IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10 in SLE has not been identified. In this review, we focus on the contribution of different CD4+T-cell subsets to IL-10 and autoantibody production in SLE. In particular, we discuss that IL-10 produced by different subsets of adaptive regulatory T-cells, follicular helper T-cells and extra-follicular B-helper T-cells is likely to have different effects on autoreactive B-cell responses. A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future.

Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Human semen quality and environmental and occupational exposure to pollutants: A systematic review.

Background: The aim of the present systematic review was to evaluate the correlation between the exposure to environmental and/or occupational pollutants and possible alteration of semen quality, focalizing the attention on the studies performed using a biomonitoring approach. Methods: The review was conducted from inception to May 11 2023, according to the PRISMA Statement 2020 and using the following databases: Scopus, Pubmed and Web of Science. The protocol was registered on PROSPERO (CRD42023405607). Studies were considered eligible if they reported data about the association between exposure to environmental pollutants and alteration of semen quality using human biomonitoring. The quality assessment was carried out by the use of the Newcastle-Ottawa Quality Assessment Scale. Results: In total, 21 articles were included, conducted in several countries. The main matrices used for biomonitoring were urine and blood and the most sought-after contaminants were bisphenols, phthalates, pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, heavy metals and other inorganic trace elements. The results of the studies demonstrated a significant positive correlation between the increase of the pollutants' levels in the biological matrices examined and some alterations of the semen quality indicators, such as a decrease in motility, concentration and morphology of the spermatozoa. Conclusions: Male fertility can be negatively affected by the exposure to environmental and/or occupational pollutants. Human biomonitoring programs may be considered a useful tool for specific surveillance programs devoted to early highlight subjects who are more exposed to environmental pollutants in order to reduce risk exposure.

Prosthetic rehabilitation of maxillary lateral incisors agenesis using dental mini-implants: a multicenter 10-year follow-up.

OBJECTIVES: Implants are used to replace congenitally missing lateral incisors but often the space across the alveolar crest is too narrow to permit their use. This multicenter study (Dental Clinic of the University of Foggia, Odontostomatology Clinic of the University of L'Aquila) evaluated the efficacy of mini-implants in cases of maxillary lateral incisor agenesis with severe osseous atrophy in 10-year follow-up. MATERIALS AND METHODS: Forty-seven mini-implants have been inserted in 35 patients affected by lateral incisors agenesis (23 single and 12 bilateral ageneses). All patients underwent orthodontic opening of the space of the upper lateral incisors. After the insertion of the implants, the immediate, non-functional loading, positioning of crowns, presence of pain during percussion and mini-implant function, horizontal and vertical movement when a force of 5 N was applied, ridge loss, and plaque index have been evaluated 1 month after loading, 1 year after loading, and then every 5 years in the following 10 years. Little's test was used to evaluate the assumption that data of loss to follow-up implants are missing completely at random (MCAR) and that a complete-case scenario could be adopted. Wilcoxon test was carried out to look statistically significant differences between the various parameters resulting in the complete-case scenario and those assumed for the worst scenario. The software R (v. 3.6.1, 2019) was employed to perform the statistical analysis. RESULTS: The results obtained over 10 years range from 89% of success rate in a worst-case scenario to the 100% using a complete-case analysis with satisfactory values of marginal bone resorption and good conditions of the peri-implant tissue. Ten-year follow-up using complete-case analysis shows survival rates of 100% for implants with no signs of peri-implantitis, stability of the marginal bone levels and soft tissue around the dental implants. CONCLUSIONS: The data collected show very good implant stability, absence of progressive peri-implantitis, and satisfactory aesthetical results in time (no signs of infraocclusion). CLINICAL RELEVANCE: Mini-implants can be considered a valid and stable over time solution in the restorative treatment of maxillary lateral incisors agenesis.

Photobiomodulation with polarized light in the treatment of cutaneous and mucosal ulcerative lesions.

In recent decades, regenerative medicine has achieved an important evolution at both a conceptual level and scientific production, which explains the current and future possibilities of therapy and daily clinical practice. The main aim of regenerative medicine is the complex system of repair/regeneration. The current literature on the subject demonstrates the advantage of visible light therapy for skin injuries and diseases with the photobiomodulation in which light at low energy levels modulates intra- and extra-cellular photoreceptors by molecular and cellular processes that can stimulate both anti-inflammatory mechanisms and cell proliferative response. The irradiation effects are activated soon after exposure. The anti-inflammatory action on some classes of cytokines and cells (e.g. mast cells and macrophages) is completed with the stimulation of the nitric oxide production, which has an anti-inflammatory and vasodilation action, and gives analgesic relief. Our attention focused on photobiomodulator medical device emitting polarized light. 30 patients (19 women and 11 men) were enrolled in the present study. They were treated for chronic lesions using Bioptron® Light Therapy System device. Patients were initially subjected to Bioptron® light for 20 min after cleansing of the lesion. The operating protocol provides 24 sessions: twice per week for 12 weeks. Twenty patients have been studied for symptoms, histological samples and ulcer characteristics. After 2 months, a reduction of 50% of the lesions was recorded in 18 patients (60%), while in the remaining patients a slower healing was observed. The total wound healing was achieved after 3 months in 13 patients (43%). The examined parameters of the symptom were exudation, pain and signs of infection. Results at 1 and 3 months were, Exudation: at 1 month reduction and positive modulation was observed in 16 patients (53%) and in 25 patients at 3 months; Pain: (evaluated with Vas scale), decreased in 21 patients at 1 month (70%) and in 100% of cases at 3 months; Infections: regressed or disappeared in 100% of cases after the first month. Today, it is no longer time for monotherapy applications, especially in regenerative medicine and the adoption of biophysical therapies can play a positive anti-inflammatory and regenerative role enhancing the function of non-invasive therapies.

Cytokine genotype distribution in patients with periodontal disease and rheumatoid arthritis or diabetes mellitus.

The association between oral and systemic health has highlighted the importance of periodontal health and treatment, with the consequence that dental assessment and attention to oral hygiene have assumed an increasingly important part in the clinical management of patients with diabetes mellitus and rheumatoid arthritis. The aim of this work was to assess genotype frequencies in polymorphisms of genes of IL-1α-889 and IL-1ß-511 in a case-controlled study population of patients affected by periodontal disease and rheumatoid arthritis or diabetes mellitus.

Lack of anti-inflammatory and anti-catabolic effects on basal inflamed osteoarthritic chondrocytes or synoviocytes by adipose stem cell-conditioned medium.

OBJECTIVE: To define whether good manufacturing practice (GMP)-clinical grade adipose stem cell (ASC)-derived conditioned medium (CM) is as effective as GMP-ASC in modulating inflammatory and catabolic factors released by both osteoarthritis (OA) chondrocytes or synoviocytes. METHODS: OA chondrocytes and synoviocytes were treated with ASC-CM or co-cultured with ASC. Inflammatory factors (IL6, CXCL1/GROα,CXCL8/IL8, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES) and proteinases, such as metalloproteinase (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS4, ADAMTS5) and their tissue metalloproteinase inhibitors (TIMP1, TIMP3) were evaluated by qRT-PCR or immunoassays. The involvement of prostaglandin E2 (PGE2) was also analyzed. RESULTS: Most ASC-CM ratios tested did not decrease IL6, CCL2/MCP-1, CCL3/MIP1-α, CCL5/RANTES on basal inflamed chondrocytes or synoviocytes in contrast to what we found using ASC in co-culture. CXCL8/IL8 and CXCL1/GROα were not decreased by ASC-CM on synoviocytes but were only partially reduced on chondrocytes. Moreover, ASC-CM was less efficient both on basal inflamed OA chondrocytes and synoviocytes in reducing proteinases, such as MMP13, ADAMTS4, ADAMTS5 and increasing TIMP1 and TIMP3 compared to ASC in co-culture. The different ratios of ASC-CM contain lower amounts of PGE2 which were not sufficient to reduce inflammatory factors. CONCLUSIONS: These data show that ASC-CM has a limited ability to decrease inflammatory and proteinases factors produced by OA chondrocytes or synoviocytes. ASC-CM is not sufficient to recapitulate the beneficial effect demonstrated using ASC in co-culture with inflamed OA chondrocytes and synoviocytes and shows that their use in clinical trials is fundamental to counteract OA progression.

Fusarium spp. is able to grow and invade healthy human nails as a single source of nutrients.

Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.

