Degenerative Phenomena Research Articles

Towards the definition of Transformation Stratigraphic Unit (TSU) as new section of the extended matrix methodology

This study explores the interpretation of degradation and alteration phenomena as stratigraphic units, showing the preliminary results of ongoing research concerning new investigative methods and tools useful to formalize transformative processes on built heritage, in a chronological perspective. Merging conservation sciences with archaeology, the study introduces a new section of the Extended Matrix (EM) method: the Transformation Stratigraphic Unit (TSU). The aim of this work is to assess a new method for documenting and investigating cultural heritage, by generating scientifically reliable reconstructive hypotheses, and by analysing and comparing the mutual interaction of different degenerative phenomena and their relationship. The current workflow, still tentative, utilizes open-source tools and is designed to be replicable and it has been applied to the case study of the architectural complex of S. Pietro in Segni (RM). The current workflow, still tentative, utilizes open-source tools and is designed to be replicable and it has been applied to the case study of the architectural complex of S. Pietro in Segni (RM).

In silico assessment of the reliability and performance of artificial sphincter for urinary incontinence.

The standard artificial urinary sphincter (AUS) is an implantable device for the treatment of urinary incontinence by applying a pressure loading around the urethra through an inflatable cuff, often inducing no-physiological stimulation up to tissue degenerative phenomena. A novel in silico approach is proposed to fill the gap of the traditional procedures by providing tools to quantitatively assess AUS reliability and performance based on AUS-urethra interaction. The approach requires the development of 3D numerical models of AUS and urethra, and experimental investigations to define their mechanical behaviors. Computational analyses are performed to simulate the urethral lumen occlusion by AUS inflation under different pressures, and the lumen opening by applying an intraluminal pressure progressively increased under the AUS action (Abaqus Explicit solver). The AUS reliability is evaluated in terms of tissue stimulation by the mechanical fields potentially responsible for vasoconstriction and tissue damage, while the performance by the intraluminal pressure that causes the lumen opening for a specific occlusive pressure, showing the maximum urethral pressure for which continence is guaranteed. The present study implemented the procedure considering the gold standard AMS 800 and a novel patented AUS. Results provided the comparison between two sphincteric devices and the evaluation of the influence of different building materials and geometrical features on the AUS functionality. The approach was developed for the AUS, but it could be adapted also to artificial sphincters for the treatment of other anatomical dysfunctions, widening the analyzable device configurations and reducing experimental and ethical efforts.

CHANGES IN THE STRUCTURAL ORGANIZATION OF CELLULAR COMPONENTS IN THE RETINAL LAYERS AND LINKS OF ITS HEMOMICOCIRCULATORY BED DURING THE CHRONIC PERIOD OF EXPERIMENTAL OPIOID EXPOSURE AND THE CORRECTION OF THESE CHANGES AT THE ULTRASTRUCTURAL LEVEL

