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Magnetic reconnection is a process that converts magnetic energy into kinetic energy, both bulk and thermal. We study the energy partition in magnetotail reconnection in the presence of cold ion populations of ionospheric origin using kinetic simulations. We compare two simulations with one or two ion populations, but same ion moments. The ion distribution in the simulation with cold ions therefore corresponds to a non‐Maxwellian distribution with a large tail. The global energy budget does not change in the two cases, but when focusing on sub‐populations, the hot ion population (i.e., the tail of the velocity distribution function) gains more energy than the cold ion population (i.e., the core of the distribution). Hot and cold ions also gain different percentages of bulk and thermal energy. Plain Language Summary: Magnetic reconnection is a process that converts magnetic energy into acceleration (bulk kinetic energy) and heating (thermal kinetic energy). In the magnetosphere, we often see a cold plasma population of ionospheric origin, on top of the hot magnetospheric plasma. We study the energy partition in magnetotail reconnection in the presence of those cold ions using simulations. We compare two simulations with and without cold ions, but same global parameters. We observe that the total energy partition is not significantly different between the simulations. But when focusing on the cold ion simulation, we see that hot ions gains more energy than cold ions and also have a larger bulk over thermal energy gain. Key Points: The energy budget in magnetic reconnection is not significantly affected by cold ion beams for constant inflow plasma global parametersThe hotter ion population gains more energy during magnetic reconnection than the colder oneMost of the energy gain of hot ions is in the form of internal energy, while the energy transferred to the cold ions is more balanced [ABSTRACT FROM AUTHOR]

Objectives: To describe ultrasound‐guided microwave ablation as a minimally invasive treatment option for primary or metastatic hepatocellular carcinomas. Methods: Four client‐owned dogs underwent percutaneous ultrasound‐guided microwave ablation of three primary and one metastatic hepatocellular carcinoma, diagnosed on cytology/histopathology. In each case, multiple ultrasound‐guided thermal lesions were created in a 10 to 40 minutes ablation at 30 to 35 W. Real‐time monitoring was performed using 10 MHz diagnostic ultrasound transducers. The procedures were performed without complication and CT scans or abdominal ultrasounds were repeated immediately after. Patients were discharged on oral analgesia on the same day or 24 hours later. Results: Hepatocellular carcinomas were successfully ablated, which in some cases resulted in an improvement in clinical signs and laboratory values. The patients were followed up for a time ranging between 39 and 649 days and no evidence of disease progression was found. Three out of four patients are still alive at the time of writing. Clinical Significance: In these four patients, minimally invasive ultrasound‐guided microwave ablation was feasible and resulted in no immediate complications. Regular imaging follow‐up is recommended after the procedure and further studies on microwave ablation are warranted to establish its effectiveness in dogs with hepatocellular carcinomas. [ABSTRACT FROM AUTHOR]

Haemophilic arthropathy ( HA) is characterized by chronic proliferative synovitis leading to cartilage destruction and shares some pathological features with rheumatoid arthritis ( RA). Apoptosis has been implicated in RA pathogenesis, and an agonistic anti-Fas monoclonal antibody ( mAb) was found to induce RA fibroblast-like synoviocyte ( FLS) apoptosis and suppress synovial hyperplasia in animal models of RA. The aim of this study was to evaluate the effect of anti-Fas mAb on HA- FLS. FLS were isolated from knee synovial biopsies from six HA patients, six RA patients and six healthy subjects. The expression of Fas in synovial biopsies was investigated by immunohistochemistry. FLS were stimulated with anti-Fas mAb at different concentrations, alone or in combination with tumour necrosis factor-α ( TNF-α) and basic fibroblast growth factor ( bFGF). Fas expression in FLS was assessed by Western blot. Cell viability was studied with the WST-1 assay. Active caspase-3 levels were measured using ELISA and Western blot. A strong Fas-immunoreactivity was observed in different cells of HA synovium, including FLS, inflammatory cells and endothelial cells. Fas antigen was constitutively overexpressed in cultured HA- FLS. Anti-Fas mAb had a significant cytotoxicity on HA- FLS in a dose-dependent manner, either alone or in combination with TNF-α and bFGF. These cytotoxic effects were due to the ability of anti-Fas to induce HA- FLS apoptosis, as shown by the increased active caspase-3 levels. Anti-Fas mAb exhibited a more pronounced pro-apoptotic effect on HA- FLS than RA- FLS. Fas antigen is highly expressed on HA- FLS and its stimulation by anti-Fas mAb may be an effective strategy to induce HA- FLS apoptosis. [ABSTRACT FROM AUTHOR]

