METHOD: This study was approved by the institutional Ethics Committees. Postmortem nasal mucosa and brain tissues from patients with AD (n = 10) and normal subjects (n = 10) were collected with patient consent at the Fukushimura Brain Bank. Nasal and brain tissue homogenates were added to HEK293 cells expressing tau 3-repeat domain with the L266V and V337M mutations (3RD∗VM) or 4-repeat domain with the P301L and V337M mutations (4RD∗LM), which was fused with GFP at the C-terminus.
RESULT: GFP fluorescence was detected uniformly within the cell bodies of HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. There were no changes in the fluorescence after the additions of the brain homogenates from normal subjects. In contrast, a large number of fluorescent puncta was detected both in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP at 4 days after the additions of the brain homogenates from patients with AD. Furthermore, the nasal tissue homogenates from patients with AD also induce the formation of fluorescent aggregates in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. Quantitative analysis revealed that the nasal tissue homogenates from AD patients significantly induced the aggregate formation, compared with normal subjects.
CONCLUSION: These results suggest that the nasal tissues from AD patients contain tau seeds with prion activity, similar to the brain. A cellular bioassay using nasal tissues would be great potential as an AD biomarker because of the usefulness of nasal tissue biopsy, and would provide an important contribution to the development of ex vivo diagnosis method for AD using the nasal extracts.
CASE PRESENTATION: An elderly lady with subacute onset and worsening behavioural changes of three months' duration was referred for exclusion of organic brain disease. The neurological and respiratory examination, chest X-ray, electroencephalogram (EEG), and MRI of the brain were normal. She, however, had elevated C-reactive protein, ESR, and raised CSF opening pressure on lumbar puncture. The CSF cell counts, biochemistry, and cultures were within normal limits. Unable to detect a neurological cause for her illness, she was advised to consult a psychiatrist. Two months later she reported to us again, this time essentially for back pain. Investigations for the back pain (including CT spine) revealed a T12 compression fracture with irregularity of the left T12 pedicle and a para-spinal fluid collection. Pus drained from the collection showed mycobacterium tuberculosis bacteria on staining with ZN stain. The CT scan thorax also showed left lower lobe consolidation and a pleural effusion. Contrast CT scan brain revealed subtle meningeal enhancement at the right parietal region. With standard treatment with a four-drug anti-TB regimen (along with a short course of dexamethasone), she improved well. This case report indicates that the initial clinical presentation of TB in general, as well as DTB, can be misleading, resulting in delay in diagnosis and in initiating treatment.
CASE DESCRIPTION: We present a case of tigecycline-induced acute pancreatitis in a 78-year-old man with complex medical conditions, including type 2 diabetes mellitus, chronic renal insufficiency, and triple vessel disease. The patient was initially treated with tigecycline for bilateral dry gangrene of his toes. Six days after initiation of the tigecycline treatment, the patient developed symptoms of acute pancreatitis with electrocardiogram changes. Magnetic resonance imaging confirmed the diagnosis of acute pancreatitis. Tigecycline was stopped promptly, and supportive treatment was initiated. The patient recovered from the acute pancreatitis and was discharged home. He later passed away at home due to his underlying cardiac disease.
CONCLUSIONS: This case highlights the potential complications of tigecycline therapy, particularly in patients with significant comorbidities.
LEARNING POINTS: Elderly patients with complex medical issues, such as diabetes mellitus type 2, chronic renal insufficiency, and cardiovascular disease, are at higher risk for adverse drug reactions. Recognizing these risk factors is important for management.Addressing the use of magnetic resonance imaging for diagnosing acute pancreatitis in this specific patient due to their already compromised kidneys highlights the need for a tailored approach. Most commonly, angiographic transformers or computed tomography scan are used for high-risk patients.The symptoms of acute pancreatitis and the presence of cardiac diseases cause problems in managing patients. Changes on the electrocardiogram may suggest cardiac overload; as a result, constant follow-up is necessary for patients suffering from underlying cardiac conditions.
DESIGN: This study used an interpretive descriptive qualitative design, employing semistructured purposive sampling for focus group discussions. Thematic analysis was conducted on the transcribed interviews and field notes, facilitated by NVivo 12.0 Plus software.
SETTING: Community settings in Zhengzhou City, Henan Province.
PARTICIPANTS: Middle-aged adults (aged 45-59) were identified as at risk of stroke due to the presence of one or more modifiable risk factors.
RESULT: A total of seven focus group discussions were audio recorded. Four main themes emerged, which were: (1) cognitive understanding of a healthy diet; (2) dietary practices; (3) knowledge acquisition and (4) barriers to dietary adherence.
