.</p

Application of the (fr)AGILE scale in the evaluation of multidimensional frailty in elderly inpatients from internal medicine wards: a cross-sectional observational study

BackgroundWith the rapid growth of an aging global population and proportion, the prevalence of frailty is constantly increasing. Therefore, finding a frailty assessment tool suitable for clinical application by physicians has become the primary link in the comprehensive management of frailty in elderly patients. This study used the (fr)AGILE scale to investigate the frailty status of elderly patients from internal medicine wards and identified relevant factors that affect the severity of frailty.MethodIn this study, 408 elderly inpatients in internal medicine departments of Qilu Hospital of Shandong University from May 2021 to August 2022 were enrolled as research subjects, and a cross-sectional observational study was conducted. Researchers evaluated the frailty based on the (fr)AGILE scale score. The general condition, past medical history, physical examination, laboratory examination, nutrition control score, intervention and treatment measures and other elderly patient information was collected. Logistic regression analysis was used to analyze the relevant factors that affect the severity of frailty and hospitalization costs.ResultsAccording to the (fr)AGILE scale score, the elderly patients were divided into groups to determine whether they were frail and the severity of the frailty. Among them, 164 patients were in the prefrailty stage, which accounted for 40.2%. There were 188 cases of mild frailty that accounted for 46.1%, and 56 cases of moderate to severe frailty that accounted for 13.7%. Decreased grip strength, elevated white blood cell levels, and low sodium and potassium are independent risk factors affecting the severity of frailty. As the severity of frailty increases, the proportion of sodium, potassium, albumin supplementation as well as anti-infection gradually increases.ConclusionFrailty is a common elderly syndrome with a high incidence among elderly patients in internal medicine departments. The main manifestations of frailty vary with different severity levels. Inflammation, anemia, and poor nutritional status can lead to an increase in the severity of frailty as well as blood hypercoagulability, myocardial damage, and additional supportive interventions. This ultimately leads to prolonged hospitalization and increased hospitalization costs

Quality of life in rectal cancer patients with permanent colostomy in Xi’an

Purposes: The aim of this study was to observe the quality of life (QOL) in rectal cancer patients with permanent colostomy in different periods after operation. Methods: A 1-,3-,6-month prospective study of QOL in 51 rectal cancer patients with permanent colostomy and 50 ones without permanent colostomy was assessed by using European Organization for Research and Treatment of Cancer (EORTC) QOL-30 and CR38 questionnaires. Results: The variation of QOL in different periods was “v” type. In the 1st postoperative month, these patients had the lowest quality of life scores, accompanied significantly varied functions and severe symptoms. Almost of all indexes of these patients had improved consistently in postoperative periods. The scores of global QOL even better than pre-operative level at 6th months post-operation, but the social function, body image, chemotherapy side effects and financial difficulties had not restored to the baseline level. Patients without permanent colostomy had a better score in most of categories of QOL-30 and CR38. Conclusions: The 1st postoperative month was crucial for patients’ recovery, in which we should pay great attention to these problems which relate to the recovery of rectal cancer patients with permanent colostomy.Keywords: Quality of life, Rectal cancer, Permanent colostomy, EORTC QOL-30 and CR38 questionnairesAfrican Health sciences Vol 14 No. 1 March 201

Expression mapping of GREM1 and functional contribution of its-secreting-cells in the brain using transgenic mouse models

Gremlin 1 (Grem1) is a secreted protein that antagonizes bone morphogenetic proteins (BMPs). While abnormal Grem1 expression has been reported to cause behavioral defects in postpartum mice, the spatial and cellular distribution of GREM1 in the brain and the influence of the Grem1-secreating cells on brain function and behavior remain unclear. To address this, we designed a genetic cassette incorporating a 3 × Flag-TeV-HA-T2A-tdTomato sequence, resulting in the creation of a novel Grem1Tag mouse model, expressing an epitope tag (3 × Flag-TeV-HA-T2A) followed by a fluorescent reporter (tdTomato) under the control of the endogenous Grem1 promoter. This design facilitated precise tracking of the cell origin and distribution of GREM1 in the brain using tdTomato and Flag (or HA) markers, respectively. We confirmed that the Grem1Tag mouse exhibited normal motor, cognitive, and social behaviors at postnatal 60 days (P60), compared with C57BL/6 J controls. Through immunofluorescence staining, we comprehensively mapped the distribution of Grem1-secreting cells across the central nervous system. Pervasive Grem1 expression was observed in the cerebral cortex (Cx), medulla, pons, and cerebellum, with the highest levels in the Cx region. Notably, within the Cx, GREM1 was predominantly secreted by excitatory neurons, particularly those expressing calcium/calmodulin-dependent protein kinase II alpha (Camk2a), while inhibitory neurons (parvalbumin-positive, PV+) and glial cells (oligodendrocytes, astrocytes, and microglia) showed little or no Grem1 expression. To delineate the functional significance of Grem1-secreting cells, a selective ablation at P42 using a diphtheria toxin A (DTA) system resulted in increased anxiety-like behavior and impaired memory in mice. Altogether, our study harnessing the Grem1Tag mouse model reveals the spatial and cellular localization of GREM1 in the mouse brain, shedding light on the involvement of Grem1-secreting cell in modulating brain function and behavior. Our Grem1Tag mouse serves as a valuable tool for further exploring the precise role of Grem1 in brain development and disease

Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development

Exploration of Macro-Micro Biomarkers for Dampness-Heat Syndrome Differentiation in Different Diseases

Increased attention is being paid to traditional Chinese medicine (TCM) as a complementary and alternative medicine to provide an effective approach for personalized diagnosis and clinical treatment. TMC performs treatment based on differentiation of TCM syndrome (ZHENG), which may identify special phenotypes by symptoms and signs of patients even if they are in different diseases. There has, however, been skepticism and criticism because syndrome classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which lacks objectivity and repeatability. In order to transform syndrome classification into mainstream medicine, we introduce a macro-micro approach that combines symptoms, clinical indicators, and metabolites. The present paper explores the macro-micro biomarkers of dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver patients, which could provide the basis for developing a possible population-screening tool for selecting target individuals and creating an evaluation index for personalized treatment

Mycobacteriophages in diagnosis and alternative treatment of mycobacterial infections

Antimicrobial resistance is an increasing threat to human populations. The emergence of multidrug-resistant “superbugs” in mycobacterial infections has further complicated the processes of curing patients, thereby resulting in high morbidity and mortality. Early diagnosis and alternative treatment are important for improving the success and cure rates associated with mycobacterial infections and the use of mycobacteriophages is a potentially good option. Since each bacteriophage has its own host range, mycobacteriophages have the capacity to detect specific mycobacterial isolates. The bacteriolysis properties of mycobacteriophages make them more attractive when it comes to treating infectious diseases. In fact, they have been clinically applied in Eastern Europe for several decades. Therefore, mycobacteriophages can also treat mycobacteria infections. This review explores the potential clinical applications of mycobacteriophages, including phage-based diagnosis and phage therapy in mycobacterial infections. Furthermore, this review summarizes the current difficulties in phage therapy, providing insights into new treatment strategies against drug-resistant mycobacteria

Grey relational analysis model with cross-sequences and its application in evaluating air quality index

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.It is important to detect the internal operating regularity in system developing with poor information. To identify the real relationship among multi factors, we propose a grey relational analysis (GRA) method inspired by the characteristics of sequences variation. The proposed model considers the changes of fluctuating sequences like cross-sequences both in domain time and between time intervals. To obtain the quantitative change about sequences, relative angle change is employed to determine the variation in each interval, and the relative angle oscillation change is utilized for measuring variations between intervals. To find the optimal time lag or time intervals, the corresponding cycles are extracted by time-delay models. The reliability of the proposed models will be verified through cases in identifying crucial factors for air quality, and the final detection will then be made. To compare with existing representative GRA models clearly, the relation between two fluctuating sequences shaped in cross-sequences is examined by the proposed model. The empirical results show that the relation degree between pollutants and air quality is reasonable. The compared experiment shows that the GRA for cross-sequences can effectively identify the relationship among fluctuating sequences and the impact of time-delay is small for the proposed model with similar shapes

ZHENG-Omics Application in ZHENG Classification and Treatment: Chinese Personalized Medicine

With the hope to provide an effective approach for personalized diagnosis and treatment clinically, traditional chinese medicine (TCM) is being paid increasing attention as a complementary and alternative medicine. It performs treatment based on ZHENG (TCM syndrome) classification, which could be identified clinical special phenotypes by symptoms and signs of patients even if they have a different disease. However, it caused controversy because ZHENG classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which lacks objectivity and repeatability. Although researchers and scientists of TCM have done some work with a lot of beneficial methods, the results could not reach satisfactory with the shortcomings of generalizing the entire state of the body or ignoring the patients' feelings. By total summary, mining, and integration of existing researches, the present paper attempts to introduce a novel macro-microconcept of ZHENG-omics, with the prospect of bright future in providing an objective and repeatable approach for Chinese personalized medicine in an effective way. In this paper, we give the brief introduction and preliminary validation, and discuss strategies and system-oriented technologies for achieving this goal