Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components

Mechanical stimulation appears to play a key role in cartilage homeostasis maintenance, but it can also contribute to osteoarthritis (OA) pathogenesis. Accumulating evidence suggests that cartilage loading in the physiological range contributes to tissue integrity maintenance, whereas excessive or reduced loading have catabolic effects. However, how mechanical stimuli can regulate joint homeostasis is still not completely elucidated and few data are available on human cartilage. We aimed at investigating human OA cartilage response to ex vivo loading at physiological intensity. Cartilage explants from ten OA patients were subjected to ex vivo controlled compression, then recovered and used for gene and protein expression analysis of cartilage homeostasis markers. Compressed samples were compared to uncompressed ones in presence or without interleukin 1ß (IL-1ß) or interleukin 4 (IL-4). Cartilage explants compressed in combination with IL-4 treatment showed the best histological scores. Mechanical stimulation was able to significantly modify the expression of collagen type II (collagen 2), aggrecan, SOX9 transcription factor, cartilage oligomeric matrix protein (COMP), collagen degradation marker C2C and vascular endothelial growth factor (VEGF). Conversely, ADAMTS4 metallopeptidase, interleukin 4 receptor alpha (IL4Ra), chondroitin sulfate 846 epitope (CS846), procollagen type 2 C-propeptide (CPII) and glycosaminoglycans (GAG) appeared not modulated. Our data suggest that physiological compression of OA human cartilage modulates the inflammatory milieu by differently affecting the expression of components and homeostasis regulators of the cartilage extracellular matrix

Mechanized recovery of olive pruning residues: ash contamination and harvesting losses

Agricultural residues represent an important source of biomass for energy. Among the available biomass suitable for energy and available in Italy, pruning represents about the 20% of the total. About 1.184 million of hectares are planted with olive trees; the pruning residues coming from these plantations represent a wide source of biomass at National level. The authors tested six commercial pruning harvesters to determine harvesting losses and product contamination when recovering pruning residues. All harvesters used a mechanical pick-up to collect the residues and a shredder to reduce them into chips. Three different pick-up settings were tested and namely: 1 cm above ground level, manufacturer’s specification and 3 cm above ground level. Ash content in the shredded material was taken as a measure of contamination: the uncontaminated branch material collected directly from the trees had a value of 3.5%, whereas in shredded residues varied between 4.5% and over 5.5%, for the shortest and the longest distance between the pick-up and the soil surface, respectively. Harvesting losses were slightly, but significantly, related to pick-up setting, and mainly depended on machine type. Both machines have shown a good quality of the work performed and the results obtained indicates that the work phases could be simplified in order to reduce both the time of use and the harvesting costs

Implicating factors in the increase in cases of central precocious puberty (CPP) during the COVID-19 pandemic: Experience of a tertiary centre of pediatric endocrinology and review of the literature

Sexual development is a complex mechanism activated by the hypothalamic-pituitary-gonadal axis. Over the last one hundred years there has been a decline in the age at puberty onset in industrialised countries. Some Italian studies showed an increase in diagnoses of Central Precocious Puberty (CPP) during the COVID-19 pandemic. It is thus supposed that in this period there was an increased impact of factors that can influence pubertal development. Our retrospective monocentric study aimed to confirm the existence of this phenomenon and analysed possible related factors. We retrospectively evaluated clinical, laboratory, radiological and ultrasound (US) data of 154 girls referred to our Tertiary Centre of Paediatric Endocrinology from January 2019 to April 2021 for different forms of Precocious Puberty. We subdivided the cases into subgroups according to the final diagnosis: CPP, Early Puberty (EP), isolated thelarche and isolated pubarche. The observation period was subdivided into: Period 1, before lockdown (1 January 2019 - 8 March 2020) and Period 2, lockdown and the following months (9 March 2020 - 30 April 2021). Period 2 was further divided into "restrictive lockdown period" (Period 2.1) (March 2020 - 14 June 2020, in which the schools were closed) and "less restrictive lockdown period" (Period 2.2) (15 June 2020 - 30 April 2021). We analysed data regarding the use of electronic devices before and during lockdown in a group of girls with CPP diagnosed in Period 2 and we compared the data with that of a control group. Our data show an increase in the number of new diagnoses of CPP during lockdown and in the following months, compared with the previous period. We also detected a higher use of PCs and smartphones in girls with CPP diagnosed in Period 2, compared with the control group. The percentage of the presence of endometrial rhyme detected during the pelvic ultrasound was higher in girls with CPP in Period 2, compared with the previous period. Based on our data we assume there was an environmental effect on pubertal timing that calls our attention to factors such as food, use of electronic devices and stress. We will need further studies to better understand this data

Seropositivity-Dependent Association between LINE-1 Methylation and Response to Methotrexate Therapy in Early Rheumatoid Arthritis Patients