Over the past twenty years, the experimental direction of research has been the most relevant in morphology to study the dynamics of the course of nosologies. In terms of the dynamics of the occurrence of pathomorphological manifestations at the cellular, tissue, organ, and organism levels, it off ers a larger variety of pathology investigations. The study of the retina in the norm and the processes of modifying its structural reorganisation under the eff ect of various nosologies are accorded high importance in the scientifi c literature written by both domestic and international professionals. Despite these eff orts, the problem of opioid retinopathy on prolonged experimental opioid exposure remains essential. It is still unknown, in particular, if the correction of the chronic period of experimental opioid exposure may stabilise pathomorphological symptoms in the retinal layers and linkages of its hemomycrocirculatory bed. The purpose of the research is to fi nd out the features of structural reorganization in the retinal layers and links of its hemomicrocirculatory bed in the chronic period of experimental opioid exposure and the correction of these changes with pentoxifylline.Material and methods. The research used 34 male, sexually mature, non-breeding rats that ranged in weight from 160 to 270 g and were 4.5 to 7.5 months old as its subject matter. The correction dose of pentoxifylline was 2.857 mg/kg. At the end of the 10th week, the material was taken for ultrastructural examination of the retina. Before the sampling of the experimental site material, the animal was withdrawn from the experiment using diethyl ether. The eyeballs of rats were used as a material for ultrastructural examination. Ultrastructural preparations were prepared according to the generally accepted method. As a result of our research of the retina at the end of the tenth week in rats, which were injected with an opioid for six weeks, and subsequently discontinued for four weeks, the phenomena of degeneration of the pigment epithelium, destruction of the membrane discs of the outer segments of the photoreceptors, degenerative changes in the inner segments of the photoreceptors, degenerative and necrotic changes of individual photoreceptors developed. Degeneration and necrosis processes were detected in bipolar and amacrine neurons. Rats were injected with the opioid for six weeks, with its cancellation and subsequent four-week correction with pentoxifylline. After ten weeks of the experiment, degenerative changes in the apical microvilli of the pigment epithelium, destruction of the membrane discs of the outer segments of the photoreceptors, degeneration of bipolar and amacrine neurons, moderately pronounced discirculatory changes, and reactive processes of glial elements were detected. In rats given an opioid for six weeks, followed by four weeks of an opioid with pentoxifylline administration, fl ushing, stasis, and perivascular oedema in the choroidal arteries were established ten weeks later. Degeneration and necrosis of the pigment epithelium, degeneration and destruction of the membrane discs of the outer segments of photoreceptors with separation of individual outer segments, degeneration of the inner segments of photoreceptors, degeneration and necrotic changes of photoreceptors, degeneration and necrotic changes of bipolar and amacryne neurons, Muller cells, degeneration of ganglion neurons, hyperemia, stasis and perivasal oedema in the vessels of the ganglion layer, the layer of nerve fi bers, in the inner mesh layer.

Morphological changes in motoneurons of the oculomotor nucleus of mice after a 30-day space flight and through a 7-day period of readaptation to earth gravity.

The cellular mechanisms of neuroplastic changes in the structure of motoneurons and neuropils of the oculomotor (III) nuclei in mice after a 30-day space flight and 7 days after landing were studied. The results showed that microgravity caused degenerative phenomena in neurons: a decrease in the number of terminal dendritic branches was found both after flight and after readaptation to Earth's gravity. In mice after the flight, the number of axodendritic synapses was less than in the control, and their number was not restored after the readaptation. The number of mitochondria in the motoneurons of animals after the flight also decreased and after the readaptation reached only the control value. In addition, a significant number of dark motorneurons were found in mice after readaptation, which indicates that degeneration was caused not only by microgravity, but also by a reaction to the landing of the biosatellite. On the contrary, in the trochlear nucleus, as we showed earlier (Mikheeva et al. in Brain Res 15(1795):148077. https://doi.org/10.1016/j.brainres.2022.148077 , 2022), after readaptation, the dendrites and synaptic contacts were restored, and mitogenesis is significantly enhanced. It has been suggested that morphological changes in the oculomotor nucleus may be the main cause of microgravity-induced nystagmus.

Heavy and Chronic Cannabis Use Impact on Human Emotions: BOLD-fMRI Study

IntroductionLong term cannabis use has been expanding drastically over the last two decades and has become a major health issue worldwide. Recent studies demonstrate that brain complications in adults with cannabis use are associated with cognitive and emotional impairments, but little is known about the relationship between structural alterations and behavioral manifestations. Therefore, studying the relationship between alterations of emotional system, in parallel with structural degenerative phenomena is very critical.ObjectivesHence, the aim of this study is to demonstrate such alterations by making use of appropriate paradigms during BOLD-fMRI scans. Positive, negative and neutral emotions were examined, in relations with DTI and functional connectivity.Methods11 cannabis addicted patients volunteered for the study. Volunteers were fully healthy. However, any additional comorbidity was a strict criterion of exclusion, and a healthy general state was an indispensable criterion of inclusion. Additionally, it was excluded any patient that have any additional substance use such as tobacco, alcohol, cocaine, etc. And strict use of cannabis was a must.All patients underwent blood and urine assessments to ensure the selection criteria.All patients underwent BOLD-fMRI and anatomical MRI using both motor and emotional paradigm.The motor task consisted of rest alternating with finger tapping. The emotional task included 3 conditions. Positive, neutral and negative were each alternating with silent mental counting. The fMRI data was processed using SPM12 package. A sample of 12 age-matched controls was also included.ResultsThe present results are based on analysis of behavioral and BOLD-fMRI data of 11patients and similar age-matched controls. Analysis of behavioral data showed an alteration of emotional abilities in cannabis addicted patients compared to controls. Analysis of fMRI data revealed significant changes of activation within a large cortical network including prefrontal cortex and parietal cortex, and that emotional responses and BOLD signal were inversely correlated.ConclusionsThese findings demonstrate that the brain of cannabis addicted patients undergoes and emotional alterations that parallel silent structural degenerative phenomena. Although the causal mechanisms are still to be investigated, the fact that functional impairments can be detected in emotional, cognitive and motor domains calls for the development of preventive measures using neurobehavioral tools for this population of patient, and even in at risk users.Disclosure of InterestNone Declared

Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum.

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit. Emerging evidence from animal models of spine degeneration highlight the interdependence of IDD and facet joint OA, warranting a review of the parallels between these two degenerative phenomena for the benefit of both clinicians and research scientists. This Review discusses the pathophysiological aspects of IDD and OA, with an emphasis on tissue, cellular and molecular pathways of degeneration. Although the intervertebral disc and synovial facet joint are biologically distinct structures that are amenable to reductive scientific consideration, substantial overlap exists between the molecular pathways and processes of degeneration (including cartilage destruction, extracellular matrix degeneration and osteophyte formation) that occur at these sites. Thus, researchers, clinicians, advocates and policy-makers should consider viewing the burden and management of spinal degeneration holistically as part of the OA disease continuum.

Elastic fiber degradation as a possible indicator for PMI estimation on mummified and corified skin: a pilot study.

Mummified and corified bodies are particularly complex scenarios to investigate, starting from identifying the post-mortem interval (PMI), even more so in indoor environments. In these bodies, the skin has the peculiar feature to resist for a long time. Among its components, there are elastic fibers, which are characterized by intrinsic resistance to post-mortem degenerative phenomena. Starting from these considerations, we investigated microscopically the persistence, detectability, and changes of elastic fibers in the skin of mummified and corified bodies with different known PMI. The aim was to evaluate whether they could provide an additional tool to aid in PMI estimation in these cases. Therefore, we collected skin samples from mummified or corified bodies found in a domestic environment with different known PMI, as well as from corified bodies that had been exhumed after 11years of burial. Histochemical staining specific for elastic fibers, namely, Weigert's resorcin fuchsin, showed their prolonged persistence and a progressive and different degradation between mummified and corified skin as a function of PMI. Moreover, on the whole, we observed greater preservation of elastic fibers in mummified skin than in corified one at the same PMI. Therefore, histological analysis of elastic fibers in mummified and corified skin may help to provide valuable aid in estimating PMI, especially in those particular cases where more reliable alternatives are lacking.

Visual Pathway Involvement in NMDA Receptor Encephalitis: A Clinical, Optical Coherence Tomography, and 18-Fluorodeoxyglucose PET/CT Approach.

Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94). Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.

A prospective observational study on the beneficial effects and tolerability of a cetylated fatty acids (CFA) complex in a patch formulation for shoulder tendon disorders

BackgroundThe advancement of physiopathological knowledge of tendon structures has shown that, in conditions of overload, there is the onset of both degenerative phenomena, such as the production of metalloproteases, apoptosis of tendon cells and neoangiogenesis, and regenerative and protective phenomena, such as the production of IGF-1 and nitric oxide. Tendinopathy results from the imbalance between these two groups of factors, leading to degeneration, weakening, and fissuring of the tendons, with the presence of local pain. The aim of the study was to evaluate the efficacy and tolerability of cetylated fatty acids (CFA) patch formulation in the control of acute localized shoulder pain and recovery of function in patients with tendinopathies.MethodsA prospective, single-center, no-profit observational study conducted in accordance with Good Clinical Practice. Thirty patients with recent onset shoulder pain symptoms (1–3 months) related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination, was evaluated for shoulder pain and function using the Constant Murley Score. Patients used 1 patch containing CFA for 8 h per day for 10 days. At 10 (V1) and 35 (V2) days after the first visit (V0), the Constant Score, treatment compliance and product tolerability were evaluated.ResultsThirty patients completed the treatment. At V0 the mean Constant Score (CS) was 32.37 ± 11.86, during V1 the mean CS was 50.68 ± 14.30, and at V3 the mean CS was 51.07 ± 15.29. The CS increased significantly between V0 and V1 (p < 0.0001) but did not vary significantly between V1 and V2 (p = 1). The tolerability of the product was excellent.ConclusionsApplication of the CFA-based patch for 10 consecutive days in patients with shoulder tendinopathies was effective in reducing local pain and resulted in a good recovery of function. The results achieved at day 10 were maintained for 25 days, until the follow-up visit at day 35. CFA-based patch, thanks to their efficacy and tolerability, seems to be a promising solution to improve pain and functionality in subject with shoulder tendinopathy.Trial registrationThe study was approved by the Ethics Committee of Azienda USL Toscana Nord Ovest (protocol code 2018RIAB105) and conducted in accordance with Good Clinical Practice and the ethical principles outlined in the Declaration of Helsinki.

Progressive retinal changes in pediatric multiple sclerosis

Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS).Methods We acquired optical coherence tomography (OCT) data (follow-up range: 2 weeks – 5 years, at variable intervals from presentation) in pediatric participants who had multiple sclerosis (MS), monophasic ADS, or were healthy. Multivariable mixed effects models were used to assess the association of the number of demyelinating episodes (either optic neuritis [ON], or non-ON relapses) with changes in retinal nerve fiber layer (RNFL) or ganglion cell layer-inner plexiform layer (GCIPL) thickness.Results 64 OCT sans from 23 MS, and 33 scans from 12 monophasic ADS participants were compared with 68 scans from 62 healthy participants. The first ON episode had the biggest impact on RNFL or GCIPL thickness in monophasic ADS (RNFL: -7.9 µm, CI=5.5, p = 0.0056; GCIPL: -8.4 µm, CI=4.4, p = 0.0002) and MS (RNFL: -16 µm, CI = 3.7, p < 10−6; GCIPL: -15 µm, CI = 2.6, p < 10−6). Non-ON relapses were also associated with small but significant retinal thickness reductions in MS (RNFL: -2.6 µm/relapse, CI = 1.4, p = 0.0003; GCIPL: -2.8 µm/relapse, CI = 0.89, p < 10−6). MS participants showed progressive GCIPL thinning independent of acute demyelinating episodes (-2.7 µm/year, CI = 1.9, p = 0.0058).Conclusions We showed a prominent impact of early ON episodes on OCT measures of neuroaxonal structure in patients with ADS. We also demonstrated negative effects of non-ON relapses, and the presence of chronic retinal neurodegenerative changes, in youth with MS.

