Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity.

Purkinje cells in the cerebellum are among the largest neurons in the brain and have been extensively investigated in rodents. However, their morphological and physiological properties remain poorly understood in humans. In this study, we utilized high-resolution morphological reconstructions and unique electrophysiological recordings of human Purkinje cells ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human Purkinje cell had similar fractal structures but were larger than those of mouse Purkinje cells. Consequently, given a similar spine density (2/µm), human Purkinje cell hosted approximately 7.5 times more dendritic spines than those of mice. Moreover, human Purkinje cells had a higher dendritic complexity than mouse Purkinje cells and usually emitted 2-3 main dendritic trunks instead of one. Intrinsic electro-responsiveness was similar between the two species, but model simulations revealed that the dendrites could process ~6.5 times (n = 51 vs. n = 8) more input patterns in human Purkinje cells than in mouse Purkinje cells. Thus, while human Purkinje cells maintained spike discharge properties similar to those of rodents during evolution, they developed more complex dendrites, enhancing computational capacity.

Editorial: Sharks and Skates-Ecology, Distribution and Conservation.

The class Chondrichthyes (sharks, rays and chimeras) is one of the three lineages of fishes and the most evolutionary distinct radiation of vertebrates [...].

Model simulations unveil the structure-function-dynamics relationship of the cerebellar cortical microcircuit.

The cerebellar network is renowned for its regular architecture that has inspired foundational computational theories. However, the relationship between circuit structure, function and dynamics remains elusive. To tackle the issue, we developed an advanced computational modeling framework that allows us to reconstruct and simulate the structure and function of the mouse cerebellar cortex using morphologically realistic multi-compartmental neuron models. The cerebellar connectome is generated through appropriate connection rules, unifying a collection of scattered experimental data into a coherent construct and providing a new model-based ground-truth about circuit organization. Naturalistic background and sensory-burst stimulation are used for functional validation against recordings in vivo, monitoring the impact of cellular mechanisms on signal propagation, inhibitory control, and long-term synaptic plasticity. Our simulations show how mossy fibers entrain the local neuronal microcircuit, boosting the formation of columns of activity travelling from the granular to the molecular layer providing a new resource for the investigation of local microcircuit computation and of the neural correlates of behavior.

Computational models of neurotransmission at cerebellar synapses unveil the impact on network computation.

The neuroscientific field benefits from the conjoint evolution of experimental and computational techniques, allowing for the reconstruction and simulation of complex models of neurons and synapses. Chemical synapses are characterized by presynaptic vesicle cycling, neurotransmitter diffusion, and postsynaptic receptor activation, which eventually lead to postsynaptic currents and subsequent membrane potential changes. These mechanisms have been accurately modeled for different synapses and receptor types (AMPA, NMDA, and GABA) of the cerebellar cortical network, allowing simulation of their impact on computation. Of special relevance is short-term synaptic plasticity, which generates spatiotemporal filtering in local microcircuits and controls burst transmission and information flow through the network. Here, we present how data-driven computational models recapitulate the properties of neurotransmission at cerebellar synapses. The simulation of microcircuit models is starting to reveal how diverse synaptic mechanisms shape the spatiotemporal profiles of circuit activity and computation.

Movement patterns analysis as a tool in Fully Protected Areas design: Influence of relocations on travelled distances of Palinurus elephas (Fabr. 1787) in Sardinian FPAs (central-western Mediterranean).

Effectiveness of restocking programs in Marine Fully Protected Areas' (FPAs) can be highly affected by the movement behavior of the species to protect. We analyzed the data of 744 Palinurus elephas specimens tagged, relocated inside 12 FPAs, established in the seas surrounding Sardinia (central-western Mediterranean), and then recaptured. The overall aims were to characterize the individuals' movements after the relocation and to discuss strengths and weaknesses of the current FPAs' design. Almost 80% of tagged individuals travelled progressively increasing distances, as a function of the release distance, up to a maximum value of 11,500 m. Then, for larger release distances, individuals' mobility appeared reduced and more chaotic. A similar trend was found analyzing the distances travelled with respect to the FPAs with the highest number of recaptured individuals and to the size. These results allow to establish a threshold limit of the release distance, to take into account when designing FPAs, as a useful tool to keep a portion of the individuals into FPAs' borders, in order to both preserve the species and guarantee a spillover of individuals in the commercial areas.

The Use of Reproductive Indicators for Conservation Purposes: The Case Study of Palinurus elephas in Two Fully Protected Areas and Their Surrounding Zones (Central-Western Mediterranean).

In 1990s, the European spiny lobster Palinurus elephas, one of the most commercially important species in the Mediterranean, exhibited a population decline. For this reason, fully protected areas (FPAs) appeared effective in re-establishing natural populations and supporting fishery-management objectives. Here, the reproductive parameters of P. elephas populations in two different FPAs (Su Pallosu and Buggerru, central-western Mediterranean), where a restocking programme was carried out, and in their surrounding commercial zones, were investigated from quantitative and qualitative perspectives. The comparison of fecundity between females collected inside and outside FPAs did not show statistical differences as well as the vitellogenin concentration, which did not vary among eggs of different size classes of females caught inside and outside the FPAs, indicating the same reproductive potential. The study demonstrated a benefit of overexploited populations in terms of enhancement of egg production overtime (15 years for Su Pallosu and 6 years for Buggerru) with a mean egg production 4.25-5.5 times higher at the end of the study than that observed at the beginning of the study. The main driver of eggs production appeared to be size, with larger lobsters more present inside the FPAs than outside. Given these results, the dominant contribution of the two studied FPAs to the regional lobster reproduction is remarkable.

Metacarpophalangeal joint hyperextension in rhizartrosis: is surgical correction necessary?

BACKGROUND AND AIM: Rhizarthrosis represents 10% of all arthritic manifestations and its prevalence increases with age and in women. The hyperextension of the metacarpophalangeal joint (MCPj) is consequent to a progressive dorsoradial subluxation of the trapeziometacarpal joint (TMj) in advanced osteoarthritis. The aim of this retrospective study is to evaluate the clinical and functional results of 32 patients affected by advanced rhizarthrosis who underwent to modified Burton-Pellegrini's trapeziectomy in absence of surgical correction of MCPj hyperextension in order to understand when this last step is really necessary. METHODS: Patients were assessed trough DASH and PRWHE questionnaires; the functionality of the hand was assessed by carrying out specific test (grip strength, key-pinch, kapandji test, reduction of wrist flexion strength) and the degree of MCP joint hyperextension was recorded. RESULTS: Clinical evaluation and individual satisfactory were positive in most cases (mean DASH 19 and mean PRWHE 21.8, with a reduction of 77% of VAS pain score). Kapandji test was excellent in 26 patients and grip strength and key pinch were stackable in operated and non-operated hands. Twenty-five out 32 patients presented a MCP joint hyperextension between 0° and 5°, 5 of 10° and other 2 of 15°. CONCLUSION: Modified Burton-Pellegrini's trapeziectomy is a valid option to treat patient with TMj osteoarthritis. The absence of surgical correction of the MCPj does not affect clinical and functional results in deformities <15°.

Advanced MR Imaging for Knee Osteoarthritis: A Review on Local and Brain Effects.

Knee osteoarthritis is one of the leading causes of chronic disability worldwide and is a significant social and economic burden on healthcare systems; hence it has become essential to develop methods to identify patients at risk for developing knee osteoarthritis at an early stage. Standard morphological MRI sequences are focused mostly on alterations seen in advanced stages of osteoarthritis. However, they possess low sensitivity for early, subtle, and potentially reversible changes of the degenerative process. In this review, we have summarized the state of the art with regard to innovative quantitative MRI techniques that exploit objective and quantifiable biomarkers to identify subtle alterations that occur in early stages of osteoarthritis in knee cartilage before any morphological alteration occurs and to capture potential effects on the brain. These novel MRI imaging tools are believed to have great potential for improving the current standard of care, but further research is needed to address limitations before these compositional techniques can be robustly applied in research and clinical settings.