Background: Methotrexate (MTX) is considered the first choice among disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) treatment. However, response to it varies as approximately 40% of the patients do not respond and would lose the most effective period of treatment time. Therefore, having a predictive biomarker before starting MTX treatment is of utmost importance. Methylation of long interspersed nucleotide element-1 (LINE-1) is generally considered a surrogate marker for global genomic methylation, which has been reported to associate with disease activity after MTX therapy. Methods: We performed a prospective study on 273 naïve early RA (ERA) patients who were treated with MTX, followed up to 12 months, and classified according to their therapy response. The baseline LINE-1 methylation levels in peripheral blood mononuclear cells (PBMC) of cases were assessed by bisulfite pyrosequencing. Results: Baseline LINE-1 methylation level per se turned out not to predict the response to the therapy, nor did age, sex, body mass index, or smoking status. However, if cases were stratified according to positivity to rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) or seronegativity, we observed an opposite association between baseline LINE-1 methylation levels and optimal response to MTX therapy among responders. The best response to MTX therapy was associated with hypermethylated LINE-1 among double-positive ERA cases (p-value: 0.002) and with hypomethylated LINE-1 in seronegative ERA patients (p-value: 0.01). Conclusion: The LINE-1 methylation level in PBMCs of naïve ERA cases associates with the degree of response to MTX therapy in an opposite way depending on the presence of RF and ACPA antibodies. Our results suggest LINE-1 methylation level as a new epigenetic biomarker for predicting the degree of response to MTX in both double-positive and seronegative ERA patients

Post-Acute COVID-19 Joint Pain and New Onset of Rheumatic Musculoskeletal Diseases: A Systematic Review

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases

Polyamine supplementation reduces DNA damage in adipose stem cells cultured in 3-D

According to previous research, natural polyamines exert a role in regulating cell committment and differentiation from stemness during skeletal development. In order to assess whether distinct polyamine patterns are associated with different skeletal cell types, primary cultures of stem cells, chondrocytes or osteoblasts were dedicated for HPLC analysis of intracellular polyamines. Spermine (SPM) and Spermidine (SPD) levels were higher in adipose derived stem cells (ASC) compared to mature skeletal cells, i.e. chondrocytes and osteoblasts, confirming the connection of polyamine content with stemness. To establish whether polyamines can protect ASC against oxidative DNA damage in a 3-D differentiation model, the level of gamma H2AX was measured by western blot, and found to correlate with age and BMI of patients. Addition of either polyamine to ASC was able to hinder DNA damage in the low micromolecular range, with marked reduction of gamma H2AX level at 10 mu M SPM and 5 mu M SPD. Molecular analysis of the mechanisms that might underlie the protective effect of polyamine supplementation evidences a possible involvement of autophagy. Altogether, these results support the idea that polyamines are able to manage both stem cell differentiation and cell oxidative damage, and therefore represent appealing tools for regenerative and cell based applications

Building a rheumatology biobank for reliable basic/translational research and precision medicine

Research biobanks are non-profit structures that collect, manipulate, store, analyze and distribute systematically organized biological samples and data for research and development purposes. Over the recent years, we have established a biobank, the Rheumatology BioBank (RheumaBank) headed by the Medicine and Rheumatology unit of the IRCCS Istituto Ortopedico Rizzoli (IOR) in Bologna, Italy for the purpose of collecting, processing, storing, and distributing biological samples and associated data obtained from patients suffering from inflammatory joint diseases. RheumaBank is a research biobank, and its main objective is to promote large-scale, high-quality basic, translational, and clinical research studies that can help elucidate pathogenetic mechanisms and improve personalization of treatment choice in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritides (SpA)

A Multidisciplinary Approach for the Development of a Supply Chain in Biomass Conversion of Agrifood Waste Mediated by Larvae of Hermetia illucens L.: From Rearing to By-Product Exploitation

Black soldier fly larvae (BSFL) can convert various organic substrates into high added-value biomass. In addition, the residue can be used as a soil conditioner. Several studies have been conducted on a laboratory scale that may not represent what happens on a prototype scale. Using fruit and vegetable waste as a basic substrate, mixing them with agro-industry by-products (called co-substrates), the Hermes project set up a process on medium (2 kg) and large (10 kg) scales with two different feeding regimes (1.25 g/BSFL and 2 g/BSFL). At the mature stage, larval biomass was separated from frass (the by-product of the larval rearing). The production of larval proteins and fats and the use of frass as soil conditioning were evaluated. The lowest feeding regime (1.25 g/BSFL) provided the best waste valorization. The shift towards higher production scales is not completely linear. The addition of co-substrates to fruit and vegetable waste, as they are provided by the large-scale retail trade, can help to standardize a process as part of an insect farm. The frass recovered from the residue of rearing (on the diet or on the agrifood leftovers) was composted and used in field to grow a processing tomato variety. The addition of composted frass assured a slightly lower yield than synthetic fertilizer but there was no statistically significant difference (p > 0.10). This suggests that partial replacement of synthetic fertilizer with composted frass has potential. Overall, the work demonstrated that, using a multidisciplinary approach, the interest and the value in building a supply chain based on bioconversion mediated by Hermetia illucens can be emphasized

The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition

Background: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression.Methods: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions.Results: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations.Discussion: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression