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Leiomyomas are smooth muscle-derived benign neoplasms that can affect all organs, most frequently in the uterus. Fumarate hydratase gene (FH) mutation is characterised by an autosomal dominant disease with increased occurrence of renal tumours, but also by cutaneous (CLs) and uterine leiomyomas (ULs). So far, an increased occurrence of skin tumours in non-mutated patients with ULs has not been verified. To this aim, a case-group of women who were FH non-mutated patients surgically treated for ULs (n = 34) was compared with a control-group (n = 37) of consecutive age-matched healthy women. The occurrence of skin neoplasms, including CLs and dermatofibromas (DFs), was evaluated. Moreover, the microscopic features of FH non-mutated skin tumours were compared with those of an age-matched population group (n = 70) who presented, in their clinical history, only one type of skin tumour and no ULs. Immunohistochemical and in vitro studies analysed TGFβ and vitamin D receptor expression. FH non-mutated patients with ULs displayed a higher occurrence of CLs and DFs (p < 0.03 and p < 0.001), but not of other types of skin tumours. Immunohistochemistry revealed a lower vitamin D receptor (VDR) expression in CLs and DFs from the ULs group compared with those from the population group (p < 0.01), but a similar distribution of TGFβ-receptors and SMAD3. In vitro studies documented that TGFβ-1 treatment and vitamin D3 have opposite effects on α-SMA, TGFβR2 and VDR expression on dermal fibroblast and leiomyoma cell cultures. This unreported increased occurrence of CLs and DFs in FH non-mutated patients with symptomatic ULs with vitamin D deficiency suggests a potential pathogenetic role of vitamin D bioavailability also for CLs and DFs.

This essay explores the character of Cerulia in Frances Burney’s dramatic play, Hubert de Vere, composed and revised in the 1790s, yet never published or staged in Burney’s lifetime. Cerulia seems to eschew any easy dramatic categorization, as she cannot be identified with the heroine of the play. Undeniably, she is a victim, but of whom/what, we may wonder? Does attempting to define the nature of the hamartia of which Cerulia remains victim lead the “ideal” reader/viewer toward either fate/the gods or, rather, social apparatuses? And, finally, what about the eponymous protagonist Hubert de Vere? Is it correct to identify de Vere as the actant “hero”, or perhaps as per the sub-category “villain hero” so popular in late eighteenth-century dramas? Burney’s adroit exploitation of tropology and literary allusion in Hubert de Vere will be at the centre of this essay. In particular, I will examine the last act of the play, where the themes of confinement, imprisonment, and escape take on tragic hues. Though unpublished until 1995, these scenes are among the most vivid and, indeed, the most shocking Burney ever wrote. It is my contention that a long overdue appraisal of female characterisation in Hubert de Vere can shed novel light –at once both disturbing and liberating– on Frances Burney’s oeuvre at large.

Background: Femoroacetabular impingement (FAI) is common. The present systematic review updates the current evidence on return to sport (RTS) in patients who have undergone arthroscopic surgery for FAI in any of its variants (CAM, pincer, or both). Methods: The outcomes of interest were sports-related patient-reported outcome measures (PROMs) and the level and time to RTS. All available clinical studies concerning the RTS following arthroscopic management of FAI were considered. In July 2024, the following databases were accessed following the PRISMA guidelines: Embase, Web of Science, and PubMed. Only studies with a minimum of six months of follow-up were eligible. Results: From 1245 initially identified articles, 43 studies (4103 patients) met the inclusion criteria, in which 32.1% (1317 of 4103 patients) were women. The mean length of follow-up was 33.7 ± 15.8 months. The mean age was 28.1 ± 7.2 years, the mean BMI was 24.7 ± 6.4 kg/m2, and 79.6% ± 27.8% of patients returned to sport at the same or higher level at a mean of 14.3 ± 9.6 months. The mean time away from sports was 8.0 ± 3.3 months. Conclusion: Arthroscopic management for FAI leads to a high rate of RTS, with approximately 80% of patients returning to their preinjury level. Future research should focus on standardised definitions of RTS, sport-specific rehabilitation protocols, and the influence of deformity and procedures on RTS. [ABSTRACT FROM AUTHOR]

Teresa Paolucci,1 Letizia Pezzi,1 Roberta La Verde,2 Pasqualino Maietta Latessa,3 Rosa grazia Bellomo,4 Raoul Saggini1 1University G. d’Annunzio Chieti, Department of Medical and Oral Sciences and Biotechnologies, Chieti-Pescara, Italy; 2S. Filippo Neri Hospital, Physical Medicine and Rehabilitation, “Sapienza” University, Rome, Italy; 3Department for Life Quality Studies, University of Bologna, Bologna, Italy; 4University of Study of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, ItalyCorrespondence: Teresa PaolucciG. D’Annunzio University of Chieti-Pescara, Rehabilitation Unit, Department of Medical and Oral Sciences and Biotechnologies (DSMOB), Via Dei Vestini 66100, Chieti Scalo, ItalyEmail teresapaolucci@hotmail.comBackground: Aging has been associated with the progressive depletion of lean mass, reductions in muscle strength and the coordination of the lower extremities, accompanied by decreased gait assurance and balance control. Also, less balance control favors falling which is the leading cause of injury among the elderly. The aim of this systematic review is to identify and evaluate existing evidence regarding the use of focused vibration (FV) to improve balance and reduce the risk of falling during the rehabilitation of elderly populations.Methods: The PICO question is what are the effects of focal/segmental/local vibration training on the assessment of balance and the risk of falls among the elderly population? A thorough literature review was conducted between May 1, 2009, and June 30, 2019, for studies in English, randomized clinical trials, including crossover and prospective design studies with assessing balance and the risk of falls in elderly populations (age > 60 years).Results: Eight articles (N = 8) satisfied the inclusion criteria and were considered, of which 6 are RTC, one cross-sectional study and one clinical study, for a total of 635 participants. A total of 6 different vibration devices were used, each of which was associated with different FV frequency and amplitude characteristics and different treatment protocols.Conclusion: In conclusion, FV can be effective in decreasing the risk of falls and improving the assessment of balance, but more evidence is necessary considering the limits of the studies; however, it does look an important promise during rehabilitative treatment.Keywords: rehabilitation, risk of falls, exercise, vibration, equilibrium

Abstract In this study we used a combination of measures including regional cerebral blood flow (rCBF) and heart rate variability (HRV) to investigate brain–heart correlates of longitudinal baseline changes of chronic low back pain (cLBP) after osteopathic manipulative treatment (OMT). Thirty-two right-handed patients were randomised and divided into 4 weekly session of OMT (N = 16) or Sham (N = 16). Participants aged 42.3 ± 7.3 (M/F: 20/12) with cLBP (duration: 14.6 ± 8.0 m). At the end of the study, patients receiving OMT showed decreased baseline rCBF within several regions belonging to the pain matrix (left posterior insula, left anterior cingulate cortex, left thalamus), sensory regions (left superior parietal lobe), middle frontal lobe and left cuneus. Conversely, rCBF was increased in right anterior insula, bilateral striatum, left posterior cingulate cortex, right prefrontal cortex, left cerebellum and right ventroposterior lateral thalamus in the OMT group as compared with Sham. OMT showed a statistically significant negative correlation between baseline High Frequency HRV changes and rCBF changes at T2 in the left posterior insula and bilateral lentiform nucleus. The same brain regions showed a positive correlation between rCBF changes and Low Frequency HRV baseline changes at T2. These findings suggest that OMT can play a significant role in regulating brain–heart interaction mechanisms.

Objective To determine whether asymptomatic flexible flat feet show specific postural assessment with respect to neutral feet in 6-year-old children. Methods In this cross-sectional observational study, 164 subjects were observed and divided into two groups: 57 with flexible flat feet and 107 with neutral feet. A non-quantitative inspection by podoscopy and baropodometry were performed to evaluate plantar support, and a clinical examination to assess postural setting. Results The prevalence of flexible flat feet was 34.8%. The differenceinthe mean centre of pressure (CoP) between the two groups was significant (p=0.028), regarding the antero-posterior direction of CoP only. There was no significant differencein the presence of postural growth disharmony between the neutral and flat-feet groups. Conclusion The flattening of the plantar archseems to be linked to a displacement of CoP Y, more posterior in flat feet than in neutral feet; on the other hand, postural harmony in 6-year-old children during growth is not influenced by flat feet.

Teresa Paolucci,1 Letizia Pezzi,1 Antonello Marco Centra,1 Niki Giannandrea,1 Rosa Grazia Bellomo,2 Raoul Saggini1 1Department of Medical Oral Sciences and Biotechnology (DiSmob), Physical Medicine and Rehabilitation Unit, G. D’Annunzio University of Chieti-Pescara, Chieti, Italy; 2Department of Biomolecular Sciences, University of Study of Urbino Carlo Bo, Urbino, ItalyCorrespondence: Teresa PaolucciG. D’Annunzio University of Chieti-Pescara, Chieti, ItalyEmail teresapaolucci@hotmail.comAbstract: Electromagnetic fields (EMFs) provide a non-invasive, safe, and easy method to treat pain with respect to musculoskeletal diseases. The purpose of this systematic review was to describe the use of electromagnetic therapy in the rehabilitation field by investigating the efficacy in acute and chronic pain in the musculoskeletal disorders. A database search was conducted using the following resources: PubMed, Cochrane, PEDro, SCOPUS, and WoS. The following MESH terms were used: [Electromagnetic field AND/OR Rehabilitation], [Electromagnetic field AND/OR Pain], [Pulsed Magnetic field AND/OR Rehabilitation] and [Pulsed Magnetic field AND/OR Pain], [Pulsed Electromagnetic field AND/OR Rehabilitation] and [Pulsed Electromagnetic field AND/OR Pain], per the guidelines of the PRISMA statement. Articles published between January 1, 2009 and December 31, 2018 were included as assessment of musculoskeletal pain conditions, randomized clinical trial including crossover and prospective design studies, full English text available, population age > 18 years; instead were excluded neurological randomized clinical trials, transcranial magnetic stimulation application, neuropathic pain, animal/in vitro studies, and articles without English abstract or English full text. Three independent investigators (AMC, NG, and LP) retrieved all the information. Twenty-one RTC (N=21) were considered for the inclusion and exclusion criteria. The results showed as pulsed magnetic fields at low intensity and frequency (from 1 Hz up to 100 Hz) are commonly used with efficacy in resolving musculoskeletal pain. EMFs therapy is a well tolerated, effective with no negative side effects, which can be integrated with rehabilitation for the treatment of chronic and acute pain in musculoskeletal diseases, but further studies are needed to examine the use of more standardized protocols.Keywords: pulsed electromagnetic fields, rehabilitation, physical medicine, magnetic therapy, pain

Rosa Grazia Bellomo,1,* Teresa Paolucci,2,* Niki Giannandrea,2 Letizia Pezzi,2 Raoul Saggini2 1University of Study of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, Italy; 2University G.d’Annunzio Chieti, Physical Medicine and Rehabilitation, Department of Medical and Oral Sciences and Biotechnologies (DSMOB), Chieti-Pescara, Italy*These authors contributed equally to this workCorrespondence: Teresa PaolucciUniversity G.d’Annunzio Chieti, Department of Medical and Oral Sciences and Biotechnologies, Viale Abruzzo 322, Chieti-Pescara 66100 CH, ItalyEmail teresapaolucci@hotmail.comPurpose: Facet joint syndrome (FJS) is an arthritis-like condition of the spine that can be a significant source of low back pain (LBP). Ozone therapy (OT) could be an additional treatment method. We evaluated the therapeutic results of percutaneous injection of ozone to ablate acute LBP caused by FJS.Methods: A 73-year-old Caucasian woman was treated by OT: one ozone injection (20 μg/mL) per week for 3 weeks under ultrasound guidance. After a break of 1 week, she performed exercises for aquatic rehabilitation (twice a week for 4 weeks).Results: The outcome measure was pain relief for ≥ 6 months according to the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory (BPI) test. From baseline to 1 month after OT, a reduction in pain was documented and the result was maintained at 6-month follow-up.Conclusion: OT followed by aquatic exercises could be efficacious against the LBP caused by FJS.Keywords: ozone, low back pain, Oswestry Disability Index, spine, injection

Background Fibromyalgia is a chronic pain syndrome which occurs in the absence of an organic damage, whom causes is still unclear. Aims of this pilot study were to investigate the neural correlates of fibromyalgia in response to pain-related visual stimuli and explore the psychological differences among fibromyalgia, chronic low back pain (CLBP) and healthy conditions. Methods After a clinical assessment, electrophysiological responses to pain-related visual stimuli were recorded using a 256-Hydrocel Geodesic-Sensor-Net. Event-related potentials (ERPs), standardised low-resolution electromagnetic tomography (sLORETA), and psychological (Symptom Checklist-90-Revised) data were analysed for a total sample of 23 women (5 healthy volunteers, 12 fibromyalgia patients, 6 CLBP patients). Results The main finding was that fibromyalgia women reported a different brain response to pain-related visual stimuli on the frontal montage compared to women with CLBP ( p = .028). Moreover, fibromyalgia women showed an increased activity mainly on the hippocampus ( p = .003) and the posterior cingulate cortex ( p ≤ .001) in response to algic stimuli compared to not algic ones. Lastly, these women presented higher scores on the somatization ( p = .002), obsession-compulsion ( p = .045), depression ( p = .043) and positive symptom distress ( p = .023) dimensions compared to the healthy women. Conclusions These preliminary results suggest that although the painful symptoms are similar, the central elaboration of pain could be different between women with fibromyalgia and those with CLBP. Moreover, these findings provide preliminary evidences about the great alert and the central sensitivity to pain-related information regarding fibromyalgia patients.