CONCLUSIONS: The middle-aged adults at risk of stroke were generally aware of the risk and attempted to practise healthy eating. The existing educational programmes on following a healthy diet in the prevention of disease need to be made more comprehensible, accessible and equitable, especially for those from socioeconomically disadvantaged communities.
METHODOLOGY: The cross-sectional study retrospectively reviewed certified RTA fatalities from 2018 to 2021, individually counting fatalities in accidents and excluding cases with incomplete death profiles. Data were collected from all Forensic Departments in the government hospitals in Perak. RTA fatalities were confirmed by medical officers/physicians following established procedures during routine procedures. A total of 2517 fatal accident and victim profiles were transcribed into data collection form after reviewing death registration records and post-mortem reports. Inferential analyses were used for comparison between pre- and during COVID-19 pandemic. The standard expected YLL was calculated by comparing the age of death to the external standard life expectancy curve taking into consideration of age and gender in Malaysia.
RESULTS: This study included 2207 (87.7%) of the RTA fatalities in Perak State. The analysis revealed a decreasing trend in RTA deaths from 2018 to 2021, with a remarkable Annual Percent Change (APC) of -25.1% in 2020 compared to the pre-pandemic year in 2019 and remained stable with lower APC in 2021. Comparison between pre-pandemic (2018-2019) and pandemic years (2020-2021) revealed a difference in the fatality distribution with a median age rise during the pandemic (37.7 (IQR: 22.96, 58.08) vs. 41.0 (IQR: 25.08, 61.00), p = 0.002). Vehicle profiles remained consistent, yet changes were observed in the involvement of various road users, where more motorcycle riders and pedestrian were killed during pandemic (p = 0.049). During pandemic, there was a decline in vehicle collisions, but slight increase of the non-collision accidents and incidents involving pedestrians/animals (p = 0.015). A shift in accident from noon till midnight were also notable during the pandemic (p = 0.028). YLL revealed differences by age and gender, indicating a higher YLL for females aged 30-34 during the pandemic.
CONCLUSION: The decline in RTA fatalities during COVID-19 pandemic underscores the influence of pandemic-induced restrictions and reduced traffic. However, demographic shifts, increased accident severity due to risky behaviors and gender-specific impacts on YLL, stress the necessity for improved safety interventions amidst evolving dynamics.
METHOD: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance.
RESULTS: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC.
CONCLUSIONS: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFβ, Hedgehog axis.
METHODS: 160 eyes of 160 healthy children (74 boys, 86 girls) aged 6-18 years (mean: 11.60 ± 3.28 years) were evaluated in this cross-sectional study. The peripapillary retinal nerve fibre layer (pRNFL) and macular thickness were determined for the 1st, 5th, 95th, and 99th percentile points. Cohen's κ value and specific agreement between pediatric data and adult reference database were estimated. The correlation between retinal thickness with age and SE was also determined.
RESULTS: The mean thickness for the total RNFL, average macular, and central macula were 112.05±8.65 μm, 280.24±12.46 μm, and 220.55±17.53 μm, respectively. The overall agreement between the classification of the adult database and pediatric data for pRNFL was ≥90%, with discrepancies in 46 out of 150 eyes (30.67%); for macula, it was above 72%, with discrepancies in 93 out of 153 eyes (60.78%); and for ganglion cell complex and ganglion cell + inner plexiform layer (GCIPL) the agreement was above 84% and 85%, respectively. A significant level of agreement between pediatric data and adult reference data was achieved for temporal RNFL (κ = 0.65), macular perifoveal superior (κ = 0.67), and inferior (κ = 0.63) and inferior GCIPL (κ = 0.67). The correlations between age and retinal thickness were not significant (all p>0.05). Most retinal thickness parameters were positively associated with SE (Pearson's coefficient, r = 0.26 to 0.49, all p<0.05).
CONCLUSIONS: The overall agreement for pRNFL and macular thickness measurements in children with the adult reference database was between 72% and 90%. Children's retinal thickness was not significantly correlated with age but was positively associated with spherical equivalent.
METHODS: A stratified random sample of 679 female Chinese university students (age, mean ± SD = 19.792 ± 1.007) participated in the study. The surveys comprised the Theory of Reasoned Action Questionnaire (TRA-Q) and the Body Shape Questionnaire (BS-Q) to assess their body shape concerns and behavioral intentions regarding eating disorders. Structural equation modeling was used to test the extended TRA model, with body shape as an additional predictor and BMI as a moderator.
RESULTS: Body shape positively affected attitudes (β = 0.444, p