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Subclinical hypothyroidism is associated with basal ganglia enlarged perivascular spaces and overall cerebral small vessel disease load

Posted on February 10, 2022 By Clayton No Comments on Subclinical hypothyroidism is associated with basal ganglia enlarged perivascular spaces and overall cerebral small vessel disease load
Background: The association between subclinical hypothyroidism (SCH) and cerebral small vessel disease (CSVD) in the stroke-free population is currently unclear.
Methods: A total of 354 individuals without a history of stroke were enrolled in this study. Demographic data, medical history, vascular risk factors, carotid arteriosclerosis, and the results of laboratory tests were collated. SCH is defined as an elevation in thyroid-stimulating hormone levels, but with normal free thyroxine levels. Magnetic resonance imaging (MRI) was used to assess 4 markers of CSVD, including white matter hyperintensities (WMHs), lacunes, deep microbleeds, and enlarged perivascular spaces (EPVSs).
The overall CSVD load was then ranked using an ordinal scale ranging from 0 to 4. Brain atrophy was measured semi-quantitatively on MRI. A binary logistic regression model was used to explore the association of SCH with each CSVD marker after adjusting for confounding factors. The ordinal regression model was used to explore the association of SCH with CSVD burden and brain atrophy after adjusting for confounding factors.
Results: The mean age of the participants (66.9% males) was 69.4±12.8 years. SCH was observed in 44 (12.4%) participants. MRI findings revealed 13% of cases with lacunes, 6.2% with microbleeds, 50.3% with confluent WMH, and 49.2% with extensive basal ganglia EPVS. Assessment of total CSVD burden showed that 29.1% scored 1, 30.5% scored 2, 6.5% scored 3, and 2.3% scored ≥3. SCH was associated with extensive basal ganglia EPVS Gentaur Whatman Filter  [odds ratio (OR) =2.175; 95% confidence interval (CI): 1.075 to 4.401] and total CSVD load (OR =1.879; 95% CI: 1.028 to 3.438). SCH was not associated with advanced brain atrophy.
Conclusions: SCH is associated with the advanced total burden of CSVD and basal ganglia EPVS in the stroke-free population.

Nanotheranostics: A powerful next-generation solution to tackle hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an epidemic burden and remains highly prevalent worldwide. The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted, complex nature of treatment. Meanwhile, current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC. Hence, alternative approaches are required to improve detection and enhance the efficacy of current treatment options.
Nanotheranostic platforms, which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery, has been considered a potential approach for cancer management in the past few decades. Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field, allowing for more sensitive and specific diagnosis, real-time monitoring of drug delivery, and enhanced treatment efficacies across various malignancies.
The focus of this review is on the applications of nanotheranostics for HCC. The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment. It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general, and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.
Keywords: Future therapy; Hepatic cancer; Hepatocellular carcinoma; Nanoplatform; Nanotheranostic; Personalized medicine.

Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer

LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells.

FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion.

Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.

Futility in Transcatheter Aortic Valve Implantation: A Search for Clarity

Although transcatheter aortic valve implantation (TAVI) has revolutionised the landscape of treatment for aortic stenosis, there exists a cohort of patients where TAVI is deemed futile. Among the pivotal high-risk trials, one-third to half of patients either died or received no symptomatic benefit from the procedure at 1 year.

Futility of TAVI results in the unnecessary exposure of risk for patients and inefficient resource utilisation for healthcare services. Several cardiac and extra-cardiac conditions and frailty increase the risk of mortality despite TAVI. Among the survivors, these comorbidities can inhibit improvements in symptoms and quality of life. However, certain conditions are reversible with TAVI (e.g. functional mitral regurgitation), attenuating the risk and improving outcomes.

Quantification of disease severity, identification of reversible factors and a systematic evaluation of frailty can substantially improve risk stratification and outcomes. This review examines the contribution of pre-existing comorbidities towards futility in TAVI and suggests a systematic approach to guide patient evaluation.

A practical method for storage, preservation and transportation of anuran urine samples using filter paper for hormone analysis

Anurans (frogs and toads) expelled urine when handled and it could provide insights into their physiological status. However, storage, preservation and transportation are often challenging. The study aimed to standardize and validate a field method for short-term storage and preserve of anuran urine samples using Whatman filter papers. To examine the efficacy of storage conditions and type of papers, urinary based enzyme immunoassays were used to measure progesterone and testosterone hormone metabolites.
  • High-Performance Liquid Chromatography was performed and revealed immunoreactive progesterone and testosterone metabolites in the urine samples.
  • Urinary hormone metabolites concentration stored in filter paper at room temperature and control samples stored in -20°C for the same period were similar. 
  • Whatman grade 50 was found to be more suitable for storage of hormones than grade 3 paper for the experiments performed.
  • A cheap and simple storage method for storage of anuran urine in field conditions using filter papers.
  • Anuran urine could be preserved and transported under ambient conditions without significant changes and loss of hormones.
  • This method would facilitate the endocrine monitoring of anurans in remote areas where limited logistics are available.

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