Background: Onychomycosis numbers among the most common fungal infections in humans affecting finger- or toenails. Histology remains a frequently applied screening technique to diagnose onychomycosis. Screening slides for fungal elements can be time-consuming for pathologists, and sensitivity in cases with low amounts of fungi remains a concern. Convolutional neural networks (CNNs) have revolutionized image classification in recent years. The goal of our project was to evaluate if a U-NET-based segmentation approach as a subcategory of CNNs can be applied to detect fungal elements on digitized histologic sections of human nail specimens and to compare it with the performance of 11 board-certified dermatopathologists. Methods: In total, 664 corresponding H&E- and PAS-stained histologic whole-slide images (WSIs) of human nail plates from four different laboratories were digitized. Histologic structures were manually annotated. A U-NET image segmentation model was trained for binary segmentation on the dataset generated by annotated slides. Results: The U-NET algorithm detected 90.5% of WSIs with fungi, demonstrating a comparable sensitivity with that of the 11 board-certified dermatopathologists (sensitivity of 89.2%). Conclusions: Our results demonstrate that machine-learning-based algorithms applied to real-world clinical cases can produce comparable sensitivities to human pathologists. Our established U-NET may be used as a supportive diagnostic tool to preselect possible slides with fungal elements. Slides where fungal elements are indicated by our U-NET should be reevaluated by the pathologist to confirm or refute the diagnosis of onychomycosis.

Fatigue is a multidimensional symptom with both physical and cognitive aspects, which can affect the quality of daily and working life activities. Motor Imagery (MI) represents an important resource for use during the rehabilitation processes, useful, among others, for job integration/reintegration, of neurological pathologies, such as Multiple Sclerosis (MS). To define the effective rehabilitation protocols that integrate MI for the reduction of fatigue in patients with MS (PwMS), a literary review was performed through August 2020. Five articles were included in the qualitative synthesis, including two feasibility pilot randomized control trials (RCTs) and 3 RCTs with good quality according to the PEDro score and a low risk of bias according to the Cochrane Collaboration tool. The literature suggested that MI, in association with rhythmic-auditory cues, may be an effective rehabilitation resource for reducing fatigue. Positive effects were observed on perceived cognitive and psychological fatigue. PwMS require greater compensatory strategies than healthy individuals, and the use of rhythmic-auditory cues may be useful for optimizing the cognitive processing of MI, which acts as an internal stimulus that is enhanced and made more vivid by outside cues. These findings provide evidence that MI is a promising rehabilitation tool for reducing fatigue in PwMS and return to work strategies.

Schwannomas are benign, encapsulated nerve sheath tumors arising from Schwann cells; several histologic variants of schwannoma have been described, including the exceedingly rare glandular schwannoma (GS). The histogenesis of the glands in GS (as well as in other peripheral nerve sheath tumors with a glandular component) remains unclear; no consensus exists as to whether glands should be interpreted as metaplastic elements or entrapped reactive glands. We report a case of GS with detailed immunohistochemical analysis of the epithelial component. We believe that our findings raise further questions regarding the histogenesis of glands in GS, casting doubts on the traditional distinction between true metaplasia and glandular entrapment. Further research is warranted in this regard.

