Programmed necrosis in the cross talk of cell death and inflammation.

Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity, or immunodeficiency. Programmed necrosis or necroptosis is a form of nonapoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate, mixed lineage kinase domain-like (MLKL). RIPK3 partners with its upstream adaptors RIPK1, TRIF, or DAI to signal for necroptosis in response to death receptor or Toll-like receptor stimulation, pathogen infection, or sterile cell injury. Necroptosis promotes inflammation through leakage of cellular contents from damaged plasma membranes. Intriguingly, many of the signal adaptors of necroptosis have dual functions in innate immune signaling. This unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury.

Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Here, we explore the role of AHR in the pathogenesis of PAH. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. Sprague-Dawley rats treated with the potent endogenous AHR agonist, 6-formylindolo[3,2-b]carbazole, in combination with hypoxia develop severe pulmonary hypertension (PH) with plexiform-like lesions, whereas Sprague-Dawley rats treated with the potent vascular endothelial growth factor receptor 2 inhibitors did not. Ahr-knockout (Ahr-/- ) rats generated using the CRISPR/Cas9 system did not develop PH in the SU5416/hypoxia model. A diet containing Qing-Dai, a Chinese herbal drug, in combination with hypoxia led to development of PH in Ahr+/+ rats, but not in Ahr-/- rats. RNA-seq analysis, chromatin immunoprecipitation (ChIP)-seq analysis, immunohistochemical analysis, and bone marrow transplantation experiments show that activation of several inflammatory signaling pathways was up-regulated in endothelial cells and peripheral blood mononuclear cells, which led to infiltration of CD4+ IL-21+ T cells and MRC1+ macrophages into vascular lesions in an AHR-dependent manner. Taken together, AHR plays crucial roles in the development and progression of PAH, and the AHR-signaling pathway represents a promising therapeutic target for PAH.

Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients.

INTRODUCTION: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD. AIM: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD. METHOD: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period. RESULTS: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002). CONCLUSION: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients. CLINICAL TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

Diasporic Identity in Contemporary Sinophone Literature: The Role of Language and Cultural Elements.

Amidst the contemporary diasporic landscape in Sinophone literature, this research critically examines the nexus of language, culture, and identity. The study aims to analyze literary pieces composed in Sinophone languages across diverse diasporic communities and uncover the impact of language and cultural elements on the articulation and comprehension of diasporic identity. This paper used the following. comparative and typological research, an in-depth analysis of three Sinophonic texts, and contextual analysis. The subject of the study was three texts: The Joy Luck Club (Amy Tan), Balzac and the Little Chinese Seamstress (Dai Sijie), and The Woman Warrior (Maxine Hong Kingston). The results showed that In The Joy Luck Club, language and cultural facets unveil the characters' dual identity struggles due to living abroad, exemplified through code-switching's psychological tension. Balzac and the Little Chinese Seamstress utilizes language and cultural details to underscore the significance of preserving heritage within the diaspora, with literary allusions amplifying this endeavor. In The Woman Warrior, language and cultural elements reflect the heroine's inner conflict as she navigates her dual cultural allegiance. This scholarly revelation deepens comprehension of how these aspects influence identity formation in the diaspora. These findings broaden the understanding of Sinophone diasporic literature, spotlighting shared trends in identity portrayal through language and culture. The research has theoretical value for literary, cultural, and anthropological studies and practical significance, potentially informing educational initiatives on diasporic literature and cultural diversity. This study's outcomes hold relevance for students, researchers, and cultural scholars exploring the role of language and culture in diasporic identity expression.

Enrichment of Zα domains at cytoplasmic stress granules is due to their innate ability to bind to nucleic acids.

Zα domains recognize the left-handed helical Z conformation of double-stranded nucleic acids. They are found in proteins involved in the nucleic acid sensory pathway of the vertebrate innate immune system and host evasion by viral pathogens. Previously, it has been demonstrated that ADAR1 (encoded by ADAR in humans) and DAI (also known as ZBP1) localize to cytoplasmic stress granules (SGs), and this localization is mediated by their Zα domains. To investigate the mechanism, we determined the interactions and localization pattern for the N-terminal region of human DAI (ZαßDAI), which harbours two Zα domains, and for a ZαßDAI mutant deficient in nucleic acid binding. Electrophoretic mobility shift assays demonstrated the ability of ZαßDAI to bind to hyperedited nucleic acids, which are enriched in SGs. Furthermore, using immunofluorescence and immunoprecipitation coupled with mass spectrometry, we identified several interacting partners of the ZαßDAI-RNA complex in vivo under conditions of arsenite-induced stress. These interactions are lost upon loss of nucleic acid-binding ability or upon RNase treatment. Thus, we posit that the mechanism for the translocation of Zα domain-containing proteins to SGs is mainly mediated by the nucleic acid-binding ability of their Zα domains. This article has an associated First Person interview with Bharath Srinivasan, joint first author of the paper.