A Taxonomic Survey of Female Oviducal Glands in Chondrichthyes: A Comparative Overview of Microanatomy in the Two Reproductive Modes.

Oviducal glands (OGs) are distinct expanded regions of the anterior portion of the oviduct, commonly found in chondrichthyans, which play a key role in the production of the egg in-vestments and in the female sperm storage (FSS). The FSS phenomenon has implications for understanding the reproductive ecology and management of exploited populations, but little information is available on its taxonomic extent. For the first time, mature OGs from three lecithotrophic oviparous and four yolk-sac viviparous species, all considered at risk from the fishing impacts in the central western Mediterranean Sea, were examined using light microscopy. The OG microanatomy, whose morphology is generally conserved in all species, shows differences within the two reproductive modalities. Oviparous species show a more developed baffle zone in respect to viviparous ones because of the production of different egg envelopes produced. Among oviparous species, Raja polystigma and Chimaera monstrosa show presence of sperm, but not sperm storage as observed, instead, in Galeus melastomus and in all the viviparous sharks, which preserve sperm inside of specialized structures in the terminal zone.

Bio-Ecological Features Update on Eleven Rare Cartilaginous Fish in the Central-Western Mediterranean Sea as a Contribution for Their Conservation.

Cartilaginous fish are commonly recognized as key species in marine ecosystems for their fundamental ecological role as top predators. Nevertheless, effective management plans for cartilaginous fish are still missing, due to the lack of knowledge on their abundance, distribution or even life-history. In this regard, this paper aims at providing new information on the life-history traits, such as age, maturity, reproductive period, in addition to diet characteristics of eleven rare cartilaginous fish inhabiting the Central-Western Mediterranean Sea belonging to the orders Chimaeriformes (Chimaera monstrosa), Hexanchiformes (Heptranchias perlo and Hexanchus griseus), Myliobatiformes (Aetomylaeus bovinus and Myliobatis aquila), Rajiformes (Dipturus nidarosiensis and Leucoraja circularis), Squaliformes (Centrophorus uyato, Dalatias licha and Oxynotus centrina) and Torpediniformes (Tetronarce nobiliana), useful for their assessment and for future management actions. Particularly, the present paper provides for the first time the age estimation of D. nidarosienis and L. circularis which were both found capable of becoming older than ten years. In addition, the present study updates the sizes of first maturity of C. uyato and D. licha, which appeared to be capable of reproducing earlier than what was previously hypothesized, representing very valuable information for a better understanding of these rare species populations status and, eventually, their conservation. On the basis of the stomach content analysis, it was possible to identify five different predator groups.

New insights into life-history traits of Mediterranean Electric rays (Torpediniformes: Torpedinidae) as a contribution to their conservation.

Despite being commonly recognized by the general public, knowledge about the biology and life-history of electric rays is still scarce. Globally, according to the International Union for Conservation of Nature, more of the 80% of the species belonging to the Torpedinidae family are, indeed, classified as Data Deficient, so as, in most of the cases, no proper management measures are available for the conservation of these species. For this reason, the main goal of this study is to provide new information on life-history traits of three species inhabiting the Mediterranean Sea. Age and growth were estimated through direct annuli count of 146 vertebral centra sections of Torpedo marmorata. Females' growth pattern was found to be better described by a S-shaped function (Gompertz L∞ = 622mm TL; k = 0.15; IP=2.75 years), while males' by a logarithmic one (von Bertalanffy L∞ = 485mm TL; k = 0.14; t0 = -2.28). The oldest female and male were aged 17 (560mm TL) and 11 (432mm TL), respectively. Females (L50=379mm TL and A50=5.5 years) appeared to mature later than males (L50=272mm TL and A50=3.8 years), also attaining bigger sizes. Despite the observation of late-pregnant females being found only in autumn and regressing ones in autumn and winter, the presence of juveniles during the whole year may indicate a longer reproductive period. The stomach content analysis identified T. marmorata as a top predator (TROPH=4.38) with a very narrow trophic niche (Bi=0.22), extremely specialized in feeding on bony fishes. In addition, this work provides new and updated information on T. torpedo and the rare Tetronarce nobiliana growth, reproductive features and diet. Therefore, offering new essential data to assess the population conditions of all Torpedinidae species that inhabit the Mediterranean Sea, will lead to effective conservation plans.

Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum.

The functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber-stellate cell-Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency, but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

Living naked: first case of lack of skin-related structures in an elasmobranch, the blackmouth catshark (Galeus melastomus).

As far as is known, in this paper the first case of lacking of skin-related structures (epidermis, stratum laxum, dermal denticles and teeth) in a free-swimming elasmobranch, the blackmouth catshark, Galeus melastomus, is reported. The individual was caught by trawl in Sardinian waters (central-western Mediterranean) in July 2019 at a depth of 500 m. Although this kind of morphological abnormality is potentially fatal, the observations suggested that the specimen was in good health and well developed.

Quantitative Evaluation of Meniscal Healing Process of Degenerative Meniscus Lesions Treated with Hyaluronic Acid: A Clinical and MRI Study.

PURPOSE: We aimed to evaluate clinical efficacy and healing effects of conservative management of degenerative meniscus lesions (DMLs) with a hyaluronic acid (HA) hydrogel. METHODS: Patients were subjected to two HA injections two weeks apart. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Patient's Global Assessment (PtGA) and Clinical Observer Global Assessment (CoGA) of the disease were assessed at baseline, 30, and 60 days after treatment. Short Form (36) Health Survey (SF-36) was assessed at baseline and 60 days after treatment. One year after treatment, patients were called to know whether any of them had undergone arthroscopic partial meniscectomy (APM). All patients underwent magnetic resonance imaging using a 1.5-T Magnetic Resonance Imaging (MRI) scanner (Siemens Aera), which included a T2 mapping pulse sequence with multiple echoes at baseline and 60 days after treatment. RESULTS: 40 patients were enrolled. WOMAC score, physical function subscale, PtGA and CoGA, and SF-36 showed a statistically significant difference between baseline and follow-up. One year after treatment, only one patient had undergone APM. A decrease in the T2 measurement was detected in the posterior horn medial meniscus in 39% of cases in both the red and red-white zone, and in 60% of cases in the white zone; in the posterior horn lateral meniscus in 55% of cases in both the red and white zones, and in 65% of cases in the red-white zone. Only for the latter, there was a statistically significant difference between baseline and posttreatment T2 measurements. CONCLUSION: This study supports the use of HA in the conservative management of DML as it is clinically effective and enhances meniscus healing as demonstrated by T2 measurements. Moreover, it reduces the need for APM at 1-year follow-up.

Subtrocantheric nonunion following fracture of an arthrodesed hip: a case report.

In recent years in the era of successful of total hip replacement, hip arthrodesis is rarely performed. The anatomy and biomechanics of an arthrodesed hip is altered, thus influencing the treatments strategies in case of fracture or nonunions. This case report describes the management and therapeutic solution for the treatment of subtrochanteric nonunion in a patient with hip arthrodesis. Satisfactory outcomes were finally obtained after a double surgical procedure.

Efficacy and safety of viscosupplementation with hyaluronic acid for hip osteoarthritis: results from a cross-sectional study with a minimum follow-up of 4 years.

BACKGROUND AND AIM OF THE WORK: Osteoarthritis is the most common cause of disability in elderly. Hip osteoarthritis is the second most frequent form affecting a large joint and the social and economic impact on society of its related disability is expected to increase. The purpose of this study was to verify the efficacy and safety of ultrasound-guided viscosupplementation with high weight hyaluronic acid in hip osteoarthritis. METHODS: 183 patients with painful hip OA (Kellgren-Lawrence 1-2-3) were treated from January 2014 to December 2016 with viscosupplementation. Patients were evaluated before injection (T0) and after 1,2,3,4 years through the VAS scale and Harris Hip Score (HHS). Patients who underwent to subsequent injections were followed and assessed. Subjects who underwent prosthesis were analyzed for a minimum of 6 months in order to detect any early postoperative complication. RESULTS: The mean improvement of HHS and VAS between T0 and T1 was statistically significant. Patients who underwent subsequent injections showed a higher improvement even if statistical significance was not observed. Results showed that patients with grade 2 of osteoarthritis had the higher change in the scores. No adverse effects were registered. No early complications were reported in those patients who needed prosthesis. DISCUSSION AND CONCLUSIONS: Results observed confirm that ultrasound-guided viscosupplementation with high weight hyaluronic acid could be a possibility in the treatment of hip osteoarthritis, especially in patients with Kellgren-Lawrence grade 2 of disease. Subsequent injections are not characterized by similar positive effects. Outcomes of prosthetic surgery are not influenced by viscosupplementation.

Demographic and clinical differences between ankylosing spondylitis and non-radiographic axial spondyloarthritis: results from a multicentre retrospective study in the Lazio region of Italy.

OBJECTIVES: Axial spondyloarthritides (axSpA) are a group of disorders that share similar pathogenetic mechanisms and clinical picture. The aim of this retrospective multicentric study was to evaluate demographic and clinical differences between ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) patients. METHODS: Patients from 7 rheumatological centres in the Lazio region of Italy were included from January 1st, 2010 to April 1st, 2018, if they had undergone pelvic and/or spine radiographs or magnetic resonance imaging (MRI). Images were evaluated by one experienced radiologist in each centre who already had the clinical suspicion of axSpA. Clinical and therapeutic data were collected at the last observation visit. Categorical variables were presented with percentages and analysed by Chi squared test. Continuous variables were expressed as mean ± standard deviation and compared using the parametric unpaired t-test or the non-parametric Mann-Whitney U-test, when appropriate. p-values <0.05 were considered significant. RESULTS: 210 axSpA patients were included: 65.2% with AS and 34.7% with nr-axSpA. When comparing the two groups, AS patients had longer disease duration, were older, were more frequently males, had a greater diagnostic delay and a higher body mass index than the nr-axSpA patients (p<0.0001, p<0.0001, p=0.003 p=0.007, and p=0.04, respectively). The peripheral joints of the nr-axSpA patients were more frequently involved, had higher frequency of inflammatory bowel disease, higher C-reactive protein levels and lower frequency of HLA-B27 positivity (p=0.005, p=0.007, p=0.01, and p=0.01, respectively). TNF inhibitors were used in 87.8% patients with AS and 78.3% with nr-axSpA (p=0.04). More fat metaplasia was observed on MRI in the nr-axSpA group than in the AS group at sacroiliac joints (p=0.003), and more backfills were detected in the AS group on spine-MRI (p=0.003). Spine-bone marrow oedema was more prevalent in AS than in nr-axSpA (p=0.04), and more sclerosis and backfill were found in AS (p=0.003 and p=0.01, respectively). CONCLUSIONS: In clinical practice, distinctive features in AS and nr-axSpA patients emerged. Imaging is crucial in guiding the choice of treatment in order to control disease activity and inflammation.

Bone and lymph node metastases from occult mammary carcinoma: a case report of carcinoma of unknown primary (CUP) Syndrome.

Cancer of unknown provenance is a rare disease, accounting approximately for up to 1% of all breast cancers. A 68-year-old female was admitted to the Medical Oncology Unit of Policlinico Universitario G.Martino because of diffused bone-involvement, with mixed (osteolytic/osteoblastic) features, which interested almost every skeletal structure of the body (vertebral bodies of the entire column, costal skeleton, sternum, proximal third of both humeri, scapulae, clavicles, pelvis and femurs), suspicious for metastatic disease.

Spontaneous reduction of a minimally complex cyst mimicking a renal cancer.

Renal cyst shrinkage is a rare finding. Since the collapsed cystic walls may mimic soft tissue components, this scenario has to be taken into account in the differential diagnosis of benign and malignant renal cysts.