Triggering of Toll-like receptors in the elderly. A pilot study relevant for vaccination

The impaired ability of the elderly to mount an efficient immune response after exposure to microbes or vaccines represents a major challenge in protection against pathogens in ageing. Recently studies have shown that stimulation of Toll-like receptors (TLRs), using stimulatory ligands, can enhance vaccine efficacy by a number of mechanisms, including the activation of innate immune cells and the consequent production of inflammatory cytokines

The importance of the interactions between KIRs and HLA ligands in the development of human autoimmune and viral diseases

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain KIR/HLA combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIR profiles may be detrimental in autoimmune pathogenesis, and specific KIR genes may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. Here we reviewed a growing body of evidence purporting the influence of KIR polymorphism and KIR-HLA interaction in the development of the main human autoimmune and viral diseases

Klotho and vitamin D in multiple sclerosis: an Italian study

Introduction Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both risk and disease progression). Material and methods 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. Results Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l, p = 0.07). Conclusions Our findings did not identify a role of Klotho in the genetic susceptibility to MS

Comparison of a rapid immunochromatographic test with a chemiluminescence immunoassay for detection of anti-SARS-CoV-2 IgM and IgG

Introduction: The 2019 Coronavirus disease (COVID-19) has been characterized as a pandemic, representing a serious global public health emergency. Serological tests have been proposed as reliable tools for detecting Coronavirus SARS-CoV-2 antibodies in infected patients, especially for surveillance or epidemiological purposes. The aim of this study is to evaluate the agreement between the IgM/IgG rapid assays, based on lateral flow immunochromatographic assay, and the fully automated 2019-nCoV IgM and IgG, based on chemiluminescence immunoassay. Materials and methods: SARS-CoV-2 antibodies were measured with the BIOSYNEX COVID-19 BSS IgM/IgG test (BIOSYNEX, Illkirch-Graffenstaden, France) and the MAGLUMI CLIA (IgM and IgG) (SNIBE – Shenzhen New Industries Biomedical Engineering, Shenzhen, China) in 70 serum samples from patients with PCR-confirmed diagnosis. The strength of the agreement of the two methods was calculated by using the Cohen Kappa index. Results: The results showed a good grade of concordance between the two immunoassays with a Cohen’s kappa coefficient of 0.71 (95%CI: 0.54- 0.87) for IgG SARS-CoV-2 antibodies and 0.70 (95%CI: 0.53-0.87) for IgM SARS-CoV-2 antibodies. In addition, the rapid assays BIOSYNEX COVID-19 BSS for detecting SARS-CoV-2 antibodies showed a positive likelihood ratio (LR) of 10.63 (95%CI: 2.79-40.57) for IgG and a LR of 6.79 (95%CI: 2.93- 15.69) for IgM. Conclusion: Our results suggest that the immunochromatographic rapid IgM/IgG test and the chemiluminescence IgM and IgG immunoassay have a good degree of concordance, suggesting that both could be considered as useful tools for epidemiologic surveillance

Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis

Objectives: Monocyte distribution has recently emerged as a promising biomarker of sepsis, especially in acute setting, such as Emergency Department and Intensive Care Unit. This study aimed to evaluate the accuracy of monocyte distribution width (MDW) for early detecting patients with sepsis by performing a systemic review and meta-analysis of published studies. Methods: Relevant publications were identified by a systematic literature search on PubMed and Google Scholar from inception to September 07, 2021. Studies were divided into two groups based on the sepsis criteria applied, namely sepsis-2 or sepsis-3. Results: Ten studies including 9,475 individuals, of whom 1,370 with sepsis (742 according Sepsis-2 and 628 according to Sepsis-3), met the inclusion criteria for our meta-analysis. The pooled sensitivity and specificity were 0.789 and 0.777 for Sepsis-2 criteria, 0.838 and 0.704 for Sepsis-3 criteria. Conclusions: MDW represents a reliable biomarker for sepsis screening

COVID-19 and Alzheimer's Disease

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer's Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to be more prone to developing AD. On the other hand, AD patients could be more susceptible to severe COVID-19. In this review, we sought to provide an overview on the relationship between AD and COVID-19, focusing on the potential role of biomarkers, which could represent precious tool for early identification of COVID-19 patients at high risk of developing AD