Management of biofilm control in an elderly patient suffering from rheumatoid arthritis: a case report.

The increase in the average age of the population forces dentists and dental hygienists to deal with clinical scenarios typical of the elderly. In old people deep changes present both in systemic and oral health. These changes affect the anatomical and functional integrity of many tissues, such as the mouth. Impairment of patients' oral hygiene becomes manifested by local infections and promotes the pathogenesis of periodontal diseases. There is also a significant increase in autoimmune diseases, which are defined as disorders of the immune system that result in abnormal immune responses. Among the autoimmune diseases of medical interest we report a case of rheumatoid arthritis (RA) strictly related to periodontal disease.

The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice.

High mobility group 1 (HMG1) protein is an abundant component of all mammalian nuclei, and related proteins exist in all eukaryotes. HMG1 binds linear DNA with moderate affinity and no sequence specificity, but bends the double helix significantly on binding through the minor groove. It binds with high affinity to DNA that is already sharply bent, such as linker DNA at the entry and exit of nucleosomes; thus, it is considered a structural protein of chromatin. HMG1 is also recruited to DNA by interactions with proteins required for basal and regulated transcriptions and V(D)J recombination. Here we generate mice harbouring deleted Hmg1. Hmg1-/- pups are born alive, but die within 24 hours due to hypoglycaemia. Hmg1-deficient mice survive for several days if given glucose parenterally, then waste away with pleiotropic defects (but no alteration in the immune repertoire). Cell lines lacking Hmg1 grow normally, but the activation of gene expression by the glucocorticoid receptor (GR, encoded by the gene Grl1) is impaired. Thus, Hmg1 is not essential for the overall organization of chromatin in the cell nucleus, but is critical for proper transcriptional control by specific transcription factors.

Functional assessment in endometrial and cervical cancer: diffusion and perfusion, two captivating tools for radiologists.

Uterine cervical and endometrial cancers are two major gynecological malignancies, affecting women's health worldwide. Magnetic resonance imaging (MRI) is appropriate for evaluating malignant disease, thanks to the excellent soft tissue contrast and multiplanar imaging ability. Recently, functional MR techniques, namely diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE), have proved to be a precious support not only in cancer diagnosis but also in disease staging, in the therapy planning, in monitoring response to treatment and during long-term recurrence surveillance. In the field of gynecologic oncology, the European Society of Urogenital Radiology (ESUR) recommends DWI and dynamic contrast-enhanced imaging (DCE-MRI) for local staging of endometrial and cervical cancer, but the potential application of functional imaging in all different aspects of patient management seems very promising. The aim of this article is to summarize the existing literature, providing a comprehensive update on the role of functional MRI in endometrial and cervical cancer.

Diagnostic approach to focal liver lesions at cross-sectional imaging: a primer for beginners.

Liver imaging encompasses a broad spectrum of diseases in different clinical backgrounds. The available literature is vast and reported data often lacks standardization. Because of all these issues, the differential diagnosis and the characterization of liver lesions can be challenging for the beginner. The aim of this narrative review is to provide the basics for an algorithm approach to liver lesions on cross-sectional imaging. First, some tips for the optimization of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) protocols will be provided. Liver Imaging Reporting and Data System (LI-RADS, version 2018) working group is proposing the adoption of their standardized lexicon beyond the original target population of LI-RADS (i.e., liver cirrhosis). Thus, the main imaging findings will be defined following the LI-RADS lexicon. Since the contrast study is the most important for lesion characterization, this narrative review separates the lesions into avascular, hypovascular, and hypervascular, with a focus on chronic liver disease (CLD) and hepatocellular carcinoma (HCC).

CT study protocol optimization in acute non-traumatic abdominal settings.

Abdominal acute pain is a manifestation of heterogeneous medical conditions, with difficult clinical-laboratory assessment. Multi-detector CT (MDCT) is the gold standard imaging technique for evaluating adult patients with acute abdominal pain. Due to its fast execution and the high spatial resolution, CT is fundamental in the diagnostic and therapeutic work-up of patients with time-dependent pathology that could require surgical treatment, reducing mortality and morbidity. However, the radiological risk connected to the ionizing radiation use should not be underestimated, especially in young patients. The aim of this study is to identify optimized CT protocols to apply in the management of non-traumatic acute abdomen. In particular, this review is focused on the main emergency settings: acute pancreatitis, small bowel obstruction, acute appendicitis and acute diverticulitis. This survey would not be complete without mentioning Dual-Energy CT (DECT) technique, one of the last frontiers in CT, achieving encouraging results also in acute abdominal conditions.

