The Iron Man of the Renaissance: the contribution of Girolamo Fabrizi d'Acquapendente.

PURPOSE: To highlight the most relevant contributions of the Italian Renaissance surgeon Girolamo Fabrizi d'Acquapendente in the field of orthopaedics and traumatology. METHODS: An extensive research on the life and achievements of Girolamo Fabrizi was conducted on University Libraries as well as on electronic databases like PubMed. RESULTS: Girolamo Fabrizi d'Acquapendente is known for his embryology and physiology studies, particularly on sensory organs and blood circulation. He founded the world's first permanent anatomical theater established at the University of Padua and inaugurated in 1595. His most notable publications include surgical and definitely orthopedics works such as "De fracturis" (On fractures) and "De luxationibus" (On joint displacement). He outlined some principles of treatment that are still valid nowadays such as anatomical reduction and stabilization of the fracture, that were applied using the equipment available at that time. He described and illustrated maneuvers and instruments, such as pulleys, winches, splint, and bandages. He further depicted the famous "Oplomochlion" ("the armored man"), which is actually a collection of all of the braces used at the time to correct congenital and post-traumatic deformities. CONCLUSION: Bracing and prosthetic replacements have accompanied medical history throughout the centuries, from Ancient Egypt to the present, but it was the ingenuity of Renaissance surgeons that pushed biomedical technology to new heights: Girolamo Fabrizi d'Acquapendente was one of the most illustrious contributors to these great achievements.

Search for Invisible Decays of a Dark Photon Produced in e

We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data collected with the BABAR detector at the PEP-II B-Factory. We look for events with a single high-energy photon and a large missing momentum and energy, consistent with production of a spin-1 particle A^{'} through the process e^{+}e^{-}→γA^{'}; A^{'}→invisible. Such particles, referred to as "dark photons," are motivated by theories applying a U(1) gauge symmetry to dark matter. We find no evidence for such processes and set 90% confidence level upper limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV. In particular, our limits exclude the values of the A^{'} coupling suggested by the dark-photon interpretation of the muon (g-2)_{µ} anomaly, as well as a broad range of parameters for the dark-sector models.

Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on sensitisation pattern to molecular allergens in children with allergic rhinoconjunctivitis.

BACKGROUND: The diagnostic and therapeutic approach to grass pollen allergy is now possible by detecting specific IgE (sIgE) to its allergenic components. AIM: To evaluate the correlation between the sensitisation to different molecular Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. METHODS: The pilot study included 36 patients affected by allergic rhinoconjunctivitis, all treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4, 5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS) and the Average Combined Score (ACS) were evaluated before and after one year of immunotherapy. RESULTS: Three different groups of sensitisation were defined based on the range of IgE reactivity to Phleum pratense allergens at baseline: group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5 allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79±0.18 in group I; 1.81±0.23 in group II; and 1.95±0.34 in group III. At T1 ACS was 0.85±0.55 in group I; 1.01±0.31 in group II; and 1.44±0.39 in group III. At T1 there was a significant improvement of ARTSS and ACS for group I (p=0.001). CONCLUSIONS: Sublingual immunotherapy with a grass pollen is efficacious irrespective of the patients' baseline sensitisation to either single or multiple grass pollen molecular allergens. We found that patients with few sensitisations have a greater improvement in combined symptom and medication score. SLIT improves the clinical course of allergic patients although new sensitisations may appear.

Activation of PPAR gamma receptors reduces levodopa-induced dyskinesias in 6-OHDA-lesioned rats.

Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID.

Regulation of cannabinoid receptor gene expression and endocannabinoid levels in lymphocyte subsets by interferon-ß: a longitudinal study in multiple sclerosis patients.

Evidence suggests the involvement of the cannabinoid system in the pathogenesis of multiple sclerosis (MS). We studied cannabinoid receptor (CB)1 and CB2 receptor gene expression in B, natural killer (NK) and T cells from MS patients before and after 1 year of interferon beta therapy, and compared these levels to those of healthy controls. We also measured the production of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and the gene expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in these cells. Prior to interferon therapy, MS patients showed significantly elevated CB2 expression in B cells, but not in T or NK cells. These levels decreased gradually within 6 months to 1 year of interferon treatment. CB1 expression was elevated in all cell subsets, but only reached statistical significance in T cells; all levels decreased progressively over time. Before treatment, AEA but not 2-AG levels were significantly elevated in the three cell populations; after 1 year of treatment, all values decreased to control levels. The expression of FAAH was unchanged. The different expression of cannabinoid receptor genes and the increased level of AEA in lymphocytes point to a possible role of the cannabinoid system in MS immune response and its modulation by interferon.

The spectrum of factor XI deficiency in Italy.

Factor XI (FXI) deficiency is a rare inherited bleeding disorder invariably caused by mutations in the FXI gene. The disorder is rather frequent in Ashkenazi Jews, in whom around 98% of the abnormal alleles is represented by Glu117X and Phe283Leu mutations. A wide heterogeneity of causative mutations has been previously reported in a few FXI deficient patients from Italy. In this article, we enlarge the knowledge on the genetic background of FXI deficiency in Italy. Over 4 years, 22 index cases, eight with severe deficiency and 14 with partial deficiency, have been evaluated. A total of 21 different mutations in 30 disease-associated alleles were identified, 10 of which were novel. Among them, a novel Asp556Gly dysfunctional mutation was also identified. Glu117X was also detected, as previously reported from other patients in Italy, while again Phe283Leu was not identified. A total of 34 heterozygous relatives were also identified. Bleeding tendency was present in very few cases, being inconsistently related to the severity of FXI deficiency in plasma. In conclusion, at variance with other populations, no single major founder effect is present in Italian patients with FXI deficiency.

Serum resistin levels in children with primary snoring.

Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS.

Activity of Thymus vulgaris essential oil against Anisakis larvae.

Anisakiasis is an important food-borne disease especially in countries with high fish consumption. The increase of cases of human disease and the virtual absence of effective treatments have prompted the research on new active compounds against Anisakis larvae. As well known, the disease is related to the consumption of raw or almost raw seafood products, but also marinated and/or salted fishery products, if the processing is insufficient to destroy nematode larvae can represent a risks for the consumers. In the light of the biocidal efficacy against different pathogens demonstrated for various essential oils, the aim of this work is to evaluate the effect of Thymus vulgaris essential oil (TEO) against anisakidae larvae. The TEO at 10% and 5% concentration in oil sunflower seeds, caused in vitro the death of all larvae within 14 h, with cuticle and intestinal wall damages. The results obtained showing a significant activity against Anisakis larvae, suggest further investigation on TEO as a larvicidal agent and on its potential use in the industrial marinating process.

Portable NIR spectroscopy: the route to green analytical chemistry.

There is a growing interest for cost-effective and nondestructive analytical techniques in both research and application fields. The growing approach by near-infrared spectroscopy (NIRs) pushes to develop handheld devices devoted to be easily applied for in situ determinations. Consequently, portable NIR spectrometers actually result definitively recognized as powerful instruments, able to perform nondestructive, online, or in situ analyses, and useful tools characterized by increasingly smaller size, lower cost, higher robustness, easy-to-use by operator, portable and with ergonomic profile. Chemometrics play a fundamental role to obtain useful and meaningful results from NIR spectra. In this review, portable NIRs applications, published in the period 2019-2022, have been selected to indicate starting references. These publications have been chosen among the many examples of the most recent applications to demonstrate the potential of this analytical approach which, not having the need for extraction processes or any other pre-treatment of the sample under examination, can be considered the "true green analytical chemistry" which allows the analysis where the sample to be characterized is located. In the case of industrial processes or plant or animal samples, it is even possible to follow the variation or evolution of fundamental parameters over time. Publications of specific applications in this field continuously appear in the literature, often in unfamiliar journal or in dedicated special issues. This review aims to give starting references, sometimes not easy to be found.

Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990-1999 and 2000-2007 such that during the latter, death rate overlapped that of the general population (SMR 1990-1999: 1.98 95% CI 1.54-2.51; SMR 2000-2007: 1.08 95% CI 0.83-1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000-2007 vs. 64.0 in 1990-1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C-associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.

Conservative vs. surgical approach for degenerative meniscal injuries: a systematic review of clinical evidence.