. Haemophilic arthropathy is the most common clinical manifestation of haemophilia, secondary to recurrent haemarthroses and chronic synovitis. Modern bleeding-preventing drugs have limited significantly the incidence of severe arthropathy, and primary approach is usually conservative. Use of intra-articular injections of hyaluronan acid is considered one of the most efficient treatments for early stages of articular degenerative diseases. Assessment of long-term effectiveness of intra-articular administration of hyaluronic acid (HA) in knees, ankles and elbows of patients affected by haemophilic arthropathy was done for 46 patients (10 elbows, 24 knees and 25 ankles) affected by haemophilic arthropathy. They received injections of HA and were evaluated with Visual Analogue Scale, Short Form-36, World Federation of Haemophilia score and Petterson score with a 6-year mean follow-up. Most of the patients showed improvement in pain relief and functional recovery without any complications: only a limited number of patients (8.6%) found poor results, undergoing surgery or other further treatments in the follow-up period for persistent pain or limitation. Viscosupplementation is an effective therapeutic strategy in early stages of haemophilic arthropathy, with no complications and long-term good clinical results. [ABSTRACT FROM AUTHOR]

Summary. Total knee arthroplasty (TKA) is a major orthopaedic surgery intervention, indicated for severe haemophilic arthropathy. The aim of our study was to analyse rehabilitation outcome in haemophilic patients after TKA. A consecutive series of 21 patients (23 knees) was retrospectively evaluated. The mean age was 37 ± 8 years (range 22-55). Physiotherapy treatment was performed twice a day for 5 days week−1, for 3 h day−1. Assessment included knee range of motion (ROM), Visual Analogue Scale (VAS) for pain evaluation, Western Ontario and McMaster University (WOMAC) Score for functional outcome, Medical Research Council Scale (MRC) for quadriceps muscle strength evaluation, incidence of adverse events and a self-reported questionnaire. The patients'data were recorded before surgery (t0), at Rehabilitation Unit admission (t1), before discharge (t2) and at follow-up (t3), 11-48 months after rehabilitation. Western Ontario and McMaster University Score (ref. score: 0-96) was 56.7 ± 12 at t0 and 6.2 ± 6 at t3 (t3 vs. t0: P < 0.001). Visual Analogue Scale (ref. score: 0-10) decreased from 5.0 ± 2 at t1 to 2.1 ± 2 at t2 (t2 vs. t1: P < 0.05) and to 0.1 ± 0 at t3 (t3 vs. t2: P < 0.05). Flexion degrees increased from 43.4 ± 21° at t1 to 80.2 ± 15° at t2 (t2 vs. t1: P < 0.001) and to 95.0 ± 15° at t3 (t3 vs t2: P < 0.05). According to MRC (ref. score: 0-5), quadriceps muscle strength increased from 2.3 ± 0.6 at t1 to 3.6 ± 0.5 at t2 (t2 vs. t1: P < 0.05). Adverse events were found in four patients. Patients' satisfaction on their outcome at follow-up was referred as good by 72% of patients or excellent by 28% of patients. Postsurgical intensive rehabilitation in haemophilic patients resulted effective, safe and feasible. [ABSTRACT FROM AUTHOR]