T Paolucci,1 RG Bellomo,2 MA Centra,1 N Giannandrea,1 L Pezzi,1 R Saggini11University G.d’Annunzio Chieti, Department of Medical and Oral Sciences and Biotechnologies, Chieti-Pescara, Italy; 2University of Study of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, ItalyBackground: Mesotherapy can be included as an ancillary treatment in the management of localized pain in rehabilitation, but there are no definitive treatment protocols for this approach.Objectives: The purpose of this review was to examine new indications for more standard protocols of mesotherapy in rehabilitation.Materials and methods: This systematic review was performed using the following resources: PubMed, Cochrane, PEDro, Scopus, and Google Scholar. The following algorithm was developed, based on the PICO acronym, to evaluate the effects of mesotherapy, with pain as the primary outcome (MESH terms): [mesotherapy AND pain], [mesotherapy AND musculoskeletal], [mesotherapy AND musculoskeletal disorder], [intradermal therapy AND pain], and [intradermal therapy AND musculoskeletal disorder].Results: Seven articles (N=7) satisfied the inclusion criteria and were considered in the review: two of them treated osteoarthritis of the knee (3 sessions) and pes anserine (9 sessions) emphasizing a good efficacy of mesotherapy. Five studies analyzed spine diseases (specifically, two was about chronic and nonspecific neck pain, two about acute low back pain and one about chronic spinal pain): the results of mesotherapy treatment are encouraging both for the resolution of acute and chronic musculoskeletal vertebral pain from one to five sessions.Conclusion: Mesotherapy showed a good effect to reduce acute and chronic musculoskeletal pain and, also, it is a well-tolerated treatment. Nonetheless future randomized controlled trials should be desirable for more uniform treatment protocols.Keywords: mesotherapy, intradermal injection, rehabilitation, pain, musculoskeletal

Skeletal muscle consists of long plurinucleate and contractile structures, able to regenerate and repair tissue damage by their resident stem cells: satellite cells (SCs). Reduced skeletal muscle regeneration and progressive atrophy are typical features of sarcopenia, which has important health care implications for humans. Sarcopenia treatment is usually based on physical exercise and nutritional plans, possibly associated with rehabilitation programs, such as vibratory stimulation. Vibrations stimulate muscles and can increase postural stability, balance, and walking in aged and sarcopenic patients. However, the possible direct effect of vibration on SCs is still unclear. Here, we show the effects of focused vibrations administered at increasing time intervals on SCs, isolated from young and aged subjects and cultured in vitro. After stimulations, we found in both young and aged subjects a reduced percentage of apoptotic cells, increased cell size and percentage of aligned cells, mitotic events, and activated cells. We also found an increased number of cells only in young samples. Our results highlight for the first time the presence of direct effects of mechanical vibrations on human SCs. These effects seem to be age-dependent, consisting of a proliferative response of cells derived from young subjects vs. a differentiative response of cells from aged subjects.

Objective To examine the pain-reducing effects of intra-articular oxygen–ozone (O 2 O 3 ) injections and mechanical focal vibration (mFV) versus O 2 O 3 injections alone in patients with knee osteoarthritis. Methods Patients with chronic pain (>6 weeks) due to knee osteoarthritis (II–III on the Kellgren–Lawrence scale) were consecutively enrolled and divided into two groups: O 2 O 3 (n = 25) and O 2 O 3 -mFV (n = 24). The visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Medical Research Council (MRC) Manual Muscle Testing scale were administered at baseline (before treatment), after 3 weeks of treatment, and 1 month after the end of treatment. Patients received three once-weekly intra-articular injections of O 2 O 3 into the knee (20 mL O 3 , 20 μg/mL). The O 2 O 3 -mFV group also underwent nine sessions of mFV (three sessions per week). Results The VAS score, KOOS, and MRC score were significantly better in the O 2 O 3 -mFV than O 2 O 3 group. The within-group analysis showed that all scores improved over time compared with baseline and were maintained even 1 month after treatment. No adverse events occurred. Conclusion An integrated rehabilitation protocol involving O 2 O 3 injections and mFV for 3 weeks reduces pain, increases autonomy in daily life activities, and strengthens the quadriceps femoris.

Background: Telerehabilitation (TR) in chronic stroke patients has emerged as a promising modality to deliver rehabilitative treatment-at-home. The primary objective of our methodical clinical study was to determine the efficacy of a novel rehabilitative device in terms of recovery of function in daily activities and patient satisfaction and acceptance of the medical device provided. Methods: A 12-week physiotherapy program (balance exercises, upper and lower limb exercises with specific motor tasks using a biofeedback system and exergaming) was administered using the WeReha device. Twenty-five ( N = 25) chronic stroke outpatients were enrolled, and the data of 22 patients was analyzed. Clinical data and functional parameters were collected by Berg Balance scale (BBS), Barthel Index (BI), Fugl-Meyer scale (FM), Modified Rankin scale (mRS), and Technology Acceptance Model (TAM) questionnaire at baseline (T0), after treatment (T1), and at the 12-week follow-up (T2). Statistical tests were used to detect significant differences ( P