Label‐free stimulated Raman scattering imaging reveals silicone breast implant material in tissue

Millions of women worldwide have silicone breast implants. It has been reported that implant failure occurs in approximately a tenth of patients within 10 years, and the consequences of dissemination of silicone debris are poorly understood. Currently, silicone detection in histopathological slides is based on morphological features as no specific immunohistochemical technique is available. Here, we show the feasibility and sensitivity of stimulated Raman scattering (SRS) imaging to specifically detect silicone material in stained histopathological slides, without additional sample treatment. Histology slides of four periprosthetic capsules from different implant types were obtained after explantation, as well as an enlarged axillary lymph node from a patient with a ruptured implant. SRS images coregistered with bright‐field images revealed the distribution and quantity of silicone material in the tissue. Fast and high‐resolution imaging of histology slides with molecular specificity using SRS provides an opportunity to investigate the role of silicone debris in the pathophysiology of implant‐linked diseases.     

Effects of alpha-lipoic acid on high fructose induced hepatic pathology

Little is known about the pathogenesis of high fructose corn syrup (HFCS) induced hepatic toxicity. We investigated hepatic lesions induced by chronic HFCS consumption and the protective effects of alpha-lipoic acid (ALA) on liver pathology. We used 24 rats allocated randomly into three groups of eight. The HFCS group was given in drinking water for 10 weeks. The ALA + HFCS group was given the same dose of HFCS and ALA also was administered during the last 6 weeks of the experiment. The control group was untreated. The rats were euthanized at the end of 10 weeks and 24 h after the last ALA administration. A significant increase was observed in the serum aspartate aminotransferase (AST) level of the HFCS group compared to controls. Tissue malondialdehyde (MDA) levels also increased significantly and catalase (CAT) activity decreased significantly in the HFCS group. Caspase-3 expression increased significantly in the HFCS group compared to controls. In the ALA treated group, the levels of MDA, CAT and caspase-3 returned to near control levels. HFCS caused hepatic toxicity by increasing oxidative stress and apoptosis. ALA administration ameliorated the pathological changes.     

Extra virgin olive oil improves synaptic activity,short‐term plasticity,memory, and neuropathology in a tauopathy model

In recent years, increasing evidence has accumulated supporting the health benefits of extra virgin olive oil (EVOO). Previous studies showed that EVOO supplementation improves Alzheimer's disease (AD)‐like amyloidotic phenotype of transgenic mice. However, while much attention has been focused on EVOO‐mediated modulation of Aβ processing, its direct influence on tau metabolism in vivo and synaptic function is still poorly characterized. In this study, we investigated the effect of chronic supplementation of EVOO on the phenotype of a relevant mouse model of tauopathy, human transgenic tau mice (hTau). Starting at 6 months of age, hTau mice were fed chow diet supplemented with EVOO or vehicle for additional 6 months, and then the effect on their phenotype was assessed. At the end of the treatment, compared with control mice receiving EVOO displayed improved memory and cognition which was associated with increased basal synaptic activity and short‐term plasticity. This effect was accompanied by an upregulation of complexin 1, a key presynaptic protein. Moreover, EVOO treatment resulted in a significant reduction of tau oligomers and phosphorylated tau at specific epitopes. Our findings demonstrate that EVOO directly improves synaptic activity, short‐term plasticity, and memory while decreasing tau neuropathology in the hTau mice. These results strengthen the healthy benefits of EVOO and further support the therapeutic potential of this natural product not only for AD but also for primary tauopathies.     

Quantifying Health Across Populations

In this article, I argue that as a theoretical matter, a population's health‐level is best quantified via averagism. Averagism asserts that the health of a population is the average of members’ health‐levels. This model is better because it does not fall prey to a number of objections, including the repugnant conclusion, and because it is not arbitrary. I also argue that as a practical matter, population health‐levels are best quantified via totalism. Totalism asserts that the health of a population is the sum of members’ health‐levels. Totalism is better here because it fits better with cost‐benefit analysis and such an analysis is the best practical way to value healthcare outcomes. The two results are compatible because the theoretical and practical need not always align, whether in general or in the context of population health.     

Mitochondria: Participation to infertility as source of energy and cause of senescence

Mitochondria is a powerhouse organelle involved in ATP synthesis, calcium signaling, reactive oxygen species (ROS) by oxidative stress production, cell cycle arrest via apoptosis and sex steroid hormones biosynthesis. Improvement of sperm parameters such as motility, capacitation, acrosome reaction, and oocyte interaction, involve regulation of ROS levels by the mitochondria. In human, the relation between the quantitative level of mitochondrial DNA (mtDNA), oocyte cytoplasm maturation and fertilization potential, is not clear. It has been hypothesized that oocytes without sufficient wild type mtDNA and therefore able to generate ATP, would not normally be ovulated. This is reflected in the low numbers of mtDNA observed in degenerate oocytes obtained through super ovulation protocols during assisted reproductive technology programs. Different theories place mitochondria in a central role of oxidative damage to cells and tissues related to infertility declining and aging. Mitochondria-dependent apoptosis seems to be responsible for the pre and post-natal decline in germ cells, embryo development, implantation failure, and miscarriages.     

Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder whose exact causative mechanisms are still under intense investigation. Several lines of evidence suggest that the anatomical and temporal propagation of pathological protein species along the neural axis could be among the main driving mechanisms for the fast and irreversible progression of ALS pathology. Many ALS‐associated proteins form intracellular aggregates as a result of their intrinsic prion‐like properties and/or following impairment of the protein quality control systems. During the disease course, these mutated proteins and aberrant peptides are released in the extracellular milieu as soluble or aggregated forms through a variety of mechanisms. Internalization by recipient cells may seed further aggregation and amplify existing proteostatic imbalances, thus triggering a vicious cycle that propagates pathology in vulnerable cells, such as motor neurons and other susceptible neuronal subtypes. Here, we provide an in‐depth review of ALS pathology with a particular focus on the disease mechanisms of seeding and transmission of the most common ALS‐associated proteins, including SOD1, FUS, TDP‐43, and C9orf72‐linked dipeptide repeats. For each of these proteins, we report historical, biochemical, and pathological evidence of their behaviors in ALS. We further discuss the possibility to harness pathological proteins as biomarkers and reflect on the implications of these findings for future research.     

Relevance of the College of American Pathologists guideline for validating whole slide imaging for diagnostic purposes to cytopathology

Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guideline includes three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been beyond the scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology. A systematic search was carried out in PubMed-MEDLINE and Embase databases up to November 2021 to identify all publications regarding validation of WSI in cytology. Each article was reviewed to determine if SRs and/or GPSs recommended by the CAP guideline were adequately satisfied. Of 3963 retrieved articles, 25 were included. Only 4/25 studies (16%) satisfied all three SRs, with only one publication (1/25, 4%) fulfilling all three SRs and nine GPSs. Lack of a suitable validation dataset was the main missing SR (16/25, 64%) and less than a third of the studies reported intra-observer variability data (7/25, 28%). Whilst the CAP guideline for WSI validation in clinical practice helped the widespread adoption of digital pathology, more evidence is required to routinely employ WSI for diagnostic purposes in cytopathology practice. More dedicated validation studies satisfying all SRs and/or GPSs recommended by the CAP are needed to help expedite the use of WSI for primary diagnosis in cytopathology.     

Laser Capture Microdissection in the Tissue Biorepository

An important need of many cancer research projects is the availability of high-quality, appropriately selected tissue. Tissue biorepositories are organized to collect, process, store, and distribute samples of tumor and normal tissue for further use in fundamental and translational cancer research. This, in turn, provides investigators with an invaluable resource of appropriately examined and characterized tissue specimens and linked patient information. Human tissues, in particular, tumor tissues, are complex structures composed of heterogeneous mixtures of morphologically and functionally distinct cell types. It is essential to analyze specific cell types to identify and define accurately the biologically important processes in pathologic lesions. Laser capture microdissection (LCM) is state-of-the-art technology that provides the scientific community with a rapid and reliable method to isolate a homogeneous population of cells from heterogeneous tissue specimens, thus providing investigators with the ability to analyze DNA, RNA, and protein accurately from pure populations of cells. This is particularly well-suited for tumor cell isolation, which can be captured from complex tissue samples. The combination of LCM and a tissue biorepository offers a comprehensive means by which researchers can use valuable human biospecimens and cutting-edge technology to facilitate basic, translational, and clinical research. This review provides an overview of LCM technology with an emphasis on the applications of LCM in the setting of a tissue biorepository, based on the author''s extensive experience in LCM procedures acquired at Fox Chase Cancer Center and Hollings Cancer Center.     

Wuchereria bancrofti: Diminished platelet activation in filarial patients

Blood platelets are the innate immune elements that have not been investigated in human filarial infections. Platelet activation status in the endemic normals (EN), microfilaria positive individuals (MF) and patients with chronic pathology (CP) was evaluated in whole blood, under unstimulated as well as antigen exposed (BmA, E. coli) conditions for PAC-1 expression by Flow cytometry. A diminished PAC-1 expression was observed in MF compared to CP and EN spontaneously as well as upon antigen exposure. Besides this, PAC-1 expression within the groups did not exhibit any significant difference under all the experimental conditions. However in CP patients, E. coli antigen exposure resulted in a significantly reduced PAC-1 expression compared to the spontaneous expression levels. NO release in platelet culture supernatants from EN was inversely proportional to platelet aggregation. Collagen stimulated platelets from EN, exposed to sera and immune complexes from CP and MF patients resulted in elevated Nitric Oxide (NO) release, compared to those exposed to autologous sera and fetal calf serum. In addition, under similar conditions, collagen stimulated platelets from EN, exposed to filarial antigen (BmA) exhibited increased NO compared to the E. coli antigen exposed ones and light microscopic observations of cultured platelets supported the above findings. Thus it appears from the results of the present study that filarial antigen may play a role in the loss of platelet aggregation, leading to platelet inactivation.     

Arthritis of the spondyloarthropathy variety in Callithrix jacchus

Sixty skeletons of Callithrix jacchus were examined to identify spondyloarthropathy. Erosive disease in Callithrix was confirmed as spondyloarthropathy on the basis of diagnostic sacroiliac erosions, syndesmophyte formation, and the nature and distribution of the peripheral joint erosions.