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR = 3.36; 95% CI = 1.46-7.74; p = .005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR = 6.47, 95% CI = 2.58-16.26; p < .0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR = 7.06, 95% CI = 0.07-2.19; p = .002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38 ± 28.49 μmol/L) compared to SLE patients HLA-C1 negative (108.37 ± 86.09 μmol/L) (p = .03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients

Nutraceutical effects of table green olives: A pilot study with Nocellara del Belice olives

Background: The aim of this study was to analyse the nutraceutical properties of table green olives Nocellara del Belice, a traditional Mediterranean food. The Mediterranean Diet has as key elements olives and extra virgin olive oil, common to all Mediterranean countries. Olive oil is the main source of fat and can modulate oxidative stress and inflammation, whereas little is known about the role of olives. Moreover, emerging evidences underline the association between gut microbiota and food as the basis of many phenomena that affect health and delay or avoid the onset of some age-related chronic diseases. Methods: In order to show if table green olives have nutraceutical properties and/or probiotic effect, we performed a nutritional intervention, administering to 25 healthy subjects (mean age 38,3), 12 table green olives/day for 30 days. We carried out anthropometric, biochemical, oxidative stress and cytokines analyses at the beginning of the study and at the end. Moreover, we also collected fecal samples to investigate about the possible variation of concentration of Lactobacilli, after the olives consumption. Result: Our results showed a significant variation of one molecule related to oxidative stress, malondialdehyde, confirming that Nocellara del Belice green olives could have an anti-oxidant effect. In addition, the level of interleukin-6 decreased significantly, demonstrating how this food could be able to modulate the inflammatory response. Moreover, it is noteworthy the reduction of fat mass with an increase of muscle mass, suggesting a possible effect on long time assumption of table olives on body mass variation. No statistically significant differences were observed in the amount of Lactobacilli, although a trend towards an increased concentration of them at the end of the intervention could be related to the nutraceutical effects of olives. Conclusion: These preliminary results suggest a possible nutraceutical effect of daily consumption of green table olives Nocellara del Belice. To best of our knowledge, this is the first study performed to assess nutraceutical properties of this food. Of course, it is necessary to verify the data in a larger sample of individuals to confirm their role as nutraceuticals

Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: from Young to Centenarians

People are living longer, but lifespan increase does not coincide with a boost in health-span. Thus, improving the quality of life of older people is a priority. Centenarians reach extreme longevity in a relatively good health status, escaping or delaying fatal or strongly invalidating diseases. Therefore, studying processes involved in longevity is important to explain the biological mechanisms of health and well-being, since knowledge born from this approach can provide valuable information on how to slow aging. We performed the present study in a well characterized very homogeneous sample of 173 people from Western Sicily, to update existing literature on some phenotypic aspects of aging and longevity and to propose a range of values for older people. We classified 5 age groups, from young adults to centenarians, to understand the age and gender-related variations of the different parameters under study. We collected anamnestic data and performed anthropometric, bioimpedance, molecular, haematological, oxidative, and hematochemical tests, adopting a multidimensional analysis approach. An important evidence of the present study is that there are differences related to both age and gender in several biomarkers. Indeed, gender differences seem to be still poorly considered and inadequately investigated in aging as well as in other medical studies. Moreover, we often observed comparable parameters between young and centenarians rather than non-agenarians and centenarians, hypothesizing a sort of slowdown, almost followed by a reversal trend, in the decay of systemic deterioration. The study of centenarians provides important indications on how to slow aging, with benefits for those who are more vulnerable to disease and disability. The identification of the factors that predispose to a long and healthy life is of enormous interest for translational medicine in an aging world

Prognostic Role of CSF β-amyloid 1-42/1-40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1-42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1-40 and Aβ 1-42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a significant correlation of the Aβ 42/40 ratio with age at onset and Mini Mental State Examination (MMSE) scores. No significant correlation of Aβ 1-42 or Aβ 42/40 ratios to the rate of progression of the disease were found. Furthermore, when we stratified patients according to Aβ 1-42 concentration and the Aβ 42/40 ratio, we found that patients with a lower Aβ 42/40 ratio showed a shorter survival. Our results support the hypothesis that Aβ 1-42 could be involved in some pathogenic mechanism of ALS and we suggest the Aβ 42/40 ratio as a potential prognostic biomarker