Clinical and echocardiographic features of valvular aneurysms

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Valvular aneurysm (VA) is a rare disease whose etiology most frequently includes infective endocarditis but also connective tissue or degenerative myxomatous diseases or traumatism related to a remote surgical procedure. Purpose: Our study aims to describe clinical and echocardiographic features of VA. Methods: 12 years retrospective observational study. Inclusion criteria: patients (pts) found to have a VA by echocardiography (E). A VA was defined as a saccular bulging or a cyst-like outpouching of a valve leaflet that expands and collapses during systole or diastole. The ability of different E techniques in imaging and sizing the valve aneurysm and clinical data were collected. Results: In a 12 years observational period, 12 pts (7 male, 5 female) with a mean age of 41 years ± 16.6 were found to have VA as diagnosed by two experienced readers. In 10 pts there was a diagnosis of IE according to the ESC, AHA criteria. In two pts IE work up was negative. In the patient with definite IE, blood cultures were reported as positive in 7/10 pts (staphylococci 4 pts, Pseudomonas 2 pts, clostridium difficile 1) and 9 pts out of 10 pts underwent surgery and 1 died; all of them had valve replacement except one had mitral valve (MV) repair. Severe regurgitation was found in 9 cases. Associated IE features were: perforation (11 pts), abscess (3pts), vegetation (7pts), fistula (1pt), and embolism (6 pts). Echo features are reported in table 1. Transthoracic E was able to image the VA in only 3/12 pts. Discussion: The spectrum of the VA in our cohort is very unusual. We reported a VA in a bioprosthesis MV not IE related and never described, one case of valvular aneurysm in a bicuspid aortic valve, and 2 cases in the posterior mitral leaflet (PML). The etiology of VA was related to IE as the leading cause (ten in our cohort). In the two pts where no IE was diagnosed, the possible pathogenesis in one patient may have been related to a remote surgical procedure (left atrial dissection) and in the second patient to degenerative phenomena of the MV bioprosthesis. Being the imaging uncommon, it is important to not misinterpret the VA features with large vegetations, cystic lesions, and abscess. Conclusion: In our series, both the typical spectrum of the disease and less common presentations have been found. We reported one of the largest series of VA with never described unusual presentation. 2-dimensional (D) transesophageal E (TEE) was the key E modalities in the diagnosis integrated by 3D TEE allowing an anatomical imaging useful in surgical decision planning. Almost all cases were associated with perforation and severe regurgitation and a high incidence of embolism. All the cases with IE required surgery except one that died while medical therapy and follow up in the other etiologies . The unusual echocardiographic features have to be as early as possible detected in order to let the patient have the best therapeutical interventions. Abstract Table 1: Echocardiographic features Abstract Figure. Valvular aneurysm imaging

Computational Modeling Intervertebral Disc Pathophysiology: A Review

Lower back pain is a medical condition of epidemic proportion, and the degeneration of the intervertebral disc has been identified as a major contributor. The etiology of intervertebral disc (IVD) degeneration is multifactorial, depending on age, cell-mediated molecular degradation processes and genetics, which is accelerated by traumatic or gradual mechanical factors. The complexity of such intertwined biochemical and mechanical processes leading to degeneration makes it difficult to quantitatively identify cause–effect relationships through experiments. Computational modeling of the IVD is a powerful investigative tool since it offers the opportunity to vary, observe and isolate the effects of a wide range of phenomena involved in the degenerative process of discs. This review aims at discussing the main findings of finite element models of IVD pathophysiology with a special focus on the different factors contributing to physical changes typical of degenerative phenomena. Models presented are subdivided into those addressing role of nutritional supply, progressive biochemical alterations stemming from an imbalance between anabolic and catabolic processes, aging and those considering mechanical factors as the primary source that induces morphological change within the disc. Limitations of the current models, as well as opportunities for future computational modeling work are also discussed.

MORPHOLOGICAL FEATURES OF THE LIVER PARENCHYMA IN THE EXPERIMENTAL SUPPLEMENTATION OF RATION WITH THE FOOD ADDITIVES.

The aim: The aim of the paper was the experimental study of the morphological features of albino rat hepatocytes after the consumption of the complex of food additives (monosodium glutamate, sodium nitrite, Ponceau 4R) supplemented into the ration and consumed for four weeks. Materials and methods: The study was performed on 30 outbred albino rats of both genders, weighing 204±0.67 g. The ration of the experimental animals, supplemented with a combination of food additives, namely, monosodium glutamate, Ponceau 4R, sodium nitrate, was consumed for 1 and 4 weeks. The study of the structure of hepathocytes was carried out on traditional histological preparations and preparations stained with Best's carmine. Results: Supplementation of ration with the complex of food additives for one week showed the phenomena of fatty degeneration that dominated in hepatocytes, and in a longer consumption of food additives in the ration (for four weeks), the number of liver cells with the phenomena of hydropic degeneration significantly increased, while individual hepatocytes had signs of irreversible destructive changes. Conclusions: Consumption of the complex of food additives supplemented into the standard ration of laboratory animals for 4 weeks leads to a significant change in the dimensions of the liver cells, a decrease in their glycogen content, and a progressive increase in the number of hepatocytes with alterations.

Association between vitamin D receptor gene polymorphism (rs731236) and aggrecan gene VNTR polymorphism with the risk of lumbar intervertebral disc degeneration.

Background:Low back pain is one of the most common causes of referral to physicians. Lumbar disc degeneration (LDD) is the main cause of back pain in different countries. It seems that genetic factors are more effective than environmental factors in the developing of degenerative phenomena. The aim of this investigation, therefore, was to study the association of the aggrecan gene (ACAN) variable number tandem repeat (VNTR) and the vitamin D receptor (VDR) rs731236 (TaqI) polymorphisms, with lumbar intervertebral disc degeneration in a population in the North of Iran.Methods:In this study, 55 patients with symptomatic intervertebral disk degeneration and 55 control subjects were included. VDR gene polymorphism was genotyped by PCR-based RFLP. The isolated DNA was used to genotype the VNTR of ACAN gene via conventional PCR.Results:For VDR gene polymorphism, the CC genotype (OR=5.337, P=0.019) was significantly higher among the patients compared with the controls, revealing a higher frequency of the C allele in patients compared with controls (OR=2.707, P=0.005). The lower number of frequent repetitions in the VNTR aggrecan gene was associated with a six-time increase of lumbar disc degeneration. Also, high BMI can be considered as an independent factor in the incidence of this disease.Conclusion:Aggrecan gene VNTR polymorphism had an association with degeneration of lumbar intervertebral discs that the shorter VNTR repeats increasing the chance of the disc degeneration in this population in the North of Iran. Moreover, an association between the mutant allele (C) of VDR gene TaqI polymorphism and disc degeneration is found.

Risk factors for the development of degenerative cervical myelopathy: a review of the literature.

Degenerative cervical myelopathy (DCM) encompasses various pathological conditions causing spinal cord (SC) impairment, including spondylosis (multiple level degeneration), degenerative disc disease (DDD), ossification of the posterior longitudinal ligament (OPLL), and ossification of the ligamentum flavum (OLF). It is considered the most common cause of SC dysfunction among the adult population. The degenerative phenomena of DDD, spondylosis, OPLL and OLF, is likely due to both inter-related and distinct factors. Age, cervical alignment, and range of motion, as well as congenital factors such as cervical cord-canal mismatch due to congenital stenosis, Klippel-Feil, Ehler-Danlos, and Down syndromes have been previously reported as potential factors of risk for DCM. The correlation between some comorbidities, such as rheumatoid arthritis and movement disorders (Parkinson disease and cervical dystonia) and DCM, has also been reported; however, the literature remains scare. Other patient-specific factors including smoking, participation in contact sports, regular heavy load carrying on the head, and occupation (e.g. astronauts) have also been suggested as potential risk of myelopathy development. Most of the identified DCM risk factors remain poorly studied however. Further researches will be necessary to strengthen the current knowledge on the subject, especially concerning physical labors in order to identify patients at risk and to develop an effective treatment strategy for preventing this increasing prevalent disorder.

A Monolayer System for the Efficient Generation of Motor Neuron Progenitors and Functional Motor Neurons from Human Pluripotent Stem Cells.

Methods for the conversion of human induced pluripotent stem cells (hiPSCs) into motor neurons (MNs) have opened to the generation of patient-derived in vitro systems that can be exploited for MN disease modelling. However, the lack of simplified and consistent protocols and the fact that hiPSC-derived MNs are often functionally immature yet limit the opportunity to fully take advantage of this technology, especially in research aimed at revealing the disease phenotypes that are manifested in functionally mature cells. In this study, we present a robust, optimized monolayer procedure to rapidly convert hiPSCs into enriched populations of motor neuron progenitor cells (MNPCs) that can be further amplified to produce a large number of cells to cover many experimental needs. These MNPCs can be efficiently differentiated towards mature MNs exhibiting functional electrical and pharmacological neuronal properties. Finally, we report that MN cultures can be long-term maintained, thus offering the opportunity to study degenerative phenomena associated with pathologies involving MNs and their functional, networked activity. These results indicate that our optimized procedure enables the efficient and robust generation of large quantities of MNPCs and functional MNs, providing a valid tool for MNs disease modelling and for drug discovery applications.

Modic changes - An evidence-based, narrative review on its patho-physiology, clinical significance and role in chronic low back pain

ObjectiveLumbar degenerative spinal ailments are the most important causes for chronic low back pain. Modic changes (MC) are vertebral bone marrow signal intensity changes seen on MRI, commonly in association with degenerative disc disease (DDD). Despite being widely studied, majority of issues concerning MC are still controversial. The current narrative, evidence-based review comprehensively discusses the various aspects related to MC. Literature searchAn elaborate search was made using keywords “Modic changes”, “lumbar Modic changes”, “Modic changes in lumbar spine”, and “vertebral Endplate Spinal Changes”, on pubmed and google (scholar.google.com) databases on the 3rd of March 2020. We identified crucial questions regarding Modic changes and included relevant articles pertaining to these topics for this narrative review. ResultsThe initial search using the keywords “Modic changes”, “lumbar Modic changes”, “Modic changes in lumbar spine”, and “vertebral Endplate Spinal Changes” on pubmed yielded a total of 568, 412, 394 and 216 articles on “pubmed” database, respectively. A similar search using the aforementioned keywords yielded a total of 3650, 3548, 3726 and 21570 articles on “google scholar” database. The initial screening involved exclusion of duplicate articles, articles unrelated to MC, animal or other non-clinical studies, and articles in non-English literature based on abstracts or the titles of articles. This initial screening resulted in the identification of 405 articles. Full manuscripts were obtained for all these selected articles and thoroughly scrutinised at the second stage of article selection. All articles not concerning Modic changes, not pertaining to concerned questions, articles concerning other degenerative phenomena, articles discussing cervical or thoracic MC, case reports or animal studies, articles in non-English language and duplicate articles were excluded. Review articles, randomised controlled trials and level 1 studies were given preference. Overall, 69 articles were included in this review. ConclusionModic change (MC) is a dynamic phenomenon and its true etiology is still not definitely known. Disc/end plate injury, occult discitis and autoimmune reactions seem to trigger an inflammatory cascade, which leads to their development. Male sex, older age, diabetes mellitus, genetic factors, smoking, obesity, spinal deformities, higher occupational loads and DDD are known risk factors. There is no conclusive evidence on the causative role of MC in chronic low back pain (LBP) or any influence on the long term outcome in patients with LBP or lumbar disc herniations (LDH). Patients with MC have been reported to have less satisfactory outcome following conservative treatment or discectomy, although the evidence is still unclear.

Investigation of interaction phenomena between lower urinary tract and artificial urinary sphincter in consideration of urethral tissues degeneration.

