Side Arm Homicide in the Italian Province of Trieste between 1953 and 2002

The authors present a complete overview of the phenomenon of side arm homicide, basing the study on the data collected at the Forensic Pathology Unit of the University Of Trieste School Of Medicine. Side arms are the most frequently used homicidal method in the town and province of Trieste in a considered study period of 50 years from 1953 to 2002. The analysis of the collected data shows that the town and province of Trieste are communities still very well disjoined from a reality in which crimes against life are yet very uncommon occurrences. This conclusion is well supported by the fact that it has not been possible to define a category of potential victims, which is on the contrary quite easy among societies where organized crime is consistent and widespread. The popularity of side arm as homicide method in our province supports the hypothesis that these crimes are often not aforethought murders, perpetrated by subjects often afflicted by recorded mental health problems, acting during an insanity raptus. Knives are not only actually the easiest weapons to obtain in a household, but are very easily used as well, even by the subjects not accustomed to handle weapons

Meniscus Matrix Remodeling in Response to Compressive Forces in Dogs

Joint motion and postnatal stress of weight bearing are the principal factors that determine the phenotypical and architectural changes that characterize the maturation process of the meniscus. In this study, the effect of compressive forces on the meniscus will be evaluated in a litter of 12 Dobermann Pinschers, of approximately 2 months of age, euthanized as affected by the quadriceps contracture muscle syndrome of a single limb focusing on extracellular matrix remodeling and cell-extracellular matrix interaction (i.e., meniscal cells maturation, collagen fibers typology and arrangement). The affected limbs were considered as models of continuous compression while the physiologic loaded limbs were considered as controls. The results of this study suggest that a compressive continuous force, applied to the native meniscal cells, triggers an early maturation of the cellular phenotype, at the expense of the proper organization of collagen fibers. Nevertheless, an application of a compressive force could be useful in the engineering process of meniscal tissue in order to induce a faster achievement of the mature cellular phenotype and, consequently, the earlier production of the fundamental extracellular matrix (ECM), in order to improve cellular viability and adhesion of the cells within a hypothetical synthetic scaffold

The challenge of the identification of a new mineral species: example "Pezzottaite"

In 2002, a new gem mineral of commercial importance was discovered. In accordance with the need for all new mineral discoveries to be scientifically characterized (see Nickel and Grice, 1998), the gemological community anxiously awaited the results of tests to positively identify the new mineral (Hawthorne et al., 2003, Hawthorne et al., submitted and Laurs et al., 2003). This period of analysis brought into play the question: Exactly what procedures are necessary for the positive characterization of a new mineral

Hypoxia as a stimulus upon neonatal swinemeniscus cells: highway to phenotypic maturation of meniscal fibro-chondrocytes?

Menisci are essential structures in the knee joint where they cover fundamental biomechanical and protective roles (1-3). Menisci are characterized by a peculiar structure that, on one hand, allow them to perform their particular role in the stifle joint, but simultaneously make them a very challenging structure to deal with (2). Immature menisci are featured by numerously elongated cells (fibrocytes-like) in a disorganized matrix composed almost completely of collagen type I and few glycosaminoglycans (GAGs) and have a rich vascularization, on the other hand, mature and functional menisci are characterized by few round-shaped cells,a matrix rich of well ordinated collagen fibres (above all collagen type II) and GAGs, and preserve vascularization only in the outer zone (aka red zone) (1). Great interest, in both human and veterinary medicines, is reserved to the treatment of the injuries of the inner and avascular zone (aka white zone) of the meniscus: until now, there are no perfect solutions for the regeneration or the replacement of this tissue once injured (3). This work is focused on the utilization of an environmental factor like hypoxia in meniscal tissue culture, in order to evaluate if it could be utilized to improve meniscal culture with a view to tissue engineering. Ninety menisci from neonatal pigs (day 0) were harvested and cultured under two different atmospheric conditions (hypoxia with 1% O2 and normoxia) until 14 days. Samples were analysed at 0, 7 and 14 days through histochemical (Safranin-O staining), immunofluorescence and RT-PCR (Sox-9, Hif-1a, Hif-2, Collagen I and II, both methods) and biochemical (DNA, GAGs, DNA/GAGs ratio) techniques to record any possible differences in maturation of meniscal cells. Safranin-O staining allowed to show an increment in matrix deposition and round-shape \u201cfibro-chondrocytic\u201d cells quantity of hypoxia-cultured menisci respect to controls under normal atmospheric conditions. The same maturation shifting was observed by means of immunofluorescence and RT-PCR analysis, characterized by an increment of Sox-9 and collagen II, moving from day zero to 14-days under hypoxic environment, and by biochemical analysis,with an increment of DNA/GAGs ratio typical of mature meniscal tissue (characterized by few cells and much GAGs). This study shows that hypoxia can be considered as a booster to achieve meniscal cells maturation and opens considerably opportunities in the field of meniscus tissue engineering. References 1. Dai Z, et al. J Orthop Res 2013 ;31:1514-9, 2. Fox AJS, et al. Clin Anat 2015 ;28:269-87 3. Sosio C, et al. Tissue Eng Part A 2015 ;21:3-4

