Cirrhosis-downregulated LSECtin can be retrieved by cytokines, shifts the TLR-induced LSECs secretome and correlates with the hepatic Th response.

BACKGROUND AND AIMS: We evaluated tolerogenic C-type lectin LSECtin loss in cirrhosis and its potential regulation by cytokines. METHODS: Liver tissue from patients with cirrhosis and healthy controls, immortalised and generated LSECtin-CRISPR immortalised LSECs, and murine primary LSECs from the CCl4 model were handled. RESULTS: LSECtin expression was reduced in liver tissue from cirrhotic patients, and it decreased from compensated to decompensated disease. Increased phosphorylation of MAPK, Akt and NFkB was observed upon LSECtin stimulation in LSEC murine cell line, showing a pattern of inflammatory and chemotactic cytokines either restrained (IL-10, CCL4) or unrestrained (TNF-α, IL-1ß, IL-6, CCL2). CD44 attenuated whereas LAG-3 increased all substrates phosphorylation in combination with TLR4 and TLR2 ligands except for NFkB. TNF-α, IL-1 ß, IL-6 and CCL2 were restrained by LSECtin crosslinking on TLRs studied. Conversely, IL-10 and CCL4 were upregulated, suggesting a LSECtin-TLRs synergistic effect. Also, LSECtin was significantly induced after IL-13 stimulation or combined with anti-inflammatory cytokines in cirrhotic and immortalised LSECs. Th17 and regulatory T cells were progressively increased in the hepatic tissue from compensated to decompensated patients. A significant inverse correlation was present between gene expression levels of CLEC4G/LSECtin and RORγT and FOXP3 in liver tissues. CONCLUSION: LSECtin restrains TLR proinflammatory secretome induced on LSECs by interfering immune response control, survival and MAPKs signalling pathways. The cytokine-dependent induction of LSECtin and the association between LSECtin loss and Th17 cell subset expansion in the liver, provides a solid background for exploring LSECtin retrieval as a mechanism to reprogram LSEC homeostatic function hampered during cirrhosis.

The Spanish Intergenerational Study: Beliefs, Stereotypes, and Metacognition about Older People and Grandparents to Tackle Ageism.

Ageism can be seen as systematic stereotypes, prejudice, and discrimination of people because of their age. For a long time, society has accepted negative stereotypes as a norm. When referring to older adults, the United Nations Global Report on Ageism warns about a severe impact. The Intergenerational Study for a Healthy Aging, a questionnaire about believes, stereotypes, and knowledge about older people and grandparents, was administered to 326 Spanish biology and medical students. Here we report the results of stereotype analysis through adjective qualification of the youth and older people performed before the survey. Content analysis of two open questions about metacognition at the end of the survey is also presented. The results show that: (1) The questionnaire promoted metacognition; (2) Positive metacognition toward grandparents was higher than for the general old population; (3) Most participants were not conscious about ageism; (4) Gender was a key factor-male students were more ageist than females; (5) The feeling of guilt was higher in the questionnaire about older people; (6) The metacognition exercise elicited thoughts and, in few cases, the need to take action to tackle ageism. In conclusion, both activities promoted active thoughts about older people vs. grandparents and helped participants realize unconscious ageism-specifically toward the older population-serving as an awareness activity that may help tackle ageism.

Comorbid sensorimotor and emotional profiles in the forced swim test immobility and predictive value of a single assay in very old female mice.