Lower urinary tract dysfunction pertains to symptoms related to the lower urinary tract (LUT), with consequent incontinence. Artificial urinary sphincters (AUS) are adopted to obtain continence conditions, mainly in male subjects, via urethral occlusion by applying pressure load, mostly operating on the basis of an empirical approach. Considering the frequent access of elderly patients to this surgical practice, tissue degradation related to aging phenomena must be investigated. Computational models of the LUT structures and the AUS systems have been designed to evaluate tissues mechanical stimulation and degenerative phenomena for reciprocal interaction. Virtual solid models of the LUT have been developed starting from biomedical images, as histological/morphometrical data. Segmentation procedures have been exploited to provide the three-dimensional reconstruction, and subsequent discretization techniques led to the finite element model. Contemporarily, a finite element model of a typical AUS device was developed. Numerical analyses have been performed to analyze interaction phenomena between AUS and LUT. Different conditions were investigated, modifying both loading conditions, as intraluminal pressure and AUS action, and urethral tissues properties. Particular attention was devoted to tissues parameters, aiming to evaluate the influence of tissues degeneration because of aging and/or pathologies.

Oxytocin may have a therapeutical potential against cardiovascular disease. Possible pharmaceutical and behavioral approaches

Based on the ancient role of oxytocin and its homologues as amplifiers of reproduction we argue for an evolutionary coupling of oxytocin to signaling pathway which support restorative mechanisms of cells and tissue. In particular, the survival and function of different categories of stem cells and primordial cells are enhanced by mitogen-activated protein kinase (MAPK) pathways. Furthermore, oxytocin stimulates the AMP-activated protein kinase pathway (AMPK) in numerous of cell types which promotes the maintenance of different cell structures. This involves autophagic processes and, in particular, may support the renewal of mitochondria. Mitochondrial fitness may protect against oxidative and inflammatory stress - a well-documented effect of oxytocin. The combined specific trophic and protective effects oxytocin may delay several degenerative phenomena including sarcopenia, type-2 diabetes and atherosclerosis. These effects may be exerted both on a central level supporting the function and integrity of the hypothalamus and peripherally acting directly on blood vessels, pancreas, heart, skeletal muscles and adipose tissue etc. Furthermore, in the capacity of being both a hormone and neuromodulator, oxytocin interacts with numerous of regulatory mechanisms particularly the autonomic nervous system and HPA-axis which may reduce blood pressure and affect the immune function. The potential of the oxytocin system as a behavioral and molecular target for the prevention and treatment of cardiovascular disease is discussed. Focus is put on the affiliative and sexual significance and the different options and limitations associated with a pharmaceutical approach.MeSH: Aging, Atherosclerosis, Heart, Hypothalamus, Inflammation, Love, Orgasm, Oxytocin.

Villa San Marco at Stabia. Dynamics of decay and perspectives for deepening and safeguarding

The site of Villa San Marco in the archaeological area of Stabiae, offers a wide repertoire of degenerative situations with multiple levels of criticality and complexity and a differentiated stratification. Damage related to the known eruptive events of Vesuvius are the substratum to phenomena of deterioration activated by excavations of the Bourbon period, restoration and protection interventions that were not always adequate and efficient and by widespread abandonment conditions at the end of the excavation. Flora, anthropic environment, water, atmospheric agents, slope instability, seismic phenomena, combine with the technological characteristics of this architectural complex, triggering degenerative processes at different speeds and intensities. A study initiated in collaboration between the University of Florence and the Archaeological Park of Pompeii aims at the knowledge of the degenerative dynamics of the site in order to develop risk management and control systems aimed at safety of use and maintenance. Investigations disseminated in the villa and detailed on specific portions have begun to create a clearer picture of conservation issues. The digital documentation of the structures has been flanked by a phase of on field investigation aimed at an assessment of the degenerative phenomena, at the analytical verification and at the interpretation of the structural instability. The research perspective is to define a multi-scale survey approach that allows to extract data useful for the quantification of the risk, through a systematic understanding of the vulnerabilities of the elements involved (walls, columns, blocks, decorated surfaces, earthen layers, etc).