Pathological Mineralization: The Potential of Mineralomics

Pathological mineralization has been reported countless times in the literature and is a well-known phenomenon in the medical field for its connections to a wide range of diseases, including cancer, cardiovascular, and neurodegenerative diseases. The minerals involved in calcification, however, have not been directly studied as extensively as the organic components of each of the pathologies. These have been studied in isolation and, for most of them, physicochemical properties are hitherto not fully known. In a parallel development, materials science methods such as electron microscopy, spectroscopy, thermal analysis, and others have been used in biology mainly for the study of hard tissues and biomaterials and have only recently been incorporated in the study of other biological systems. This review connects a range of soft tissue diseases, including breast cancer, age-related macular degeneration, aortic valve stenosis, kidney stone diseases, and Fahr’s syndrome, all of which have been associated with mineralization processes. Furthermore, it describes how physicochemical material characterization methods have been used to provide new information on such pathologies. Here, we focus on diseases that are associated with calcium-composed minerals to discuss how understanding the properties of these minerals can provide new insights on their origins, considering that different conditions and biological features are required for each type of mineral to be formed. We show that mineralomics, or the study of the properties and roles of minerals, can provide information which will help to improve prevention methods against pathological mineral build-up, which in the cases of most of the diseases mentioned in this review, will ultimately lead to new prevention or treatment methods for the diseases. Importantly, this review aims to highlight that chemical composition alone cannot fully support conclusions drawn on the nature of these minerals

Primary Intravascular Synovial Sarcoma of the Femoral Vein in a Male Patient, Case Report

AbstractSynovial Sarcoma (SS) is an aggressive neoplasm commonly affecting deep soft tissues of the extremities. In rare instances SS can arise in large veins of the lower extremities or trunk. We report the first case of intravascular synovial sarcoma (IVSS) occurring in a male patient. A biphasic tumor was diagnosed by histology and immunohistochemistry. Molecular analysis at RNA level confirmed the diagnosis demonstrating the chromosomal translocation t(X;18) (p11.2;q11.2) in the tumor. Although extremely rare, IVSS should be considered in the differential diagnosis of primary intravascular neoplasms and as a potential cause of deep vein thrombosis and thromboembolism

The Use of the Gaps-In-Noise Test as an Index of the Enhanced Left Temporal Cortical Thinning Associated with the Transition between Mild Cognitive Impairment and Alzheimer's Disease

Background: The known link between auditory perception and cognition is often overlooked when testing for cognition. Purpose: To evaluate auditory perception in a group of older adults diagnosed with mild cognitive impairment (MCI). Research Design: A cross-sectional study of auditory perception. Study Sample: Adults with MCI and adults with no documented cognitive issues and matched hearing sensitivity and age. Data collection: Auditory perception was evaluated in both groups, assessing for hearing sensitivity, speech in babble (SinB), and temporal resolution. Results: Mann‐Whitney test revealed significantly poorer scores for SinB and temporal resolution abilities of MCIs versus normal controls for both ears. The right-ear gap detection thresholds on the Gaps-In-Noise (GIN) Test clearly differentiated between the two groups (p < 0.001), with no overlap of values. The left ear results also differentiated the two groups (p < 0.01); however, there was a small degree of overlap ∼8-msec threshold values. With the exception of the left-ear inattentiveness index, which showed a similar distribution between groups, both impulsivity and inattentiveness indexes were higher for the MCIs compared to the control group. Conclusions: The results support central auditory processing evaluation in the elderly population as a promising tool to achieve earlier diagnosis of dementia, while identifying central auditory processing deficits that can contribute to communication deficits in the MCI patient population. A measure of temporal resolution (GIN) may offer an early, albeit indirect, measure reflecting left temporal cortical thinning associated with the transition between MCI and Alzheimer’s disease

SARS-COV-2 Pandemic for Patients with Chronic Obstructive Peripheral Arterial Disease: Impact of Interruption to Access According to Gender in a Single Center Experience

