Insight into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor.

Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called 'soft' signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor.

BACKGROUND: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. OBJECTIVES: Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. METHODS: We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. RESULTS: In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. CONCLUSIONS: Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms.

Facial emotion expressivity in patients with Parkinson's and Alzheimer's disease.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters' responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters' response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.

Relationship between the interlimb transfer of a visuomotor learning task and interhemispheric inhibition in healthy humans.

The "interlimb transfer" phenomenon consists of improved performance of the trained and untrained contralateral limbs after unilateral motor practice. We here assessed whether a visuomotor learning task can be transferred from one hemisphere to the other, whether this occurs symmetrically, and the cortical neurophysiological correlates of this phenomenon, focusing on interhemispheric connectivity measures. We enrolled 33 healthy subjects (age range: 24-73 years). Participants underwent two randomized sessions, which investigated the transfer from the dominant to the nondominant hand and vice versa. Measures of cortical and intracortical excitability and interhemispheric inhibition were assessed through transcranial magnetic stimulation before and after a visuomotor task. The execution of the visuomotor task led to an improvement in motor performance with the dominant and nondominant hands and induced a decrease in intracortical inhibition in the trained hemisphere. Participants were also able to transfer the visuomotor learned skill. The interlimb transfer, however, only occurred from the dominant to the nondominant hand and positively correlated with individual learning-related changes in interhemispheric inhibition. We here demonstrated that the "interlimb transfer" of a visuomotor task occurs asymmetrically and relates to the modulation of specific inhibitory interhemispheric connections. The study results have pathophysiological, clinical, and neuro-rehabilitative implications.

Objective assessment of the effects of opicapone in Parkinson's disease through kinematic analysis.

BACKGROUND: Opicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients. OBJECTIVES: In this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements. METHODS: We enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3). RESULTS: Movement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session. CONCLUSIONS: This study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

Vascular Biology of Arterial Aneurysms.

BACKGROUND: This review aims to analyze biomolecular and cellular events responsible for arterial aneurysm formation with particular attention to vascular remodeling that determines the initiation and the progression of arterial aneurysm, till rupture. METHODS: This review was conducted searching libraries such as Web of Science, Scopus, ScienceDirect, and MEDLINE. Used keywords with various combinations were "arterial aneurysms," "biology," "genetics," "proteomics," "molecular," "pathophysiology," and extracellular matrix". RESULTS: There are several genetic alterations responsible of syndromic and nonsyndromic disease that predispose to aneurysm formation. Extracellular matrix imbalance, mainly due to the alteration of vascular smooth muscle cells homeostasis, overexpression of metalloproteinases, and cytokines activation, determines weakness of the arterial wall that dilates thus causing aneurysmal disease. Altered mechanotransduction in the extracellular matrix may also trigger and sustain anomalous cellular and biochemical signaling. Different cell population such as vascular smooth muscle cells, macrophages, perivascular adipose tissue cells, and vascular wall resident stem cells are all involved at different levels. CONCLUSIONS: Improving knowledge in vascular biology may help researchers and physicians in better targeting aneurysmal disease to better prevent and better treat such important disease.

Molecular Determinants of Chronic Venous Disease: A Comprehensive Review.

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD.

Childhood Obesity: Insight into Kidney Involvement.

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.

Risk Factors for Bleeding Varicose Veins in Patients with Chronic Venous Disease.

Background and Objectives: Chronic venous disease (CVD) is a widespread clinical condition that is very common in western countries in the adult general population with a wide range of clinical manifestations, such as varicose veins (VVs) that in certain circumstances may complicate with rupture and subsequent bleeding that may even be fatal. The aim of this study is to evaluate risk factors for bleeding VVs. Materials and Methods: This is a retrospective study conducted in patients with CVD complicating with bleeding of VVs over a 4-year period (2019-2022). A random sample, for the same 4-year period and with a 3:1 ratio, was selected from other CVD patients without VVs bleeding that served as the control group. Results: From a global population of 1048 patients with CVD over a 4-year period, a total of 33 patients (3.15%) with VVs bleeding were selected. A group of 99 patients without VVs bleeding were randomly selected from the total population of 1048 patients with CVD. Findings of this study showed that advanced clinical stage of CVD (i.e., C4b stage), advanced age, living alone, suffering from cardiovascular co-morbidity (i.e., hypertension and CHF), assuming certain drugs that act on blood coagulation (i.e., aspirin, anticoagulants), assuming psychotropic medication, having particular venous reflux patterns (i.e., below-knee GSV reflux, non-saphenous veins reflux, Cockett's perforators reflux), and not having been assessed and treated previously for CVD (i.e., with VADs, CT, or surgery) may predispose a high risk for bleeding VVs. Conclusions: Bleeding VVs may be a life-threatening complications of CVD patients, and monitoring risk factors found in this study and others that, hopefully, may be discovered in the future through further focused research will help to reduce the impact of this problem in this patient population.

Transcatheter Arterial Embolization (TAE) of Cancer-Related Bleeding.

Background and Objectives: Roughly 10% of cancer patients experience an episode of bleeding. The bleeding severity can range from occasional trivial bleeds to major bleeding. The treatment for the bleeding may vary, depending on the clinical condition and anatomical site, and may include various strategies, among which TAE is a cornerstone of major bleeding management. However, the existing literature on tumor hemorrhages is inconsistent. The objective of this multicenter retrospective cohort study was to evaluate the effectiveness and safety of arterial embolization in the treatment of tumor hemorrhages in patients with solid cancers. Materials and Methods: The data for patients with solid cancers undergoing TAE for the management of tumor hemorrhages from January 2020 to May 2023 were gathered. Results: A total of 92 patients with cancer-related bleeding were treated between January 2020 and May 2023. No bleeding was detected by X-ray angiography (XA) in 12 (13%) cases; therefore, a blind embolization was performed. The most common bleeding site was the liver (21.7%). A total of 66 tumor hemorrhages were spontaneous. The most commonly used embolic agent was polyvinyl alcohol (PVA) particles (30.4%). Technical success was achieved in 82 (89.1%) cases, with an 84.8% clinical success rate related to 14 cases of rebleeding. Proximal embolization was performed for 19 (20.7%) patients. Complications were recorded for 10 (10.9%) patients. The 30-day bleeding-related mortality was 15.2%. The technical success, clinical success, proximal embolization rate, and 30-day rebleeding were worse in the subset of patients undergoing TAE with coils. Conclusions: Transcatheter arterial embolization (TAE) represents a viable and potentially life-saving therapeutic approach in the management of tumor hemorrhages, demonstrating a notable effectiveness and safety. The TAE of bleeding tumors using coils resulted in a higher rate of non-superselective proximal embolization, with a trend toward lower clinical success rates and higher rebleeding episodes.

A Multicenter Retrospective Cohort Study Evaluating the Clinical Outcomes of Patients with Coagulopathy Undergoing Transcatheter Arterial Embolization (TAE) for Acute Non-Neurovascular Bleeding.

Background and Objectives: Transcatheter arterial embolization (TAE) is the mainstay of treatment for acute major hemorrhage, even in patients with coagulopathy and spontaneous bleeding. Coagulopathy is associated with worsening bleeding severity and higher mortality and clinical failure rates. Furthermore, some unanswered questions remain, such as the definition of coagulopathy, the indication for TAE or conservative treatment, and the choice of embolic agent. This study aims to assess the efficacy and safety of TAE for spontaneous non-neurovascular acute bleeding in patients with coagulopathy. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients with coagulopathy who had undergone, from January 2018 to May 2023, transcatheter arterial embolization for the management of spontaneous hemorrhages. Results: During the study interval (January 2018-May 2023), 120 patients with coagulopathy underwent TAE for spontaneous non-neurovascular acute bleeding. The abdominal wall was the most common bleeding site (72.5%). The most commonly used embolic agent was polyvinyl alcohol (PVA) particles or microspheres (25.0%), whereas coils and gelatin sponge together accounted for 32.5% of the embolic agents used. Technical success was achieved in all cases, with a 92.5% clinical success rate related to 9 cases of rebleeding. Complications were recorded in 12 (10%) patients. Clinical success was significantly better in the group of patients who underwent correction of the coagulopathy within 24 h of TAE. Conclusions: Transcatheter arterial embolization (TAE) is effective and safe for the management of acute non-neurovascular bleeding in patients with coagulopathy. Correction of coagulopathy should not delay TAE and vice versa, as better clinical outcomes were noted in the subgroup of patients undergoing correction of coagulopathy within 24 h of TAE.

Endovascular Treatment of Visceral Artery Pseudoaneurysms with Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs).

Background and Objectives: Treatment of visceral artery pseudoaneurysms (VAPs) is always indicated regardless of their diameters, as their risk of rupture is significantly higher than that of visceral artery aneurysms. The invasiveness of surgery and its associated complications have led to a shift in favor of radiological interventions as the initial treatment of choice. However, there are still some unanswered questions on endovascular treatment of VAPs regarding the optimal endovascular technique and the efficacy and safety outcomes. The purpose of this multicenter study was to retrospectively evaluate the effectiveness and safety of endovascular treatment of visceral pseudoaneurysms using Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs). Materials and Methods: Consecutive patients who underwent endovascular embolization with EVOH-based NALEAs for visceral artery pseudoaneurysms between January 2018 and June 2023 were retrospectively evaluated. Results: 38 embolizations were performed. Technical success was achieved in all patients. The clinical success rate was high (92.1% overall), with no significant differences between ruptured and unruptured VAPs (p = 0.679). Seven patients (18.4%) experienced procedure-related complications, related to one case of non-target embolization, four splenic abscesses due to end-organ infarction, and two femoral pseudoaneurysms. The rates of procedure-related complications, end-organ infarction, and vascular access-site complications did not significantly differ between ruptured and unruptured VAPs (p > 0.05). Conclusions: Both ruptured and unruptured visceral pseudoaneurysms can be effectively and safely treated with NALEA-based endovascular embolization. We suggest considering the use of NALEAs, particularly in specific clinical cases that highlight their advantages, including patients with coagulopathy, fragile vessels, and embolization targets that are located at a considerable distance from the microcatheter tip and are otherwise difficult to reach.

Vaporization and thermodynamics of the Cs2 O-MoO3 system studied using high-temperature mass spectrometry.

RATIONALE: Cesium and molybdenum are fission products of uranium dioxide fuel in nuclear reactors, which interact with each other depending on the oxygen potential of the fuel. This leads to formation of various compounds of the Cs2 O-MoO3 system, which are exposed to high temperatures during operation of a reactor or a severe accident at a nuclear power plant. This is why the study of the vaporization and thermodynamics of compounds in the Cs2 O-MoO3 system is important. METHODS: Synthesis of the compounds in the Cs2 O-MoO3 system was carried out by sintering Cs2 MoO4 and MoO3 . Characterization of the samples was accomplished with the use of XRD, TGA/DSC/DTA, IR spectroscopy, and ICP emission spectroscopy. Vaporization of the samples under study was carried out from a platinum effusion cell using an MS-1301 mass spectrometer developed for high-temperature studies of low-volatility substances. RESULTS: The temperature dependences of partial pressures of vapor species were determined over pure MoO3 and Cs2 MoO4 in the ranges 870-1000 K and 1030-1198 K, respectively. MoO3 , Mo2 O6 , Mo3 O9 , Mo4 O12 , and Mo5 O15 were shown to be the main vapor species over the Cs2 O-MoO3 system in the temperature range 850-1020 K. The component activities, Gibbs energies of mixing, and excess Gibbs energies were obtained as functions of the component concentration at 900, 950, and 1000 K. CONCLUSIONS: The thermodynamic properties of the Cs2 O-MoO3 system found in the study evidenced negative deviations from ideality. The MoO3 and Cs2 MoO4 partial molar enthalpies of mixing, the Cs2 MoO4 partial vaporization enthalpy, and the total enthalpy of mixing in the Cs2 O-MoO3 system at 1000 K were obtained for the first time.

High-temperature mass spectrometric study of vaporization and thermodynamics of the Cs2 O-B2 O3 system: Review and experimental investigation.

RATIONALE: The compounds in the Cs2 O-B2 O3 system are of particular interest for nuclear applications since cesium borates may be formed during accidents in nuclear reactors, affecting the rate of release of radiotoxic isotopes into the environment. Thus, information on the vaporization and thermodynamic properties of cesium borates is necessary for simulation and modeling of the isotope release processes taking place during the nuclear reactor accidents. METHODS: Compounds in the Cs2 O-B2 O3 system were synthesized by the co-crystallization method with subsequent sintering. The sample characterization was carried out using XRD, TGA/DSC/DTA, IR spectroscopy, and ICP atomic emission spectroscopy. The vaporization and thermodynamics of the samples under consideration were investigated using an MS-1301 mass spectrometer and a single molybdenum effusion cell. The electron ionization method was employed for ionization of the vapor species with an electron energy of 30 eV. The scale of the ionizing voltage was calibrated according to the traditional technique by measuring the appearance energy of gold in the mass spectrum of the vapor over pure gold. RESULTS: The main vapor species over the samples in the Cs2 O-B2 O3 system were CsBO2 and Cs2 B2 O4 in the temperature range 789-1215 K and in the concentration range 0.1-0.5 mole fraction of Cs2 O. The temperature dependences of the CsBO2 and Cs2 B2 O4 partial pressures over cesium borate were obtained in the temperature range 767-990 K. The CsBO2 and B2 O3 activities, the Gibbs energies of mixing, the excess Gibbs energies, the partial mole enthalpies of mixing, and total enthalpies of mixing were determined as functions of temperature and composition of the condensed phase. CONCLUSIONS: As the Cs2 O and B2 O3 activity values evidenced, negative deviations from the ideal behavior were observed in the Cs2 O-B2 O3 system in the temperature range 800-1000 K. The total enthalpies of mixing and the Gibbs energies of mixing in the Cs2 O-B2 O3 system were compared with the literature data, illustrating their mutual agreement.

High-temperature mass spectrometric study of thermodynamic properties in the UO2 -ZrO2 system.

RATIONALE: The UO2 -ZrO2 solid solution at high temperatures is the key system of modern nuclear science and technology in the context of the safety operation of nuclear cycles, the consequences of severe accidents, and the incorporation of nuclear waste. Urgent needs of the continuation of experimental studies of this system at temperatures up to 3000 K are aimed at preventing severe accidents similar to Chernobyl and Fukushima when the thermodynamic approach is used for the prediction of high-temperature behavior of materials. METHODS: This investigation was carried out using the Knudsen effusion mass spectrometric method using the MS-1301 magnetic sector mass spectrometer. The samples in the UO2 -ZrO2 system were vaporized from a tungsten effusion cell. Vapor species effusing from the cell were ionized at an electron ionization energy of 70 eV. RESULTS: The vaporization and thermodynamics of pure UO2 and ZrO2 as well as of the samples in the UO2 -ZrO2 system were studied in the range 2000-2730 K. The temperature dependences of the partial vapor pressures of UO and UO2 over pure UO2 were obtained at 2060-2456 K, which agreed with the literature results. The partial vapor pressures of UO, UO2 , ZrO, and ZrO2 , the vaporization rates, and the UO2 and ZrO2 activities in the UO2 -ZrO2 solid solutions were determined at 2370, 2490, 2570, and 2730 K. CONCLUSIONS: The component activities and excess Gibbs energies of the UO2 -ZrO2 system indicated a change in deviations from the ideal behavior from positive to negative with the temperature increase from 2370 to 2730 K. The thermodynamic functions of formation from the oxides of the solid solutions in the UO2 -ZrO2 system such as Gibbs energies as well as the enthalpies and entropies of formation were obtained for the first time at 2550 K in the composition range 0.89-1.00 ZrO2 mole fraction.

Clinical Audit of Minimally Invasive Nonsurgical Techniques in Active Periodontal Therapy.

AIMS: Periodontitis is one of the most widespread diseases worldwide. Many efforts have been made to increase the efficacy of periodontitis therapy as much as possible. Recently, minimally invasive nonsurgical techniques (MINST) were introduced in the periodontal field as an alternative to minimally invasive surgical techniques (MIST). This clinical audit aims to evaluate the results of MINST in the initial phase of treatment for periodontitis. MATERIALS AND METHODS: One hundred seven patients with periodontitis who were treated with MINST between 2013 and 2017 and reevaluated after 2 months were included in this clinical audit. The primary outcome analyzed was the proportion of pocket closure. The secondary outcomes were tooth extraction before active periodontal therapy, full-mouth plaque score (FMPS) change, full-mouth bleeding score (FMBS) change, average probing pocket depth (PPD) reduction, and average clinical attachment level (CAL) gain between the baseline and reevaluation values. RESULTS: A total of 2,407 teeth were included in the analysis. At the patient level, the treatment resulted in a mean pocket closure rate of 71.6 ± 15.7% for sites with an initial PPD ≥5 mm. The treatment was statistically significantly (p < 0.001) more effective with respect to the primary outcome compared with expected values reported in a recent meta-analysis (57%). The subgroup analysis revealed statistically significant differences between single and multirooted teeth and between shallow (5-6 mm) and deep pockets (≥7 mm) at the baseline. CONCLUSION: Nonsurgical periodontal therapy with MINST achieved satisfactory results that were better than expected based on the scientific literature. Single-rooted and shallow pockets showed the best proportion of pocket closure at the reevaluation after treatment. CLINICAL SIGNIFICANCE: Minimally invasive nonsurgical techniques can be the treatment of choice when approaching periodontally diseased patients with nonsurgical periodontal therapy.

Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP).

The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5-T12 injury, and grade A or B of the ASIA Impairment Scale (AIS), admitted within 8 h, hemodynamically stable, were randomized to MP according to the NASCIS III protocol or EPO iv (500 UI/kg, repeated at 24 and 48 h). Patients were assessed by an investigator blind to treatment assignment at baseline and at day 3, 7, 14, 30, 60 and 90. Primary end point: number of responders (reduction of at least one AIS grade). Secondary end points: treatment safety and the effects of drugs on a number of disability measures. Frequentistic and post hoc Bayesian analyses were performed. Eight patients were randomized to MP and 11 to EPO. Three patients (27.3 %) on EPO and no patients on MP reached the primary end point (p = 0.17). No significant differences were found for the other disability measures. No adverse events or serious adverse events were reported in both groups. The Bayesian analysis detected a 91.8 % chance of achieving higher success rates on the primary end point with EPO in the intention-to-treat population with a 95 % chance the difference between EPO and MP falling in the range (-0.10, 0.51) and a median value of 0.2. The results of Bayesian analysis favored the experimental treatment.

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease.

Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.