Haemarthrosis triggers haemophilic arthropathy (HA) because bleeding starts synovitis immediately, damages cartilage and leads to loss of function and disability. The aim of our study was to investigate the capacity of ultrasonography (US) in detecting bleeding and joint damage in HA. The joints of 62 patients (pts) with haemophilia A or haemophilia B were consecutively evaluated and scored (score ranging from 0 to 21) for effusion (E), bone remodelling (BR), cartilage damage (CD), synovial hypertrophy (SH), haemosiderin (H), osteophytes (O), haemarthrosis (Hae), erosion (Er) and fibrotic septa (FS) with US. X-rays [Pettersson Score (PXS)] were performed in 61 patients and clinical evaluation [World Federation Haemophiliac orthopaedic score (WFHO)] was performed in all patients. A total of 20 healthy subjects and 20 patients affected by Rheumatoid Arthritis (RA) were used as controls. Power Doppler US (PDUS) was performed in all patients on the knee, ankle and elbow joints. A total of 83 joints were studied (50 knees; 12 elbows and 21 ankles). US showed effusion in 57 joint, bone remodelling in 62, cartilage damage in 64, synovial hypertrophy in 45, haemosiderin in 39, osteophytes in 30, haemarthrosis in 24, erosion in 5 and fibrotic septa in 3. The X-rays score showed remodelling in 47 joints, narrowing joint space in 44, displacement/angulation in 39, osteoporosis in 42, subchondral irregularity in 44, subchondral cyst formation in 37, osteophytes in 36 and erosions in 25. The US score in healthy subjects was always ≤5 (range 0 to 4). In haemophiliacs, 34 of 83 joints showed US score ≤5, and 49 US score >5. Joints with US score ≤5 had a low PXS (SRCC = 0.375, P < 0.01) and joints with US score >5 showed a high PXS (SRCC = 0.440, P < 0.01). A significant correlation between US score and PXS for bone remodelling [Spearman's rho Correlation Coefficient (SRCC) = 0.429, P < 0.01] and for osteophytes (SRCC = 0.308 P < 0.05) was found. The correlation between the US score and number of bleedings in 83 joints was very significant (SRCC = 0.375, P < 0.01). A total of 24 bleeding joints were identified and verified with aspiration of haematic fluid. US may detect bone and cartilage alterations and synovitis. Indeed, PDUS identified bleeding also in asymptomatic joints and was able to show different entity of haemarthrosis. US may be a feasible and reliable tool to evaluate joint modifications in HA. [ABSTRACT FROM AUTHOR]

Aim MAS064D (Sebclair®) is a novel steroid-free cream containing multiple active ingredients. Objective of this pilot study was to evaluate the efficacy and safety of MAS064D in the treatment of mild to moderate SD of the face. Methods Patients ( n = 60) with SD were randomized to receive MAS064D ( n = 40) or a matching vehicle ( n = 20). The primary study endpoint was investigators’ global assessment (IGA) score at day 28, compared with baseline. Secondary endpoints included: IGA score at day 14; investigators’ assessment of erythema and scaling; patients’ assessment of burning/stinging, pruritus and global response to MAS064D; resort to rescue medication; quality of life. Results Use of MAS064D for 4 weeks was associated with a higher percentage of success in the MAS064D group than in the vehicle group (~68% vs 11%, P < 0.0001). The effects of MAS064D were significantly better than those of vehicle for investigator-assessed erythema and scaling, and patients’ assessed pruritus and global response to MAS064D ( P  0.01). No patient in the MAS064D group required rescue medication, compared with two patients in the vehicle group. Four patients (two each in the MAS064D and vehicle groups) reported a total of six non-serious adverse events. Conclusions MAS064D appears to be an effective and well tolerated cream for the treatment of mild to moderate SD of the face. Further clinical evaluation of MAS064D in SD is warranted. [ABSTRACT FROM AUTHOR]

The apical seal of roots obturated with a dentin bonding agent and Thermafill with and without the use of sodium hypochlorite as an irrigating solution was compared by a dye leakage test. Roots obturated with Thermafill and a zinc oxide eugenol sealer were used as controls. Thirty-eight roots were prepared chemomechanically and divided into three experimental groups. The teeth of group 1 were filled with Thermafill and the dentin bonding agent using sodium hypochlorite as the irrigant. The teeth of group 2 were filled in the same way, but saline solution was used as the irrigant. Before the root canal was filled the smear layer was removed from the root canal walls of both groups by rinsing the root canal with a 17% EDTA solution. The teeth of group 3 were filled with Thermafill and zinc oxide eugenol sealer. The teeth were immersed in 2% methylene blue solution. The root fillings of groups 1 and 2 leaked significantly more than those of group 3. The resin-dentin-gutta-percha interface of group 1 was observed by scanning electron microscopy and showed a typical hybrid layer. An intimate contact between resin and dentin was present in group 2, but a resin-dentin inter-diffusion zone was only occasionally observed. The use of dental adhesives and the hybrid layer formation did not improve the seal of Thermafill root canal fillings. [ABSTRACT FROM AUTHOR]