OBJECTIVE: Analyzing the available evidence by comparing the role of arthroscopic surgery and conservative treatment in the management of degenerative meniscopathy. MATERIALS AND METHODS: A literature search was carried out on the PubMed, EMBASE, Scopus, and PEDro databases in May 2019 to identify all the randomized controlled trials (RCTs) comparing arthroscopic surgery to conservative management of painful but stable degenerated menisci. The quality of the RCTs was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 10 studies, including 1525 patients and dealing with conservative treatment vs. arthroscopic surgery were included in this review. In eight studies the effectiveness of exercise therapy was compared to surgery; in one study the effectiveness of intra-articular steroid injection was compared to surgery; in one study the effectiveness of placebo surgery was compared to partial meniscectomy. In all studies, no significant inter-group difference in terms of knee pain and knee function were observed at any follow-up evaluation. CONCLUSIONS: Degenerative meniscal tears, without symptoms of locking and catching, can be successfully managed by a proper regimen of physical therapy as a first line treatment. Surgical approach might be considered in case of poor response after conservative treatment.

Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes.

Kv1.3 potassium channels maintain the membrane potential of effector memory (T(EM)) T cells that are important mediators of multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. The polypeptide ShK-170 (ShK-L5), containing an N-terminal phosphotyrosine extension of the Stichodactyla helianthus ShK toxin, is a potent and selective blocker of these channels. However, a stability study of ShK-170 showed minor pH-related hydrolysis and oxidation byproducts that were exacerbated by increasing temperatures. We therefore engineered a series of analogs to minimize the formation of these byproducts. The analog with the greatest stability, ShK-192, contains a nonhydrolyzable phosphotyrosine surrogate, a methionine isostere, and a C-terminal amide. ShK-192 shows the same overall fold as ShK, and there is no evidence of any interaction between the N-terminal adduct and the rest of the peptide. The docking configuration of ShK-192 in Kv1.3 shows the N-terminal para-phosphonophenylalanine group lying at the junction of two channel monomers to form a salt bridge with Lys(411) of the channel. ShK-192 blocks Kv1.3 with an IC(50) of 140 pM and exhibits greater than 100-fold selectivity over closely related channels. After a single subcutaneous injection of 100 microg/kg, approximately 100 to 200 pM concentrations of active peptide is detectable in the blood of Lewis rats 24, 48, and 72 h after the injection. ShK-192 effectively inhibits the proliferation of T(EM) cells and suppresses delayed type hypersensitivity when administered at 10 or 100 microg/kg by subcutaneous injection once daily. ShK-192 has potential as a therapeutic for autoimmune diseases mediated by T(EM) cells.

Neurochemical changes in the striatum of dyskinetic rats after administration of the cannabinoid agonist WIN55,212-2.

Chronic use of levodopa, the most effective treatment for Parkinson's disease, causes abnormal involuntary movements named dyskinesias, which are linked to maladaptive changes in plasticity and disturbances of dopamine and glutamate neurotransmission in the basal ganglia. Dyskinesias can be modeled in rats with unilateral 6-hydroxydopamine lesions by repeated administration of low doses of levodopa (6 mg/kg, s.c.). Previous studies from our lab showed that sub-chronic treatment with the cannabinoid agonist WIN55,212-2 attenuates levodopa-induced dyskinesias at doses that do not interfere with physiological motor function. To investigate the neurochemical changes underlying WIN55,212-2 anti-dyskinetic effects, we used in vivo microdialysis to monitor extracellular dopamine and glutamate in the dorsal striatum of both the hemispheres of freely moving 6-hydroxydopamine-treated, SHAM-operated and intact rats receiving levodopa acutely or chronically (11 days), and studied how sub-chronic WIN55,212-2 (1 injection x 3 days, 20 min before levodopa) affected these neurochemical outputs. Our data indicate that: (1) the 6-hydroxydopamine lesion decreases dopamine turnover in the denervated striatum; (2) levodopa injection reduces extracellular glutamate in the side ipsilateral to the lesion of dyskinetic rats; (3) sub-chronic WIN55,212-2 prevents levodopa-induced glutamate volume transmission unbalances across the two hemispheres; and (4) levodopa-induced dyskinesias are inversely correlated with glutamate levels in the denervated striatum. These data indicate that the anti-dyskinetic properties of WIN55,212-2 are accompanied by changes of dopamine and glutamate outputs in the two brain hemispheres of 6-hydroxydopamine-treated rats.

Foreign body reaction to artelon spacer: case report.

Anecdotal reports of painful synovitis after implantation of the Artelon spacer (Small Bone Innovations, Inc., Morrisville, PA) have emerged. The manufacturer claims that this type of reaction is related to the method of fixation and/or to suture material. This report illustrates one case in which a patient exhibited sustained painful synovitis after implantation of the Artelon spacer in the scaphotrapezio-trapezoidal joint, which clinically resolved on removal of the implant. Furthermore, pathology specimens of the soft tissue, synovium, and bone demonstrated an exuberant granulomatous foreign body giant cell reaction to the implant material. Patients should be made aware of the potential of the Artelon spacer to cause a foreign body reaction that may necessitate reoperation for removal of the implant.