Background: This retrospective study aims to evaluate the impact of interrupted services for peripheral arterial disease (PAD) patients and especially women in a single north-eastern Italian center over a period of 3 months prior to the pandemic, during the first (2020) and the second (2021) wave of contagion in northern Italy. Methods: Patients with PAD at Rutherford stages 3 to 6 that required revascularization between March 2019 and March 2021 were classified into 3 groups, according to the period of treatment: the prepandemic period, the pandemic-20 period, and the pandemic-21 period. Results: Twenty-eight patients were treated in the prepandemic period, 21 in the pandemic-20 period, and 39 in the pandemic-21 period. It was observed that in the both pandemic periods patients presented with more severe stages of limb ischemia, Rutherford 5 and 6 stages. During pandemic-20, patients underwent mostly open surgery, followed by hybrid procedures. No differences were observed between the 3 groups in major amputations, length of hospital stay, type of discharge, limb salvage and mortality. During long-term follow-up, limb salvage appeared to be significantly better in the pandemic-21 group. The gender analysis revealed a significantly reduced female proportion of overall treated patients in 2020 and 2021 compared to the prepandemic period. In the pandemic-20 this difference appears even more evident since treatments on females represented 19% of the total while in the same period of the previous year the male/female percentage was comparable (54% vs. 46%). The women admitted presented higher stages of disease and tended to have a longer hospital stay than men. At 12-month follow-up, limb salvage was similar between the 2 genders but was slightly worse in women. Conclusions: An efficient reorganization of the vascular surgery services during the pandemic period guaranteed the quality and standard of treatment offered in the preceding periods. Among patients suffering from PAD the impact of the pandemic was greater for the female gender. It is therefore important that in addition to a reorganization of hospital services to provide adequate care for patients with ACOP in the pandemic period, greater information and awareness of women

Scanning electron microscopy for blood micro-crystals in aortic stenosis patients.

BACKGROUND: Micro-crystals of calcium phosphate have been detected on the aortic valve of patients with aortic stenosis using scanning electron microscopy. It is not known whether crystalisation is specific to heart valve tissue or a general blood-derived process. METHODS: To this end we modified the method to determine whether calcium phosphate micro-crystals were present in the blood of patients with aortic stenosis. The method was first validated by adding synthetic calcium phosphate hydroxyapatite micro-crystals to healthy volunteer blood samples and determining the lower limit of detection. Then the method was used to examine the blood of 63 patients with echocardiographically confirmed aortic stenosis and 69 unaffected controls undergoing echocardiography for other reasons. Serum calcium and phosphate were measured and the calcium phosphate product compared in cases and controls. RESULTS: In the validation study, synthetic hydroxyapatite micro-crystals were identified down to a lower concentration limit of 0.008mg/mL. In the experimental study no particles were identified in any patient, with or without aortic stenosis, even though serum calcium phosphate was higher in cases compared with controls 2.6mmol/L (2.58-2.77) versus 2.47mmol/L (2.36-2.57), p = 0.005 for the difference. CONCLUSION: The results of our study confirm a positive association between serum calcium phosphate and aortic stenosis, but indicate that the calcium phosphate particles found in valve tissue do not precipitate freely in the blood

Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages

Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. From the Clinical Editor: This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEX n = 138; FEX n = 62; MCO n = 149; FCO n = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331–0.885), FCO (45%, HR: 0.164 95% CI 0.088–0.305), and MCO (44%; HR: 0.157 95% CI 0.096–0.256). A significantly lower rate of hospitalization (p &lt; 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women

Survival and clinical outcomes of diabetic peripheral artery disease patients following a pain-free homebased walking program

Aim: We retrospectively examined the impact on the rate of survival of pain-free home-based exercise in diabetic peripheral artery disease patients compared to patients receiving usual care. Methods: In total, 202 patients at Fontaine's Stage II with diabetes were studied. Half were enrolled in a structured home-based exercise program (E), whereas the other half received walking advice as the active control group (C). Long-term clinical outcomes at five years were gathered from the Emilia-Romagna Health Service Registry, with survival probability selected as the primary outcome. Results: At baseline, the two groups did not differ for any demographic or clinical characteristics. High adherence to the program was recorded in Group E (88% of home-walking sessions executed, with an average distance walked during the program of 174 km). After five years, a survival rate of 90% for Group E and 60% for Group C was observed, with a significantly (P &lt; 0.001) higher mortality risk for Group C [Hazard ratio (HR) = 3.92]. Additionally, among secondary outcomes, Group E showed a significantly (P = 0.048) lower rate of peripheral revascularizations than Group C (15% vs. 24%, respectively; HR = 1.91), all-cause hospitalizations (P = 0.007; 61% vs. 80%, HR = 1.58), and amputations (P = 0.049; 6% vs. 13%, HR = 2.47). In a Cox multivariate-proportional regression model of the entire population, the predictors of survival probability were age (HR = 1.05), Charlson index (HR = 1.24), lower ankle-brachial index (HR = 6.66), and control group (HR = 4.99). Conclusion: A simple sustainable program aimed at improving mobility of diabetic patients with claudication at high cardiovascular risk was associated with better survival and long-term clinical outcomes