Non-traumatic non-cardiovascular thoracic emergencies: role of imaging.

Patients presenting to the emergency with thoracic symptoms could have a wide variety of causes, even if the traumatic and vascular causes are excluded. Therefore, the diagnosis is often a challenge for emergency physicians. Anamnesis, physical examination and laboratory testing need to be integrated with imaging to get a rapid diagnosis and to distinguish among the potential causes. This review discusses the role of diagnostic imaging studies in the emergency setting in patients with non-traumatic non-cardiovascular thoracic symptoms. The use of chest x-ray, bedside lung Ultrasound and Computed Tomography in the diagnosis and care of these patients have been reviewed as well as the common findings on imaging.

Technological advances in body CT: a primer for beginners.

Many technological advances have entered the clinical routine of Computed Tomography (CT) imaging. The new CT scanners have specific solutions in gantry design to bear the mechanical solicitations. The X-ray tubes have been improved for faster acquisitions at low radiation exposure, while the innovations in CT detectors provide a better image quality. The optimization of image quality and contrast, and the reduction of radiation dose, cannot be achieved without the implementation of adequate reconstruction software, such as Iterative Reconstructions (IR) and Artificial Intelligence (AI). In recent years, dual-energy (DECT) technology has expanded the indications of CT. In this narrative review, a panoramic overview of the technological novelties in CT imaging will be provided for optimal utilization of CT technology.

Diagnostic performance of LI-RADS in adult patients with rare hepatic tumors.

OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.

Thoracic non-traumatic cardiovascular diseases: current perspective and multi-detectors Computed Tomography protocols optimization in the emergency setting.

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

Effect of low-level laser irradiation on osteoblast proliferation and bone formation.

Applications of laser therapy in biostimulation and healing injured tissues are widely described in medical literature. The present study focuses on the effects of laser irradiation on the growth rate and differentiation of human osteoblast-like cells seeded on titanium or zirconia surfaces. Cells were laser irradiated with low therapeutical doses at different intervals and the effects of irradiation were evaluated at each time-point. After 3 hours lasered cells showed an enhanced mitogen activity compared to non-lasered control cells and a higher alkaline phosphatase activity, marker of bone formation. At the same time, the mRNA of RUNX2 and OSTERIX, two genes involved in osteoblast differentiation, showed a clear decrease in lasered cells. This reached the lowest value 6 to 12 hours after irradiation, after which the transcripts started to increase, indicating that the laser treatment did promote the osteogenic potential of growth-induced cells. These results indicate that Low Level Laser Treatment (LLLT) stimulates osteogenic cell proliferation.

Risk evaluation of relapse into violent crime in offenders with mental disorders in two different rehabilitation programs: a case-control study.

INTRODUCTION: Over the last years, many research groups have been working on evaluating the most appropriate rehabilitation approaches in offenders with mental disorders, taking into account the need to prevent crime reiteration. The HKT-R (Historisch Klinisch Toekomst- Revised), recently validated in Italy, is a comprehensive tool that offers useful indications to healthcare operators on relapse hazard and major risk areas on which intensify rehabilitation treatments. The present study aims to assess the risk of violent crime recidivism in psychiatric patients during different rehabilitative pats. MATERIALS&METHODS: the risk of violent crime recidivism was assessed by using the HKT-R in 34 patients with mental disorders treated in ordinary psychiatric therapeutic rehabilitative units (CRAP - Comunità Terapeutiche Riabilitative Assistenziali Psichiatriche) and in CRAP-D (Comunità Terapeutiche Riabilitative Assistenziali Psichiatriche Dedicate) specialized in crime offenders. RESULTS AND CONCLUSIONS: Results have demonstrated a higher risk of violent behavior in CRAP-D, and a negative correlation between the risk of violent recidivism, global functioning of patients, and length of care program. These data suggest that residential rehabilita-tion programs, by improving personal and social functioning, could negatively impact the risk of violent crime recidivism, especially in patients with severe mental illness.