Meniscus maturation in the swine model: role of endostatin in cellular differentiation

The development of an engineered meniscus derives from the need to regenerate a tissue which is largely unable to self-repair with consequent loss of functionality. Hence a deeper knowledge of the native meniscus morphology and biomechanics in its different regions, including molecules involved in regulation of the maturation process, is essential. The meniscus is a complex tissue, displaying great regional variation in extracellular matrix components and in vascularization, as a result of several biomechanical stimuli. Its biochemical composition is modulated to adapt the tissue to the different functions that are required throughout growth, until a \u201cmature\u201d phase is reached in adulthood. The aim of this work is to evaluate the biological role of Endostatin in the regulation of angiogenesis as in the fibro-chondrogenic differentiation of neonatal meniscal cells in the pig. The swine is an attractive model for meniscal repair studies, as its knee joint is closely comparable to the human one in terms of anatomical structure, vascularization, and healing potential. Our preliminary data show that Endostatin contributes to the acquisition of chondrocyte phenotype in an undifferentiated but committed cellular population. Thus, a better understanding of the role of Endostatin in cell metabolism might lead to a deeper knowledge of the events regulating meniscus maturation. These findings may be crucial for the development of an engineered scaffold able to induce meniscal cell differentiation by releasing Endostatin-rich microspheres

Ultrastructural and matrix evaluation of morpho-functional age-related changes in dog meniscus

Menisci are essential structures for the knee joint. Different attempts were made trying to replace or regenerate the meniscus after its tear, but the perfect solution is still far away. A better knowledge of the physiologic development of this structure through time could be useful to understand its behavior in the light of the tissue bio-engineering. In this study, the changes in canine meniscal morphology were evaluated to assess how it varies among diverse age stages. The fibers arrangement and matrix deposition in canine menisci from neonatal (died at birth), 10-days, 30-days and adult dogs, dead for causes not related to the present study, were evaluated by means of histochemistry (safranin-O and Sirius red staining), polarized light microscopy, immunofluorescence (collagen I and II) and Scanning Electron Microscopy (SEM). Moreover, quantitative measurements of glycosaminoglycans (GAGs), DNA and GAGs/DNA ratio were performed. The \u201cknotty\u201d structure of neonatal meniscus is probably due to balls of collagen fibres that are not completely stretched until the 30-days stage (Fig 1). The stretching of the fibres starts from the inner portion that is probably the first and the most compressed zone. Safranin-O staining shows how matrix composition vary during growth. Neonatal meniscus is characterized by a huge number of elongated cells (fibroblast-like) and GAGs, features that characterized a still afunctional tissue. With growth, more and more cells assumed a rounded shape. The end-point of the maturation process is represented by the adult meniscus: it is characterized by almost only rounded cells (fibro-chondrocyte-like), in small number, and surrounded by matrix (Fig 1). Nevertheless, 10-30 days interval could be considered the starting point of the meniscus specialization and maturation. Fibres arrangement starts like balls of collagen fibres that follow a disorganized pattern in the neonatal meniscus (Fig 1). In 10-days meniscus, these balls of fibres tend to disappear starting from the meniscus\u2019 inner portion, in association with an initial organization of the fibres according to the longitudinal and radial axes of the meniscus. The organization of fibres network is almost complete at 30-days of life, when all the fibres follow the two main axes of the meniscus and show a well-organized disposition, as seen in adult meniscus. Through the double immunofluorescence it is possible to recognized different aspect of maturation (Fig 3). Neonatal meniscus shows almost only collagen type I fibres. Collagen type I and II co-expression starts at 10 days (yellow) and become more evident in 30-days meniscus in which even a differentiation of the inner and the outer zone starts. The same differentiation persist in adult meniscus that is characterized by a frankly fibro-chondrocitic-like cellular phenotype. Biochemical analysis confirmed that cellularity decrease over the time starting from neonatal to adult (Fig 3). The same decreasing trend is observed in GAGs deposition. Even if 30-days meniscus present a lot of common characteristics with the adult one, the GAGs/DNA ratios show how the latter is the only that present a maturely functional tissue in which a small number of cells is able to produce a matrix rich of GAGs. Meniscal structure changes during growth. The starting point is represented by the neonatal tissue, rich of immature cells and with poor expression of matrix components. The end-point is the adult tissue, characterized by phenotypically mature cells, which assure a functional matrix deposition. Ten-thirty days interval seems to be the turning point of this developmental process. This work highlights how dog meniscal structure changes its morphology among different age stages; this fact may suggest a role of the biomechanical forces, physiologically acting on meniscus, in the development of its ultimate shape and functions. The knowledge of the developmental process of a structure has a capital importance to comprehend its physiologic anatomy and function

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial

AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy)

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

Background: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.Patients and methods: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed.Results: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021 were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three-(81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction &gt;89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS &gt;10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS.Conclusions: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed