GATA3 and TGF-ß in normal placenta and pre-eclampsia.

GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-ß signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-ß in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-ß was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-ß and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.

Executive Functions Assessment Based on Wireless EEG and 3D Gait Analysis During Dual-Task: A Feasibility Study.

Executive functions (EFs) are neurocognitive processes planning and regulating daily life actions. Performance of two simultaneous tasks, requiring the same cognitive resources, lead to a cognitive fatigue. Several studies investigated cognitive-motor task and the interference during walking, highlighting an increasing risk of falls especially in elderly and people with neurological diseases. A few studies instrumentally explored relationship between activation-no-activation of two EFs (working memory and inhibition) and spatial-temporal gait parameters. Aim of our study was to detect activation of inhibition and working memory during progressive difficulty levels of cognitive tasks and spontaneous walking using, respectively, wireless electroencephalography (EEG) and 3D-gait analysis. Thirteen healthy subjects were recruited. Two cognitive tasks were performed, activating inhibition (Go-NoGo) and working memory (N-back). EEG features (absolute and relative power in different bands) and kinematic parameters (7 spatial-temporal ones and Gait Variable Score for 9 range of motion of lower limbs) were analyzed. A significant decrease of stride length and an increase of external-rotation of foot progression were found during dual task with Go-NoGo. Moreover, a significant correlation was found between the relative power in the delta band at channels Fz, C4 and progressive difficulty levels of Go-NoGo (activating inhibition) during walking, whereas working memory showed no correlation. This study reinforces the hypothesis of the prevalent involvement of inhibition with respect to working memory during dual task walking and reveals specific kinematic adaptations. The foundations for EEG-based monitoring of cognitive processes involved in gait are laid. Clinical and Translational Impact Statement: Clinical and instrumental evaluation and training of executive functions (as inhibition), during cognitive-motor task, could be useful for rehabilitation treatment of gait disorder in elderly and people with neurological disease.

Lateral Pectoral Nerve Identification through Ultrasound-Guided Methylene Blue Injection during Selective Peripheral Neurectomy for Shoulder Spasticity: Proposal for a New Procedure.

Internally rotated and adducted shoulder is a common posture in upper limb spasticity. Selective peripheral neurectomy is a useful and viable surgical technique to ameliorate spasticity, and the lateral pectoral nerve (LPN) could be a potential good target to manage shoulder spasticity presenting with internal rotation. However, there are some limitations related to this procedure, such as potential anatomical variability and the necessity of intraoperative surgical exploration to identify the target nerve requiring wide surgical incisions. This could result in higher post-surgical discomfort for the patient. Therefore, the aim of our study was to describe a modification of the traditional selective peripheral neurectomy procedure of the LPN through the perioperative ultrasound-guided marking of the target nerve with methylene blue. The details of the localization and marking procedure are described, as well as the surgical technique of peripheral selective neurectomy and the potential advantages in terms of nerve localization, surgical precision and patients' post-surgical discomfort. We suggest that the proposed modified procedure could be a valid technique to address some current limitations and move the surgical treatment of spasticity toward increasingly tailored management due to the ease of nerve identification, the possibility of handling potential anatomical variability and the resulting smaller surgical incisions.

Acute Foot Drop Caused by Intraneural Ganglion Cyst of the Peroneal Nerve: Literature Review and Case Report.

BACKGROUND: Foot drop (FD) is characterized by an inability to lift the foot against gravity because of dorsiflexor muscle weakness. The aim of the present study is to report a clinical case of acute non-traumatic FD in patients with peroneal intraneural ganglion, after performing a scoping review on the methodological management of this disease. METHODS: We performed a review of the literature and reported the case of a 49-year-old man with acute FD caused by an intraneural ganglion cyst of the peroneal nerve. RESULTS: Out of a total of 201 articles, 3 were suitable for our review beyond our case report. The acute FD caused by peroneal intraneural ganglion can be managed by a careful clinical-instrumental differential diagnosis. A targeted surgery with subsequent rehabilitation produced a satisfactory motor recovery. CONCLUSIONS: Acute FD requires an appropriate diagnostic-therapeutic framework to identify and effectively treat the causes in order to promote complete recovery.

Sagittal kinematics and imbalance of the spine and whole body during walking in late-onset Pompe disease.

Late-onset Pompe disease (LOPD) is characterized by postural abnormalities mainly due to involvement of paraspinal lumbar and abdominal-pelvic muscles. Previous studies quantitatively analyzed static upright posture, spatial-temporal parameters, and kinematics of the lower limbs and trunk, considered as single bone segment. Sagittal plane analysis of the spine and whole body during walking has never been investigated in patients with LOPD. The aim of the study was to evaluate sagittal kinematics and imbalance of the spine and whole body in patients with LOPD by three-dimensional (3-D)-motion analysis using an appropriate marker set protocol and introducing innovative kinematic parameters. Seven siblings with LOPD were assessed by 3-D-stereophotogrammetry using the DB-total protocol, which allows to analyze sagittal alignment of whole body. Fourteen age- and sex-matched healthy subjects were used as controls. LOPD group showed a flattening of the spinal curvatures, with a head and neck posteriorization with respect to sacrum, a significant increase of concavity in Heel-S2-Nasion/C7 angles, a rear-position of upper limbs with respect to pelvis, a shorter pendular activity, and a trend of elbow extension during ambulation. Moreover, a significant increase of excursion range in most of sagittal parameters was found. The present study highlighted a specific pathological postural pattern, resembling "man falling backwards," which reveals a biomechanical compensation strategy of patients with LOPD to maintain the balance against the instability of the spinopelvic region, kinematically verified by increase of the excursion ranges. DB-total kinematic parameters might be useful for functional evaluation and for monitoring response to enzyme replacement therapy, rehabilitation project, and disease progression.NEW & NOTEWORTHY This study is the first to quantitatively characterize the sagittal spine and whole body posture of patients with late-onset Pompe disease during walking, showing a pathological kinematic pattern defined "man falling backwards." 3-D-motion analysis, with a specific marker set (DB-total protocol) introducing new whole body kinematic parameters, may be useful for accurate functional evaluation and monitoring this rare disease.

Long-Term Spasticity Management in Post-Stroke Patients: Issues and Possible Actions-A Systematic Review with an Italian Expert Opinion.

Spasticity is a well-known motor dysfunction occurring after a stroke. A group of Italian physicians' experts in treating post-stroke spasticity (PSS) reviewed the current scientific evidence concerning the state-of-the-art clinical management of PSS management and the appropriate use of botulinum toxin, aiming to identify issues, possible actions, and effective management of the patient affected by spasticity. The participants were clinicians specifically selected to cover the range of multidisciplinary clinical and research expertise needed to diagnose and manage PSS. When evidence was not available, the panel discussed and agreed on the best way to manage and treat PSS. To address the barriers identified, the panel provides a series of consensus recommendations. This systematic review provides a focused guide in the evaluation and management of patients with PSS and its complications. The recommendations reached by this panel of experts should be used by less-experienced doctors in real life and should be used as a guide on how to best use botulinum toxin injection in treating spasticity after a stroke.

Antiinflammatory Activities of Curcumin and Spirulina: Focus on Their Role against COVID-19.

Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.

SARS-CoV-2 Infection: A Clinical and Histopathological Study in Pregnancy.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model.

OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens. DESIGN: In-vitro model of adipogenesis. METHODS: We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARÉ£ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment. RESULTS: Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF. CONCLUSION: Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.

Transient Receptor Potential (TRP) Channels in Tumor Vascularization.

Tumor diseases are unfortunately quick spreading, even though numerous studies are under way to improve early diagnosis and targeted treatments that take into account both the different characteristics associated with the various tumor types and the conditions of individual patients. In recent years, studies have focused on the role of ion channels in tumor development, as these proteins are involved in several cellular processes relevant to neoplastic transformation. Among all ion channels, many studies have focused on the superfamily of Transient Receptor Potential (TRP) channels, which are non-selective cation channels mediating extracellular Ca2+ influx. In this review, we examined the role of different endothelial TRP channel isoforms in tumor vessel formation, a process that is essential in tumor growth and metastasis.

