design of a new intervertebral disc prosthesis a numerical approach

Abstract In the degenerative disc disease, an alternative treatment to the traditional arthrodesis, consisting in the fusion of the two adjacent vertebral bodies, is the artificial intervertebral disc. The advantage of an artificial intervertebral disc is that the d.o.f. of the vertebral segment can be saved and the mobility of the spine could be almost restored. Many solutions were proposed in the last decades, most of them consisting in metallic rigid joints able to assure the mobility and to maintain the correct distance between the vertebrae but subject to corrosion, wear and interface problems due to the different stiffness with the biological tissues. Purpose of this paper is the design of a prosthetic device substituting the disc to be placed in the intervertebral zone. Different types of artificial prostheses have been proposed by the authors, based on similarity with physiological discs, then with a central part (nucleus) made of hyperelastic material and an outer containment frame (annulus) consisting of a plastic material with a stiffness high enough to assure the reaction force and to avoid large radial displacements. In our solutions, the external parts (annulus and plates) were modeled by HDPE and the inner part (nucleus) by silicone and hydrogel. All the materials are highly biocompatible. The intention of the authors, moreover, is to permit an easier surgical technique. The prosthesis, in fact, could be mounted void of the nucleus, allowing an easier placement, and filled only after the frame insertion, by injecting the silicone through a syringe. The nucleus was modeled by the Mooney-Rivlin parameters related to elastomers, being the disc subject to large deformations that the materials have to be able to withstand in elastic conditions. The discs are subjected to compressive loads either in the mounting phase or, after the silicone filling, due to the physiological loads

An autoregulatory loop controls the expression of the transcription factor NF-Y

The heterotrimeric NF-Y complex is a pioneer factor that binds to CCAAT-genes and regulates their transcription. NF-Y cooperates with multiple transcription factors and co-regulators in order to positively or negatively influence gene transcription. The recruitment of NF-Y to CCAAT box is significantly enriched in cancer-associated gene promoters loci and positively correlates with malignancy. NF-Y subunits, in particular the DNA-binding subunit NF-YA and the histone-fold subunit NF-YC, appear overexpressed in specific types of cancer. Here we demonstrate that NF-Y subunits expression is finely regulated through transcriptional and post-translational mechanisms thus allowing control over basal expression levels. NF-Y negatively regulates the transcription of the genes encoding for its subunits. DNA pull-down/affinity purification assay coupled with Mass Spectrometry identified putative co-regulators, such as Lamin A, involved in NF-YA gene transcription level. We also evidentiate how the stability of the complex is severely affected by the absence of one subunit. Our results identified for the first time one of the mechanisms responsible for NF-Y expression, which may be involved in the aberrant expression and activity observed in tumor cells and other pathological conditions

[Organizational and financial aspects of the introduction of Botox® in the clinical diagnostic therapeutic process of chronic migraine at a Local Health Unit in Italy]

BACKGROUND: Existing literature shows that the use of Botox®/onabotulinumtoxinA (BT) in chronic migraine (CM) is promising from a cost-effectiveness standpoint and the use of a clinical diagnostic therapeutic process (CDTP) dedicated to CM allows a reduction of pathology costs. The inclusion of BT in chronic migraine therapy at a Roman ASL involves the need to investigate the real treatment costs of a CDTP and to measure how a targeted organizational CDTP strategy for CM allows insuring treatment accessibility, sustainability, and appropriateness.OBJECTIVE: To conduct a cost-effectiveness analysis of providing administration of BT in patients with CM using real world data from an ASL in Rome.METHODS: The real world cost data for approximately 215 anonymous patients were summarized. The cost data were extrapolated from the database of the ASL and they populated a Markov decision model developed by Allergan. The analysis is based on a decision model populated with real drug and service cost data, for the years 2010-2012. The financial assessment was conducted from the viewpoint of the Italian National Health Service.RESULTS: Over a 2 year temporal horizon, incremental BT costs, compared to a placebo, are equal to € 261 against an incremental gain of 0.0655 QALY in favor of BT. The ratio between costs and incremental QALY generates an ICER of 3,983 €/QALY, favorable and below the acceptability threshold used by many countries for reimbursement decisions (25,000-40,000 € per QALY gained).CONCLUSIONS: The inclusion of BT in the CDTP dedicated to CM of an Italian ASL improves both clinical outcomes of the patients and the allocation of the SSN available resources.[Article in Italian

Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration

In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent-non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions

Anti-HPV vaccination in women treated for HPV-related lesions: effective vaccination strategy for achieving HPV-related diseases control

Human Papillomavirus (HPV) vaccination is able to reduce the risk of relapse in women undergoing surgery for HPVrelated lesions. The surgical treatment of these lesions can correlate with a greater risk of preterm parts. The extension of the recommendation of HPV vaccination to patients treated for a previous HPV-related lesion would entail a lower expense for the Health System. Therefore, an increase in the use of HPV vaccination is desirable also in this target population as well as the implementation of a care pathway dedicated to women treated for HPV lesions that includes vaccination in the prevention activities of relapses

Economic Aspects in the Management of Diabetic Macular Edema in Italy

BackgroundDiabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant. MethodsThe analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison. ResultsThe increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by euro2,058,238 in 5 years. ConclusionsTo optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society

The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle

Satellite cells represent myogenic stem cells that allow the homeostasis and repair of adult skeletal muscle. Here the authors report that the transcription factor NF-Y is expressed in satellite cells and is important for their maintenance and proper myogenic differentiation

The cerebellum-periaqueductal gray connectivity: a constrained spherical deconvolution tractography study

The periaqueductal gray (PAG) is a relevant neuronal station situated in the midbrain, which play a pivotal role in triggering behavioral responses to stressful stimuli, such as pain or threat. Current knowledge concerning PAG functions is based on several tract-tracing studies conducted on animals, which unveiled PAG connectivity to both cortical and subcortical areas [1]. Considering that descending projections to spinal cord reach the dorsal horn and connections to motor related cortical areas have never been described yet, the neural structure which best fits PAG modulation of motor behavior is the cerebellum. Direct connections between PAG and cerebellar cortex were firstly described in cats and neurophysiological studies conducted on animals, suggesting either direct or undirect PAG influence to cerebellar activity. In the last decades, the rise of diffusion weighted imaging and tractography have made possible to reliably reconstruct white matter pathways in the human brain. To the best of our knowledge, few tractography studies explored PAG connectivity in humans and the evidences concerning direct or undirect connections with the cerebellar cortex are still sparse. Aimed at investigating PAG connectivity with particular focus on PAG-cerebellum connections, we used high quality diffusion weighted imaging data of thirty healthy subjects from the Human Connectome Project. Fiber tracts have been reconstructed using Spherical Informed Filtering of Tractograms, a novel algorithm improving streamline reconstruction and selection [2]. Connectivity analysis revealed that the PAG is mainly connected with subcortical structures, such as the thalamus and the cerebellum. Taken together our results show a direct interplay between the PAG and the cerebellum, thus suggesting the cerebellum as a likely candidate to modulate complex features of motor behavior in stressful conditions, such as adaptation after social defeat and computing strategies to avoid threatening situations

Are Nutraceuticals Effective in COVID‐19 and Post‐COVID Prevention and Treatment?

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID‐19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID‐19 led to increasing importance of a new disease called post‐COVID syndrome. The term post‐COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID‐19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID‐19 disease and post‐COVID syndrome