Female infertility and dietary antioxidant index (DAI); a case-control study.

BACKGROUND: Adequate intake of natural antioxidants may improve female fertility. The aim of this study was to examine the link between female infertility and dietary antioxidant index (DAI). METHODS: This case-control study was conducted on 125 women with recently diagnosis of reduced ovarian reserves (AMH < 1.1) as the case group and 125 women with normal ovarian reserve as the control group in Rasht, Iran. The amount of food intake was assessed using the food frequency questionnaire (FFQ) and the DAI was calculated to estimate the antioxidant capacity of the diet. RESULTS: Regarding dietary intake, the infertile women had a lower intake of potassium (2789.25 ± 777 vs. 2593.68 ± 443 mg/d, P = 0.02), magnesium (204.12 ± 66 vs. 189.73 ± 34 mg/d, P = 0.03), copper (0.93 ± 0.40 vs. 0.82 ± 0.20 mg/d, P < 0.01), vitamin C (133.99 ± 46 vs. 122.62 ± 24 mg/d, P = 0.02), and fiber (14.53 ± 3 vs. 13.44 ± 2 g/d, P < 0.05), and a higher intake of cholesterol (205.61 ± 58 vs. 227.02 ± 46 mg/d, P < 0.01) than the control group (All P < 0.05). The DAI was negatively associated with infertility (OR: 0.94, CI 95%: 0.88-0.97, P = 0.03). The association remained significant after adjustments for age, BMI, the underlying diseases, fertility frequency, IVF failure, and calorie intake. CONCLUSION: Following an antioxidant-rich diet may reduce the risk of infertility. More longitudinal studies are warranted to confirm these results and discover the underlying mechanisms.

THE DETERMINATION OF THE NEED TO PROVIDE ORTHODONTIC ASSISTANCE TO TEENAGERS IN CONDITIONS OF LIMITED RESOURCES.

OBJECTIVE: The aim: To substantiate the need for a combination of interdisciplinary approaches to diagnosis, treatment and correction of dento-maxillofacial anomalies of teenagers based on the analysis of the need for orthodontic treatment using the DAI, IOTN, ICON aesthetic indices. PATIENTS AND METHODS: Materials and methods: Empirical, epidemiological, clinical, analytical-synthetic, sociological, psychological research methods, questionnaires, dental indexeshave been used in various combinations. RESULTS: Results: As a result of a clinical examination of 2,260 teenagers (1,096 boys and 1,124 girls), 1,474 individuals have been bselected for orthodontic treatment with the following degree of complexity: mild - in 25 examined (35.71±4.95%), moderate - in 31 individuals (44.28± 5.48%), heavy - 14 (20.00±3.11%). After an in-depth dental examination and determination of the psychological profile, 70 teenagers have been selected for treatment. CONCLUSION: Conclusions: The effectiveness of the use of dental indices as a screening tool to eliminate the discrepancy between objective medical indicators of the level of need for correction of dento-maxillofacial anomalies and the level of expected results in adolescents has been proven.

[Primary injuries of corpus callosum vessels in craniocerebral injuries]. / Pervichnye povrezhdeniya sosudov mozolistogo tela pri cherepno-mozgovoi travme.

The aim of the scientific work is to establish morphological characteristics of hemorrhages in the corpus callosum as a marker of primary vascular injuries in diffuse axonal injury (DAI) in relation to the goals and objectives of forensic examination. Changes in the structures of corpus callosum were analyzed in 45 corpses of persons with traumatic brain injury who died in hospital from DAI diagnosed according to clinical and instrumental data within 24 hours after the trauma. The changes were characterized by rectic hemorrhages (haemorrhagia per rhexin) in combination with successively developing vascular, tissue, and cellular post-traumatic reactions. These changes were not observed in the control group. The following morphological characteristics of hemorrhages were established: small focal, elongated, clearly contoured hemorrhages of different sizes, up to 4 mm long, up to 0.8 mm wide, unidirectional at an angle from the lower to upper surface of the sagittal corpus callosum section, at least three, grouped in limited areas sized up to 1.5 × 1.0 cm without clear borders. The detected hemorrhages and the course of changes give reason to consider them the result of primary traumatic effects, making them a diagnostic marker of DAI.

The role of dietary antioxidant index and index of nutritional quality in MS onset: finding from an Iranian population-based incident case-control study.

METHODS: This was a large population-based case-control study recruiting 547 incident cases and 1057 population controls between August 2013 and February 2015. DAI and INQ were calculated based on the adolescence dietary intake of the participants. Logistic regression was employed for estimating adjusted odds ratios (OR) and their 95% confidence interval in 2018. RESULTS: Participants with less than median DAI values had two-fold increased risk of MS onset (adjusted OR 2.05, 95% CI: 1.64-2.58, P < 0.001). A significant dose-response pattern for DAI (adjusted OR 1.35, 95% CI: 1.18-1.55, P for trend <0.001) was also detected. In the case of INQ, the strongest decreased risk were detected for vitamin D (OR = 0.09) and Zinc (OR = 0.34), followed by vitamin A (OR = 0.49), Calcium (OR = 0.49) and vitamin B6 (OR = 0.51) (All P-values < 0.05). CONCLUSION: Considering the inherent limitation of case-control designs, an appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of MS risk. Moreover, those with healthier diet assessed by index of nutritional quality were at decreased risk for MS.

Qing-Dai for pediatric ulcerative colitis multicenter survey and systematic review.

BACKGROUND: Pediatric ulcerative colitis (UC) is more challenging to treat than adult UC. Qing-Dai therapy is effective in adults but reports of its efficacy in children are unavailable. We conducted a questionnaire survey on Qing-Dai use among pediatric patients with UC in Japan to determine its efficacy and safety. METHODS: Questionnaires were sent to 31 high-volume centers treating pediatric patients with inflammatory bowel disease. The number of patients using Qing-Dai, short-term and long-term effects, and adverse events were assessed. A systematic review of studies on the efficacy and safety of Qing-Dai usage for UC was also performed. RESULTS: Overall, 29/31 facilities (93.5%) responded, Qing-Dai was used in 107 patients with UC, and 84/107 patients (78.5%) initiated treatment. Within 6 months, 81/101 (80.2%) patients had clinical remission, while 59/92 (64.1%) patients had no relapse and 29/92 (31.5%) experienced only one to two relapses yearly. Eighty-seven percent of the patients underwent regular follow ups for adverse events, among whom one patient was diagnosed with pulmonary arterial hypertension (PAH), five with enteritis, and one with headache. In the systematic review, the clinical remission rate was 50-80%, and PAH was observed in 14 of 1,158 patients (1.2%). CONCLUSIONS: Qing-Dai is highly effective in treating pediatric UC. However, Qing-Dai should be administered with caution as it may cause adverse events such as PAH.

Component Analysis and Anti-Colorectal Cancer Mechanism via AKT/mTOR Signalling Pathway of Sanghuangporus vaninii Extracts.

Sanghuangporus vaninii (Ljub.) L.W. Zhou & Y.C. Dai (SV) is a major cultivar of Sanghuang, which is well known as an excellent anti-tumour drug and reaches the mainstream market in China. Water, 60% ethanol and 95% ethanol were used to extract the drug, and three kinds of polar extracts were obtained separately. Compared with water extracts and 95% ethanol extracts, the 60% ethanol extract had the highest flavonoid content, and its polysaccharide content was greater than that in the 95% ethanol extract and lower than that in the water extract. Its essential components were phenolics whose majority were phenolic acids, flavonoids and phenylpropanoids. This extract has better inhibition effects on the proliferation of SW480 human colon cancer cells, inducing cell apoptosis and blocking G2/M period cells. It can significantly inhibit gene expression and reduce the activation of the AKT/mTOR signalling pathway. The anti-cancer activity of the 60% ethanol extract is satisfactory and may be a result of the combined effects of polysaccharides and flavonoids. The data suggest that the 60% ethanol extract can be used as an adjuvant for chemotherapy and as a potential anti-cancer agent with broad development prospects.

[Morphological markers of pathophysiological changes in the neuronal processes in the acute post-traumatic period of diffuse axonal injury]. / Morfologicheskie markery patofiziologicheskikh izmenenii otrostkov neironov v ostrom posttravmaticheskom periode diffuznogo aksonal'nogo povrezhdeniya mozga.

The purpose of the study was to establish morphological markers of pathophysiological changes in the neuronal processes of in the acute (up to 36 hours) post-traumatic period of diffuse axonal injury (DAI) for the purposes of expert practice. Histological examination of the body of corpus callosum of the corpses of 66 persons dead from DAI and of 25 persons dead from various non-violent and violent causes, excluding head trauma, was performed (control group). Morphological markers of specific pathophysiological changes in the neuronal process were established by light microscopy with the use of immunohistochemical examination in acute period DAI. Uneven contours of the processes suggested displacement of cytoskeletal elements, areas of vacuolization of the cytoplasm of the processes suggested violation of intracellular transport caused by a change of permeability with preserved integrity of the process shell without mechanical separation of the process, uneven thickness (3.9 ± 1.6 µm) of the processes, varicose and cone-shaped thickening of them was a manifestation of focal edema of the neuronal process and compression of the cytoskeleton as a result of ion-enzymatic disorders, uneven coloration, areas of fragmentary compaction of neurofilaments indicated the zones of deformation and compression of the cytoskeleton, zones of granular-lumpy decay and fibrillolysis of neurofilaments indicated destruction of the cytoskeleton. Changes in the neuronal processes are a manifestation of a polyethological general pathological process and are not a differential diagnostic criterion of DAI.

[Clinical presentation and gross appearance of diffuse axonal injury in the early post-injury period]. / Klinicheskaya i makroskopicheskaya kharakteristika diffuznogo aksonal'nogo povrezhdeniya mozga v ostrom posttravmaticheskom periode.

The objective of the study was to investigate and characterize the clinical presentation, and establish macroscopic diagnostic signs of diffuse axonal injury (DAI) in the early (up to 3 days) post-injury period. In DAI, coma develops immediately after head injury and persists for 3 days post-injury until death. The coma is accompanied by dominant primary stem neurological symptoms, hemodynamic and respiratory disturbances and does not progress to a vegetative state. Lifetime computed tomography reveals cerebral hemorrhage in 40.5% of cases. We established the macroscopic signs of head injury in DAI. For the postmortem diagnosis of DAI, a detailed macroscopic appearance of pathognomonic cerebral hemorrhages is given, which are most frequently (67.5%) localized in the corpus callosum (CC), namely in the area from its genu to the middle of the trunk (97%). A rational, improved scheme of excision of CC trunk areas for the histological study is proposed.

[Pattern of mortality and pathomorphology patterns in lungs according to the materials of forensic medical examination of COVID-19 deceased (March-December 2020)]. / Struktura smertnosti i patomorfologicheskaya kharakteristika legkikh po materialam sudebno-meditsinskogo issledovaniya umershikh ot COVID-19 (mart­dekabr' 2020 g.).

The objective was to study the pattern of mortality and pathomorphological changes in lungs according to the forensic medical investigation of the corpses of the persons who died at the age of 37 to 60 years and older from COVID-19 outside healthcare facilities with no symptoms according to the catamnesis data. Eighty-nine autopsy samples taken from patients with COVID-19 confirmed by polymerase chain reaction (PCR) from the Thanatology Department of the Republican Center of Forensic Medicine for March-December 2020 were analyzed. Pathomorphological changes in the lungs corresponded to different phases of diffuse alveolar injury (DAI) development. During the exudative phase, edema, sloughing of the alveolar epithelium, presence of hyaline membranes, and thrombohemorrhagic events were predominant. In the proliferative phase, fibrin and fibrin-like deposits in alveoli, interalveolar septa thickening, excessive growth of conjunctive tissue in the interalveolar septa, pronounced fatty liver dystrophy, severe myocardium edema were observed.

[Methodology for forensic diagnosis of diffuse axonal injury]. / Metodologiya sudebno-meditsinskoi diagnostiki diffuznogo aksonal'nogo povrezhdeniya golovnogo mozga.

An original methodological approach for forensic diagnostics of diffuse axonal injury (DAI) was developed based on the comprehensive study results. The approach is based on the algorithm of expert actions, including utilizing the developed rational methods set to identify pathognomonic morphological features using accessible and effective histological techniques. Also, the approach includes ways of analysis and estimation of these features. The proposed methodological approach aims to provide an objective diagnosis of this type of traumatic brain injury (TBI) and establish the age of its acute post-traumatic period. The known and generally accepted definitions of DAI and TBI are clarified.

Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis.

Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus. Induction of cell death was cell autonomous and required RNA synthesis but not viral DNA replication. Accordingly, ZBP1 directly bound to RNA via its ZBDs. Intact ZBP1-ZBDs were also required for necroptosis triggered by ectopic expression of ZBP1 and caspase blockade, and ZBP1 cross-linked to endogenous RNA These observations show that Z-RNA may constitute a molecular pattern that induces inflammatory cell death upon sensing by ZBP1.