The increase of prevalence of mental health problems in the elderly due to the aging of the population becomes an outstanding issue since in most individuals it happens in an already complex multimorbid scenario that may include frailty and age-related medical conditions. Depression, soon the major cause of global disease burden, can be found as an age-related comorbidity and frailty, or as part of neurodegenerative diseases and where females are more vulnerable to it. Thought the multifactorial aetiology and heterogeneous nature of depression render it difficult to be modelled in animals, active behaviours elicited in the Forced Swimming Test (FST) are used to screen antidepressant treatments. However, interpretation of immobility remains controversial. The present work addressed this issue in very-old (21 months) female C57bl/6 × 129 mice, also with the concern that a '6 minutes × 2 days' protocol can result demanding for a very-old animal and confounding factors may also arise. Animals were behaviourally assessed for sensorimotor functions, emotionality and anxiety-like behaviours, novelty seeking, and immobility in a 2-days FST. The predictive value of the first day evidenced that one single assay as sufficient for the assessment of immobility, and that the repeated test did not increase the immobility response. Moreover, sensorimotor tasks, neophobia in the corner test and emotional behaviour in the dark-light box correlated with FST immobility, contributing to the response. The results support the concern of geroscience on the relevance of using aged animals but also aware about taking into account the complexity of their comorbid scenario.

Estimating the epidemiological impact and cost-effectiveness profile of a nonavalent HPV vaccine in Spain.

Human papillomavirus (HPV) is one of the main causes of infection-related cancer. The bivalent vaccine (2vHPV) (16/18) and quadrivalent (6/11/16/18) HPV vaccine (4vHPV) have been included in the Spanish vaccination calendar since 2007. The new nonavalent HPV vaccine (9vHPV), approved in Europe in 2015, includes nine HPV types 6/11/16/18/31/33/45/52/58 and has been available in Spain since May 2017. Our study aims to estimate the epidemiological impact and the cost-effectiveness of a girls-only and a gender-neutral vaccination program with 9vHPV compared to the current vaccination program in Spain. A dynamic transmission model simulating the natural history of HPV infections was calibrated to the Spanish setting and applied to estimate costs and quality-adjusted life years (QALYs) associated with vaccination strategies using a payer perspective and a 100-year time horizon. A girls-only vaccination strategy at age 12 years with 9vHPV was found to be a cost-effective strategy compared with 4vHPV (incremental cost-effectiveness ratio (ICER) of €7,718 per QALY). Compared with girls-only vaccination with 4vHPV, gender-neutral vaccination with 9vHPV was associated with further reductions of up to 28.5% in the incidence of cervical intraepithelial neoplasia (CIN) 2/3 and 17.1% in the incidence of cervical cancer, as well as with a 14.0% reduction in cervical cancer mortality. Furthermore, a gender-neutral vaccination program with 9vHPV could potentially be cost-effective considering some parameters as head and neck protection or discount rates, leading to a reduction in the burden of HPV-related diseases in both sexes in the Spanish population.

Morphological Characterization of the Anterior Palatine Region Using Cone Beam Computed Tomography.

BACKGROUND: Surgery of the anterior maxillary zone has a strong impact upon dental and facial aesthetics and function. PURPOSE: To determine the anatomical characteristics and dimensions of the nasopalatine canal and alveolar bone using cone beam computed tomography (CBCT). MATERIALS AND METHODS: A retrospective, cross-sectional study was made of the nasopalatine canal in 122 randomly selected CBCT scans corresponding to 66 males (44.3%) and 56 females (55.6%). The following measurements were made: maximum length and diameters of the nasal and oral openings of the nasopalatine canal; distance from the crestal margin to the buccal wall (at apical, middle, and coronal level); and angulation of the nasopalatine canal. The anatomical variants were morphologically classified as follows: A (single canal), B (double canal), or C (Y-shaped canal). RESULTS: The anatomy of the nasopalatine canal showed important variability in terms of morphology and dimensions. Type A was observed in 48 patients (39.34%), type B in 10 (8.19%), and type C in 64 (52.45%). The mean diameter of the nasal opening or orifice was 3.02 ± 1.0 mm versus 3.29 ± 1.0 mm in the case of the oral opening. The mean length of the canal was 11.02 ± 2.4 mm. Significant differences were found between males and females, with greater canal dimensions and alveolar bone thickness values anterior to the nasal canal zone among males (p < .05). CONCLUSIONS: Our study shows gender to exert a significant influence upon the anatomical dimensions of the anterior maxilla and incisor canal. Given the anatomical variability characterizing the nasopalatine canal, we recommend CBCT evaluation prior to any type of surgery of the anterior maxillary zone.