The internal organization of plasma membranes was studied in seven subjects with pemphigus vulgaris and in one subject with familial pemphigus using the freeze-fracture technique. The results obtained seem to suggest that the acantholytic process is produced in a similar fashion whatever the pathogenic agent and that desmosomes represent the "target" membrane specializations in the acantholytic phenomena. The reduction and eventual disappearance of desmosomal particle aggregations is seemingly accompanied by an increase in gap junctions. [ABSTRACT FROM AUTHOR]

The following findings were striking in two young patients, suffering from mycosis fungoides: I) paracryslalline bodies, probably of a proteic nature, both in the cytoplasm of well-preserved mycosis fungoides cells and in cells undergoing degeneration; 2) a remarkable number of mast cells mixed with mycosis fungoides cells and mast cell granules in the intercellular spaces of the epidermis, close to Pautrier's abscesses. [ABSTRACT FROM AUTHOR]

From their ultrastructural study of incontinenti pigmenti, the authors confirm that in this condition there is no pigmentary anomaly, but that pigmentation is the last step of a still unknown process. At birth those who are affected display an intracellular edema which leads to the formation of a vesicobullla. In all 3 stages, the epidermis shows dyskeratotoc cells and a transient pigmentary discharge. [ABSTRACT FROM AUTHOR]

A letter to the editor regarding a risk sharing model for managing treatment with factor VIIa in hemophilia patients with inhibitors is presented.

A letter to the editor is presented which discusses the case of a young haemophilic patient who undergone a successful surgical treatment of quadratus femoris muscle's complete symptomatic ossification.

This article presents a medical investigation report of a case of contact dermatitis to coal tar in psoriasis. A biopsy test of the eczematous psoriatic areas on the hands of a woman, suffering from arthropatic psoriasis, showed the histology of psoriasis plus spongiosis which confirmed the hypersensitivity to the tar. It is examined that hypersensitivity to tar can develop through a light-mediated mechanism but is rare in existence.

Cancer-associated fibroblasts (CAFs) are key regulators of tumorigenesis and promising targets for next-generation therapies. We discovered that cancer cell-derived activin A reprograms fibroblasts into pro-tumorigenic CAFs. Mechanistically, this occurs via Smad2-mediated transcriptional regulation of the formin mDia2, which directly promotes filopodia formation and cell migration. mDia2 also induces expression of CAF marker genes through prevention of p53 nuclear accumulation, resulting in the production of a pro-tumorigenic matrisome and secretome. The translational relevance of this finding is reflected by activin A overexpression in tumor cells and of mDia2 in the stroma of skin cancer and other malignancies and the correlation of high activin A/mDia2 levels with poor patient survival. Blockade of this signaling axis using inhibitors of activin, activin receptors, or mDia2 suppressed cancer cell malignancy and squamous carcinogenesis in 3D organotypic cultures, ex vivo, and in vivo, providing a rationale for pharmacological inhibition of activin A-mDia2 signaling in stratified cancer patients., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

We investigated the efficacy of rosmarinic acid (RA) in preventing lipid peroxidation and increased activity of acetylcholinesterase (AChE) in the brain of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures (striatum, cortex and hippocampus) were removed for experimental assays. The results demonstrated that the treatment with RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum (47%) of diabetic rats when compared with the control. In addition, it was found that hyperglycaemia caused significant increased in the activity of AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks. In conclusion, the present findings showed that treatment with RA prevents the lipid peroxidation and consequently the increase in AChE activity in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and prevent damage oxidative in brain in the diabetic state. Thus, we can suggest that RA could be a promising compound in the complementary therapy in diabetes., (Copyright © 2013 John Wiley & Sons, Ltd.)

A previously developed mathematical model is used to investigate the role of some hemodynamic, regulatory, and osmotic factors in the development of symptomatic hypotension during hemodialysis. Sensitivity analysis of the model parameters suggests that a decrease in atrial pressure, with a consequent fall in cardiac output (Frank-Starling mechanism), is the primary hemodynamic perturbation induced by ultrafiltration. Also, during the first hours of a hemodialysis session, the sympathetic mechanism working on systemic resistance is the main factor responsible for arterial pressure maintenance, and the physiological response is probably characterized by a prevalence of the cardiopulmonary over the arterial baroreflex control. During this period, a decrease in plasma osmolarity, caused mainly by urea removal, may contribute to the reduction of vascular refilling. During the last hours of the session, the arterial pressure level is also significantly affected by other factors that influence vascular refilling and mean circulatory filling pressure (systemic compliance; action of feedback mechanisms working on venous unstressed volume; plasma oncotic pressure; and, especially, capillary wall permeability and interstitial space elastance). Simulation of hemodialysis with different modalities emphasizes the importance of avoiding high ultrafiltration rates and of maintaining the sodium concentration in the dialysate close to the sodium concentration of the extracellular fluid to limit the risk of symptomatic hypotension. Higher values of sodium in the dialysate are, however, associated with poor sodium removal from the extracellular pool with risks of interdialytic morbidity. In the future, the model may be used to optimize the ultrafiltration rate and sodium profile in the dialysate according to individual patient prescriptions.

A mathematical model of the hemodynamic response to hemodialysis is presented. This model includes the dynamics of sodium, urea, and potassium in the intracellular and extracellular pools; fluid balance equations for the intracellular, interstitial, and plasma volumes; systemic and pulmonary hemodynamics; and the action of several short-term arterial pressure control mechanisms. The control mechanisms are triggered by information coming from both arterial and cardiopulmonary pressoreceptors, and they work on systemic arterial resistance, heart rate, and systemic venous unstressed volume. Moreover, the model hypothesizes that decreasing left atrial pressure below a given threshold causes a paradoxical withdrawal of the sympathetic drive and a consequent vasodepressor syncope. The model is used to simulate the pattern of the main hemodynamic quantities (systemic arterial pressure, heart rate, total systemic resistance, and cardiac output) during hemodialysis in several groups of patients (both hypotension resistant and hypotension prone) whose data were drawn from the clinical literature. The simulation results point out that the model is able to reproduce a variety of different conditions, including no hypotension, moderate hypotension, and severe hypotension with ultimate vasodepressor syncope, by adjusting a few parameters with clear physiological meanings. Hypotension is principally imputed to a loss of the sympathetic mechanisms working on systemic resistance and to an impairment of vascular refilling at the capillary wall. The results suggest that hypotension during hemodialysis is a complex phenomenon that depends on the superimposition of several concomitant factors working together that can lead to a variety of distinct individual patterns.

The rising problem of biocompatibility is encouraging the development of new dialysis membranes, but the high cost of synthetic ones precludes their wide use. The authors compared the biocompatibility of cuprophan (CU), cellulose acetate (CA), and hemophan (HE), evaluating both in vitro and in vivo polymorphonuclear leukocyte (PMN) oxidative metabolism activation by resting chemiluminescence and complement activation by C3a; in vivo PMN counts during dialysis were also performed. The lowest increase in in vitro PMN resting chemiluminescence using HE was + 71.3% with CA, +49.3% with CU, and + 21.4% with HE (p less than 0.001 versus CA and CU); furthermore, HE did not significantly stimulate PMN resting chemiluminescence during in vivo hemodialysis: + 56.6% with CA, + 38.8% with CU, and + 3.7% with HE (p less than 0.01 versus CU and p less than 0.001 versus CA). C3a concentration increased with all membranes both in vitro and in vivo, but HE (in both experimental conditions) showed the lowest increase at any time (p less than 0.001 versus CA and CU). After 15 min of dialysis, PMN count dropped to 20.3% of basal values with CU, to 49.8% with CA, and to 76.5% with HE (p less than 0.001 versus CU and CA). Among cellulosic membranes, HE is the most biocompatible and appears to be an important step in preventing blood-membrane interactions and related complications.