Successful Treatment of Kaposi Sarcoma-Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney-Liver Transplant: Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response.

After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma-associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory host responses typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of B cell neoplasias). These disorders are associated with a high mortality rate, often due to lack of prompt diagnosis, effective therapeutic approaches, and adequate follow-up. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe-for the first time-a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8-specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8-associated inflammatory disorders in posttransplant patients.

Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

PURPOSE: Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered. METHODS: Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. RESULTS: The easypod™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. CONCLUSIONS: The injection-recording system and other characteristics of easypod™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Ozone eliminates novel coronavirus Sars-CoV-2 in mucosal samples.

Recent investigations have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to resist on the surfaces and that the diffusion occurs through droplets that can remain suspended in the air as an aerosol. The ozone generated in situ from oxygen is an active ingredient with a 'biocidal' action, but little is known about its capacity to inactivate specifically SARS-CoV-2. Here we show, for the first time, the efficiency of the ozone treatment to neutralize the SARS-CoV-2 present in nasopharynx secretion samples with high viral load. Our data show that ozone is effective in SARS-CoV-2 elimination.

Hypertension: increase of collagen biosynthesis in arteries but not in veins.

In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation.

Processing cereal straws by steam explosion in a pilot plant to enhance digestibility in ruminants.

Wheat, barley and oat straws were treated by steam explosion (SE) and then washed with 50g/l NaOH solution. The SE treatment was optimized at batch scale on the basis of carbohydrate recovery. Stocks of fodder (300kg) were produced at 198 degrees C for 2.5min by a continuous reactor and used for in vivo digestibility tests carried out on sheep. The flow-sheet and the mass balances were obtained for the entire process. For the three straws, the water consumption has been 7.3kg/kg of straw. To delignify and improve the digestibility of the straws, 20g of NaOH/kg straw was used. The yield of fodder, lignin and hemicellulose is dependant on the nature of the starting straw. Delignified fodder (insoluble fraction) can be produced with a yield of 0.64, 0.59, 0.55, respectively, from wheat, barley and oat straw. SE improved the digestibility of the straw by 25%; alkaline washing further increased it by 9%. Balanced rations containing, on a DM basis, 1/4 of treated straw, had digestibility coefficients similar to those of commercial rations based on alfalfa.

Effect of critical dimension variation on SAW correlator energy.

The effect of critical dimension (CD) variation and metallization ratio on the efficiency of energy conversion of a surface acoustic wave (SAW) correlator is examined. We find that a 10% variation in the width of finger electrodes predicts only a 1% decrease in the efficiency of energy conversion. Furthermore, our model predicts that a metallization ratio of 0.74 represents an optimum value for energy extraction from the SAW by the interdigitated transducer (IDT).

The formation of hydroxyproline in collagen by cells grown in the absence of serum.

L-929 and 3T6 cells were conditioned to grow in a chemically defined medium lacking serum and ascorbate. Serum, when added, had a small stimulatory effect on the growth rate of the cells, but ascorbate had no effect either on the growth rate or on the rate of protein synthesis. These cells were also shown to lack gulonolactone oxidase activity and therefore could not synthesize their own ascorbate. Nevertheless, in the absence of serum and ascorbate both cell types were able to hydroxylate peptidyl proline to an appreciable extent. This suggests that reductants other than ascorbate can at least partially satisfy the requirement for a reductant in the prolyl hydroxylase reaction in vivo.

Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis.

Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.

Morphine and codeine are endogenous components of human cerebrospinal fluid.

We have examined cerebrospinal fluid (CSF) from twelve patients who were not on any medication and found them to contain both morphine and codeine in concentrations of 2 to 339 fmol/ml. These are comparable to the concentration of opioid peptides in spinal fluid. Both morphine and codeine are present mainly in conjugated form from which the free alkaloids can be released by acid hydrolysis.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Venous drainage of the stomach in the laboratory mouse (Mus musculus v. alba) and the laboratory rat (Rattus norvegicus v. alba).

The authors studied the venous drainage pattern of the stomach in 30 adult laboratory mice (Mus musculus v. alba) and in 31 adult laboratory rats (Rattus norvegicus v. alba) of both sexes. In mice, two basic patterns of the venous drainage of the stomach have been found, the first one (50.0% of cases) with a vena gastroepiploica dextra, while in the second pattern (50.0% of cases) the vena gastroepiploica dextra is absent and the venous blood from the curvatura major ventriculi and fundus ventriculi is drained only via the v. lienalis. In rats, three basic patterns of venous drainage of the stomach were found, the first group (35.2%) with the v. gastroepiploica dextra, the second group (38.4%) with prevalence of the v. gastrica sinistra and the third group with various tributaries of the v. lienalis from the stomach (25.6%). The vena gastrica sinistra is the only constant venous channel in both animals examined. Between interorganic venous anastomoses in the mouse and the rat no great differences exist. In spite of the great variability of veins the results indicate that it is possible to differentiate some basic patterns of the venous drainage of the stomach in the animals studied.

[Hormonal receptors in gingival inflammation]. / Studio dei recettori ormonali nell flogosi gengivali.

An empiric correlation between the inflamed gingiva and hormonal variations during physiological conditions such as pregnancy and menstrual cycle is already known. The demonstration of specific steroid receptors in human gingiva has suggested a relationship between the ovarian hormones and the dimensional changes of the gingiva. In this work, estrogen and progesterone receptors in healthy and inflamed gingiva have been studied.

[Circadian variability of IgE in children: effects of a thymic hormone (thymomodulin)]. / Variabilità circadiana delle IgE nel bambino: effetto di un ormone timico (timomodulina).

Since thymic factor activity can modulate immunoglobulin production, thymomodulin effect on IgE secretion was studied in thirty children (20 atopic and 10 control patients). Before treatment circadian variability of IgE was verified in all the children. Thymomodulin (3 mg/kg/die) was given daily for 30 days in both groups. Disappearance of circadian IgE variability were observed in atopic children, while no change of serum IgE circadian levels occurred in control group. On the basis of our results an improvement of IgE disregulation in atopic children may be postulated.

Nipple leiomyoma in man: a case report.

We describe a rare case of a man, 38 year old, with a nipple leiomyoma, and report the presentation as a small nodule of the areola spreading the nipple, the symptoms, the clinical signs, the treatment that includes a complete excision; free margins should be histologically established to prevent recurrence.

[Levels of Cathepsin D in breast cyst fluid]. / Dosaggio della Catepsina-D nel fluido di macrocisti della mammella.

Cathepsin-D was assayed in serum and in breast cyst fluid of 60 non neoplastic patients with GCD. The results are independent from cytological type or possible cyst relapse. Although the study confirms the high levels of Cat-D in breast cyst fluid no predictive value has been demonstrated. Its expression may be related to systemic endocrine factors.