Acute pediatric upper extremity compartment syndrome in the absence of fracture.

BACKGROUND: To determine the etiologies and outcomes associated with acute pediatric upper extremity compartment syndrome in the absence of fracture. METHODS: A retrospective review was performed looking at children treated for acute upper extremity compartment syndrome in the absence of fracture at a major teaching hospital. Reason for admission, age, etiology, sensorium, time to fasciotomy, involved compartments, secondary procedures, and functional outcome were recorded. RESULTS: A total of 14 extremities in 13 children with acute compartment syndrome in the absence of fracture were identified over a 22-year period at this single institution. There were 8 boys and 5 girls, with an average age of 7.2 years. Average follow-up was 22 months. Ten patients were being managed in the intensive care unit and had an obtunded sensorium. The cause was iatrogenic in 8 patients, and 2 of these resulted in loss of the involved limb. Six patients required 9 secondary procedures, including 4 amputations, 3 contracture releases, and 2 skin grafts. Of the 3 patients who required a total of 4 amputations, 2 of the patients were in the intensive care unit, and all were younger than 3 years. Only 7 patients had normal hand function. Upon comparing patients with a normal outcome versus those with an abnormal outcome, there was a statistically significant difference if surgery was performed in shorter than 6 hours (P = 0.033). CONCLUSIONS: This problem is often iatrogenic in etiology and can be diagnosed late in this population. An increased level of vigilance should be adopted for this entity because the final outcome can be catastrophic for both the patient and the hospital and early fasciotomy is associated with improved results. LEVEL OF EVIDENCE: Level IV Case Series.

Bacteria isolated from 25 hydatid cysts in sheep, cattle and goats.

Bacteria were isolated from 12 of 25 hydatid cysts collected from the lungs and livers of cattle, sheep and goats slaughtered in the province of Messina, Sicily, Italy. Citrobacter freundii was isolated from seven of the cysts, Aeromonas hydrophila from three, Staphylococcus species from two, Salmonella species from two and Escherichia coli and Proteus vulgaris from one.

Dopamine activation of endogenous cannabinoid signaling in dorsal striatum.

We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D2-like (D2, D3, D4) dopamine receptor agonist quinpirole, a response that was prevented by the D2-like receptor antagonist raclopride. Administration of the D1-like (D1, D5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity.

Comparison Between Folic Acid and gH625 Peptide-Based Functionalization of Fe3O4 Magnetic Nanoparticles for Enhanced Cell Internalization.

A versatile synthetic route based on magnetic Fe3O4 nanoparticle (MNP) prefunctionalization with a phosphonic acid monolayer has been used to covalently bind the gH625 peptide on the nanoparticle surface. gH625 is a membranotropic peptide capable of easily crossing the membranes of various cells including the typical human blood-brain barrier components. A similar synthetic route was used to prepare another class of MNPs having a functional coating based on PEG, rhodamine, and folic acid, a well-known target molecule, to compare the performance of the two cell-penetrating systems (i.e., gH625 and folic acid). Our results demonstrate that the uptake of gH625-decorated MNPs in immortalized human brain microvascular endothelial cells after 24 h is more evident compared to folic acid-functionalized MNPs as evidenced by confocal laser scanning microscopy. On the other hand, both functionalized systems proved capable of being internalized in a brain tumor cell line (i.e., glioblastoma A-172). These findings indicate that the functionalization of MNPs with gH625 improves their endothelial cell internalization, suggesting a viable strategy in designing functional nanostructures capable of first crossing the BBB and, then, of reaching specific tumor brain cells.

High selectivity in new chiral separations of dansyl amino acids by cyclodextrin derivatives in electrokinetic chromatography.

Enantiomeric pairs of 11 dansyl derivatives of alpha-amino acids were used as analytes in electrokinetic chromatography to test the ability as chiral selectors of two pure derivatives of beta-cyclodextrin: the ethylendiamine derivative in primary position (CDen) and a member of a new class of receptors, the cysteamine-bridged hemispherodextrin THCMH. The selectivity obtained by the presence of the hemispherodextrin, appears particularly promising as shown by the large values of resolution obtained. The importance of a detailed analysis of these data is discussed in terms of suggestions for a rational approach to separation science.