Mobile-Bearing Total Ankle Replacement In Vivo Kinematic Assessment: A Prospective Study Protocol.

Total ankle prosthesis as a surgical solution in the case of end-stage osteoarthritis has seen a considerable increase in the last two decades. This study protocol arises from the need to understand the in vivo kinematics of mobile-bearing, flat tibial component total ankle replacement, evaluating the real range of motion and the reciprocal relationships between the components during normal motor tasks through the use of model-based radio-stereometric analysis (MB-RSA). In addition, pre- and post-operative evaluation of walking kinematics with inertial motion sensors, proprioception through a dedicated workstation, and clinical outcomes are discussed. We expect that based on our study protocol researchers will be able to improve future prosthetic designs and validate the setup of MB-RSA, as well as to understand "how an ankle prosthesis moves" once implanted in the patient.

Kinematic Evaluation of the Sagittal Posture during Walking in Healthy Subjects by 3D Motion Analysis Using DB-Total Protocol.

Posture can be evaluated by clinical and instrumental methods. Three-dimensional motion analysis is the gold standard for the static and dynamic postural assessment. Conventional stereophotogrammetric protocols are used to assess the posture of pelvis, hip, knee, ankle, trunk (considered as a single segment) and rarely head and upper limbs during walking. A few studies also analyzed the multi-segmental trunk and whole-body kinematics. Aim of our study was to evaluate the sagittal spine and the whole-body during walking in healthy subjects by 3D motion analysis using a new marker set. Fourteen healthy subjects were assessed by 3D-Stereophotogrammetry using the DB-Total protocol. Excursion Range, Absolute Excursion Range, Average, intra-subject Coefficient of Variation (CV) and inter-subject Standard Deviation Average (SD Average) of eighteen new kinematic parameters related to sagittal spine and whole-body posture were calculated. The analysis of the DB-Total parameters showed a high intra-subject (CV < 50%) and a high inter-subject (SD Average < 1) repeatability for the most of them. Kinematic curves and new additional values were reported. The present study introduced new postural values characterizing the sagittal spinal and whole-body alignment of healthy subjects during walking. DB-Total parameters may be useful for understanding multi-segmental body biomechanics and as a benchmark for pathological patterns.

Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent NF1 Gene Variants and Correlations with Neurocognitive Phenotype.

Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the NF1. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases). Clinical data were collected at the time of the mutation analysis and reviewed for accuracy in this investigation. An internal phenotypic categorization was applied. The 94% of the patients enrolled showed a severe phenotype with at least one systemic complication and a wide range of associated malignancies. Spine deformities were the most common complications in this cohort. We also reported 66 different NF1 mutations, of which 7 are novel mutations. Correlation analysis identified a slight significant inverse correlation between age at diagnosis and delayed acquisition of psychomotor skills with residual multi-domain cognitive impairment. Odds ratio with 95% confidence interval showed a higher prevalence of learning disabilities in patients carrying frameshift mutations. Overall, our results aim to offer an interesting contribution to studies on the genotype-phenotype of NF1 and in genetic management and counselling.

Nociplastic Pain in Multiple Sclerosis Spasticity: Dermatomal Evaluation, Treatment with Intradermal Saline Injection and Outcomes Assessed by 3D Gait Analysis: Review and a Case Report.

Nociplastic pain has been introduced by the IASP as a third category of pain, distinct from nociceptive and neuropathic pain. Pathogenetically, it is considered to be a continuum of these two types of pain after becoming chronic. Repetitive peripheral painful stimulation causes a central sensitization with hypersensitivity of the corresponding spinal metamer or brain region. Therefore, signs of altered nociception, such as allodynia, may be found on the tissues of the related dermatome, myotome and sclerotome, and characterize nociplastic pain. This kind of pain was found in over 20% of people with multiple sclerosis (pwMS), a demyelinating autoimmune disease that affects the central nervous system. Nociplastic pain may be an amplifier of spasticity, the main pyramidal symptom that affects about 80% of pwMS. This article details the case of a 36-year-old woman with multiple sclerosis who was affected by spasticity and non-specific pain of the lower limbs, disabling on walking. Previous analgesic and muscle relaxant treatment had no benefits. The diagnosis of nociplastic pain on the cutaneous tissue of the anterolateral region of the left thigh and its treatment with intradermal normal saline injection on the painful skin area showed immediate and lasting effects on pain and spasticity, improving significantly the patient's balance and walking, as assessed by a 3D motion analysis and rating scales.

Enhanced recovery (fast-track surgery) after total ankle replacement: The state of the art.

The post-operative results of a total ankle replacement are not determined solely by an optimal surgical technique, but by an appropriate anesthesiological and rehabilitative post-operative approach. Enhanced functional recovery often depends on a multidisciplinary approach based on a correct framework of the patient and his needs, requests, and characteristics. Extensive bibliographical research has been performed on Pubmed, Google Scholar, Scopus. This comprehensive and inclusive review of the literature aims to examine the state of the art of "fast-track" protocols employed in total ankle replacement (TAR), considering pre-operative preparation, anesthetic management, intraoperative and surgical factors, post-operative rehabilitative care and reduction of hospitalization time.

Physical decline and cognitive impairment in frail hypertensive elders during COVID-19.

BACKGROUND: Hypertension is common in older adults and its incidence increases with age. We investigated the correlation between physical and cognitive impairment in older adults with frailty and hypertension. METHODS: We recruited frail hypertensive older adults during the COVID-19 pandemic, between March 2021 and December 2021. Global cognitive function was assessed through the Montreal Cognitive Assessment (MoCA), physical frailty assessment was performed following the Fried criteria, and all patients underwent physical evaluation through 5-meter gait speed test. RESULTS: We enrolled 203 frail hypertensive older adults and we found a significant correlation between MoCA score and gait speed test (r: 0.495; p<0.001) in our population. To evaluate the impact of comorbidities and other factors on our results, we applied a linear regression analysis with MoCA score as a dependent variable, observing a significant association with age, diabetes, chronic obstructive pulmonary disease (COPD), and gait speed test. CONCLUSIONS: Our study revealed for the first time a significant correlation between physical and cognitive impairment in frail hypertensive elderly subjects.

Variability of Postural Stability and Plantar Pressure Parameters in Healthy Subjects Evaluated by a Novel Pressure Plate.

Background: Postural stability and plantar pressure parameters can be assessed by baropodometry; nevertheless, they are often affected by low repeatability. The aim of the study was to test the accuracy and repeatability of a novel resistive sensor pressure plate and to establish the most reliable baropodometric parameters. Methods: Accuracy and repeatability of the FM12050 BTS-Bioengineering plate measurements were assessed by using different weights in static conditions across three sessions. Subsequently, 20 healthy subjects were assessed by 30-s stabilometric analysis in bipedal standing with open eyes across four trials in two sessions, morning and afternoon. Results: Pressure plate repeatability in measuring the static weights was very high, and plate measurements were correlated to the scale measurements (Pearson's coefficient = 0.99). Percentage of load distribution between left and right foot and in rearfoot and forefoot regions showed the largest repeatability (coefficient of variation < 5%) across trials. Eventually, median and percentiles (25−75%) were reported for each parameter. Conclusions: This study helped to assess the accuracy and repeatability of a novel pressure plate in static conditions and to define the most reliable parameters for the assessment of postural stability and foot morphology. The present healthy-subject stabilometric dataset may be used as reference data in the evaluation of pathological populations.

Long-term effects of asymmetrical posture in boxing assessed by baropodometry.

BACKGROUND: Asymmetrical posture maintained over long training periods may affect phenotypic plasticity, resulting functional to sporting goal but negative to the locomotor system. Aim of this study was to quantitatively evaluate these long-term effects in competitive boxers. METHODS: Baropodometric analysis was used to assess 20 competitive boxers and 20 non-sportsmen in upright bipedal posture for 5 s and for 51.2 s with open (OE) and closed (CE) eyes. RESULTS: The boxers' group (BOX) showed a larger total foot load (TFL) (p=0.022) on the right foot and a larger rearfoot load (RfL) (P=0.011) on the left foot compared to non-sport controls (CTR). Moreover, a larger forefoot load (FfL) (P=0.001) on the right foot respect to left one was found in the BOX group, with the inversion of the RfL to FfL ratio (P=0.001) between two feet, while no significant differences were found in the CTR group. These findings, associated to a significantly larger center of foot angle (COF) in the BOX group, may indicate an anticlockwise rotation of the anatomical structures above the ankle joint of the right hemisoma respect to the left one, that appears to be consistent with the orthodox stance. Eventually, the BOX group showed a larger centre-of-pressure sway area (COPsa) in the OE condition than what measured in the CE and a significant difference in Romberg Index (BOX< CTR). CONCLUSIONS: The results of this study seem to confirm the theory of neuromuscular plasticity imprinted by the repetitive movements and long-lasting postures. Moreover, competitive boxers show an increase of proprioceptive function and a decrease of visual dependence on the postural control.

Role of physical exercise in an overlooked nutcracker syndrome occurred in a patient with diaphragmatic relaxation: a case report.

Background: Nutcracker syndrome (NCS) is caused by extrinsic compression of the left renal vein (LRV), usually between the abdominal aorta (AA) and superior mesenteric artery (SMA). This rare disease includes symptoms such as hematuria, left flank pain or abdominal pain, varicocele in males, proteinuria, anemia, gynecological symptoms (dyspareunia, dysmenorrhea). Case report: We report the case of a 48-year-old female patient, who experienced left abdominal colic after intensive physical exercise, finally resulting in a diagnosis of NCS. This abdominal pain was disabling for daily activities, it was controlled by analgesic drugs and led to hospital admissions. In-depth examinations were recommended to the patient to investigate the etiology of these attacks. A bad rotated and ectopic left kidney, which was located superior to the spleen, at the level of the left hemithorax base, was found due to the presence of a diaphragmatic relaxation in the posterior area, which caused an upward displacement of the kidney, part of the colon and omental fat. Because of the presence of a compression of the LRV by the SMA and the AA, the nephrologist diagnosed a NCS, presenting with abdominal pain following physical exercise, proteinuria and dysmenorrhea. Conservative treatment was chosen for the patient. Conclusions: The patient was recommended to engage in a moderate and regular physical activity, avoiding acute and intense exercise: hypopressive abdominal gymnastics was suggested. The role of physical exercise in triggering painful attacks and its role in rehabilitation to prevent the same attacks was crucial for the patient.

Indirect Structural Muscle Injuries of Lower Limb: Rehabilitation and Therapeutic Exercise.

Muscle injuries are the most common trauma in team and individual sports. The muscles most frequently affected are those of the lower limb, and in particular hamstrings, adductors, rectus femoris and calf muscles. Although several scientific studies have tried to propose different rehabilitation protocols, still too often the real rehabilitation process is not based on scientific knowledge, especially in non-elite athletes. Moreover, the growing use of physical and instrumental therapies has made it increasingly difficult to understand what can be truly effective. Therefore, the aim of the present paper is to review proposed therapeutic algorithms for muscle injuries, proposing a concise and practical summary. Following a three-phase rehabilitation protocol, this review aims to describe the conservative treatment of indirect structural muscle injuries, which are the more routinely found and more challenging type. For each phase, until return to training and return to sport are completed, the functional goal, the most appropriate practitioner, and the best possible treatment according to current evidence are expressed. Finally, the last section is focused on the specific exercise rehabilitation for the four main muscle groups with a structured explanatory timetable.