ZBP1/DAI-Dependent Cell Death Pathways in Influenza A Virus Immunity and Pathogenesis.

Influenza A viruses (IAV) are members of the Orthomyxoviridae family of negative-sense RNA viruses. The greatest diversity of IAV strains is found in aquatic birds, but a subset of strains infects other avian as well as mammalian species, including humans. In aquatic birds, infection is largely restricted to the gastrointestinal tract and spread is through feces, while in humans and other mammals, respiratory epithelial cells are the primary sites supporting productive replication and transmission. IAV triggers the death of most cell types in which it replicates, both in culture and in vivo. When well controlled, such cell death is considered an effective host defense mechanism that eliminates infected cells and limits virus spread. Unchecked or inopportune cell death also results in immunopathology. In this review, we discuss the impact of cell death in restricting virus spread, supporting the adaptive immune response and driving pathogenesis in the mammalian respiratory tract. Recent studies have begun to shed light on the signaling pathways underlying IAV-activated cell death. These pathways, initiated by the pathogen sensor protein ZBP1 (also called DAI and DLM1), cause infected cells to undergo apoptosis, necroptosis, and pyroptosis. We outline mechanisms of ZBP1-mediated cell death signaling following IAV infection.

ZBP1: Innate Sensor Regulating Cell Death and Inflammation.

Z-DNA-binding protein 1 (ZBP1), initially reported as an interferon (IFN)-inducible tumor-associated protein, harbors nucleic acid-binding domains for left-handed helix (Z-form) and receptor-interacting protein homotypic interaction motif (RHIM) domains for protein homotypic interactions. Recent studies have identified ZBP1 as an innate sensor of viral infections and a target of viral evasion strategies, regulating cell death, inflammasome activation, and proinflammatory responses. ZBP1 also functions during development and can trigger perinatal lethality when its RHIM-dependent interactions are not restricted. Here we review the history and emergence of ZBP1 as a pathogen sensor and a central regulator of cell death and inflammatory responses. We also discuss the gaps in our knowledge regarding the regulation and functions of ZBP1 and highlight potential avenues for future research.

Diffuse axonal injury predicts neurodegeneration after moderate-severe traumatic brain injury.

Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate-severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (>50% for fractional anisotropy versus <5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials.

The health perceptions, dengue knowledge and control willingness among Dai ethnic minority in Yunnan Province, China.

BACKGROUND: Outbreaks of dengue fever are often found among Dai ethnical communities along China-Myanmar border. The objective of this study was: 1) to investigate residents' health perceptions, knowledge and control willingness to participate in dengue control and 2) to identify factors associated with control willingness among the Dai ethnic community. METHODS: This is a mixed method study of a cross-sectional design, in which qualitative in-depth interviews and quantitative household questionnaire surveys are included. RESULTS: Questionnaire was administered to 261 household heads, and in-depth interview was conducted with 18 key informants. Of them, many participants (70%, 182/259) and 12 key informants (66.7%) from the two rural communities believed that the Lord Buddha would protect the good people. Majority of the participants (81.4%, 206/253) knew that fever was one of dengue fever symptoms and most of them (82.2%, 213/259) indicated that mosquitoes could transmit dengue fever. However, only one third of the participants (30.1%, 78/259) indicated the perceived susceptibility of dengue fever, and only a half of them (50.2%, 130/259) indicated the perceived severity of dengue fever. Multivariate logistic analysis (MLA) indicated that the participants with family wealth index (FWI) 4-5 (OR: 22.9728; 95%CI: 2.4257-217.5688, p = 0.0063) were more likely to turn containers upside down (TCUD) compared to those with FWI 1-3; and the participants in the urban community (OR: 0.0239; 95%CI: 0.0019-0.3032, p = 0.004) were less likely to TCUD compared to those in the two rural communities. Around one third of the participants (36.8%, 96/239) reported that they were willing to seek treatment first for dengue fever from public health facilities. The MLA identified that the participants with the perceived severity of dengue fever (OR: 5.0564; 95%CI: 2.0672-12.3683, p = 0.0004), and with beliefs of sound hygiene helpful to people's health (OR: 11.5671; 95%CI: 2.0505-65.2502, p = 0.0055) were more likely to seek treatment first for dengue fever from the public health facilities. CONCLUSION: The study finds that most of Dai people have sound knowledge. However, health educational interventions should target to promote the perceived susceptibility and the perceived severity of dengue fever among Dai people.