Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of ...patients affected by RASopathies.
A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at "Scuola Medica Salernitana", Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls.
Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease.
Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.
Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in ...a consecutive unselected cohort of patients with RASopathies.
72 patients with a genetically confirmed RASopathy (Noonan syndrome NS, N=53; 29 LEOPARD syndrome LS, N=2; cardiofaciocutaneous syndrome CFCS, N=14; subjects showing co-occurring pathogenic variants in
and
, N=3) and an age- and sex-matched healthy controls were included in the study. Endocrine system involvement was investigated by assessing the thyroid function, pubertal development, auxological parameters, adrenal function and bone metabolism.
Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups.
The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.
In this study, we investigated the sorption–desorption behavior of imazamox (IMZ) and 2,4-DB (DB) in two typical acidic Mediterranean agricultural soils and the impact of these herbicides on ...culturable soil bacterial populations, enzyme activities and functional diversity when applied at concentrations higher than recommended doses (10×, 50×, 500×). Herbicide sorption was similar in both soils and IMZ was less retained compared to DB (~0.5 vs. 40 µg g−1 soil, respectively). IMZ desorption was remarkable (70–100%) while that of DB was more limited, i.e., ~40%. Three days after spiking (DAS), IMZ and DB significantly increased the number of soil-culturable heterotrophic bacteria, actinomycetes and Pseudomonas spp., soil respiration and the potential catabolic capacity of soil microbial communities. Soil dehydrogenase activity increased by ~56–70% in IMZ-treated soils while being reduced by ~33–41% in DB-treated ones. β-glucosidase activity showed a soil-dependent behavior, while the pattern of C source utilization suggested a change of soil microbial community structure after herbicide (especially DB) spiking. At 30 DAS, the herbicides’ impact on soil microorganisms, enzyme activity and functional diversity was still visible. Moreover, a toxic effect of DB (at 50× and 500×), but not IMZ, was recorded vs. Rhizobium sullae, the bacterial symbiont of Hedysarum coronarium. The obtained results indicated that IMZ and DB are poorly sorbed and highly desorbed by both soils. Moreover, at the tested concentrations, IMZ and DB can have short- and medium-term impacts on the microbial component and the related activity of the investigated soils, likely affecting a range of ecosystem services provided by soil microorganisms.
The fungicide fenhexamid N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide degraded rapidly by UV or sunlight irradiation, yielding ...7-chloro-6-hydroxy-2-(1-methylcyclohexyl)-1,3-benzoxazole (CHB) as a main photoproduct. CHB was isolated, and its effect on alcoholic fermentation of Saccharomyces cerevisiae was studied. The results indicate that the presence of CHB does not affect the extent of alcohol production. After 12 days, the amount of CHB in the fermentation medium decreased by ca. 65%. Only 25% of the missing CHB was recovered unchanged from yeasts, most likely because it was adsorbed on the yeast wall cell. The remaining part degraded during the fermentation process. Glucan and chitin, two potential adsorbents, which constitute yeast cell walls, exhibited affinity for CHB. Keywords: Fenhexamid; photodegradation; alcoholic fermentation; adsorption; Saccharomyces cerevisiae
Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved ...due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level.
Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome.
Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult.
Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM.
All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.
Fractures of the mandibular condylar process are common and account for up to 40% of all mandibular fractures. Penetration of the condylar head into the middle cranial fossa is, however, rare. We ...have found reports of only 43 cases since 1834. The diagnosis of intracranial condylar dislocation is difficult, there are usually no particular symptoms or neurological signs. As a result, detailed radiological studies are necessary. In the absence of clear radiographic images of the condylar structures, computed tomography (CT) is essential to locate the fragments and to investigate and monitor intracranial lesions. This paper describes the diagnostic and surgical procedures used in two cases of condylar dislocation and discusses them with reference to previous cases. The use of a titanium screw, which was positioned intracranially in the first case, has not, to our knowledge, been described previously.
The effect of undesalted dissolved organic matter (DOM) extracted from composts on the degradation, adsorption, and mobility of cyhalofop herbicide in soils was studied. A paddy-field sediment poor ...in organic matter (OM), an OM-rich forest soil, and DOM from agroindustrial or municipal waste compost were used. DOM increased the cyhalofop-acid but not the cyhalofop-butyl solubility in water. The degradation of cyhalofop-butyl in the sediment was slow, giving cyhalofop-acid as the only metabolite, whereas in forest soil, the process was faster, and three byproducts were detected. Soil pretreatment with DOM did not modify the degradation pattern but only reduced the adsorption of cyhalofop-butyl by soil, whereas it increased the adsorption of cyhalofop-acid. Among the cationic components of DOM solutions, the potassium ion seems to be related to the increased adsorption of the cyhalofop-acid in both OM-poor and OM-rich soils, yielding reversible complexes with the former and favoring hydrophobic interactions with the latter.
Azimsulfuron Sorption−Desorption on Soil Pusino, Alba; Pinna, M. Vittoria; Gessa, Carlo
Journal of agricultural and food chemistry,
06/2004, Letnik:
52, Številka:
11
Journal Article
Recenzirano
The sorption and desorption of the herbicide azimsulfuron, N-(4-dimethoxypyrimidin-2-yl)aminocarbonyl1-methyl-4-(2-methyl-2H-tetrazole-5-yl)1H-pyrazole-5-sulfonamide, were studied using five soils. ...Sorption isotherms conformed to the Freundlich equation. It was found that pH is the main factor influencing the sorption and that the sorption on soils was negatively correlated with pH. The highest level of sorption was measured on soils with low pH and high organic carbon content. Moreover, inorganic soil colloids, for example, smectite clay minerals and iron oxides, contributed to the sorption of azimsulfuron. Desorption was hysteretic on soils with high organic and inorganic colloid contents. Keywords: Azimsulfuron; herbicide; sorption; desorption; organic matter; humic acid
Following our pilot clinical study of combined IL-2/HSV-TK gene therapy for recurrent glioblastoma multiforme (GBM), we extended the protocol to a larger population of patients and evaluated safety, ...feasibility, and biological activity of treatment. A total of 12 patients received intratumor injection of retroviral vector-producing cells (RVPCs), followed by intravenous ganciclovir (GCV). Treatment was well tolerated with only minor adverse events. Transduction of tumor cells was demonstrated in tumor biopsies. A marked and persistent increase of intratumor and plasma Th1 cytokine levels was demonstrated after RVPC injection. At magnetic resonance imaging evaluation, two patients had a partial response (including a patient showing disappearance of a distant noninjected tumor mass), four had a minor response, four had stable disease, and two had progressive disease. The 6- and 12-month progression-free survival rates were 47 and 14%, respectively. The 6- and 12-month overall survival rates were 58 and 25%, respectively. In conclusion, the results of our clinical protocol of gene therapy for recurrent GBM, based on combined delivery of a suicide and a cytokine gene, demonstrate that intratumor injection of RVPCs was safe, provided effective transduction of the therapeutic genes to target tumor cells, and activated a systemic cytokine cascade, with tumor responses in 50% of cases.
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