Efficacy of bio- and neurofeedback for depression: a meta-analysis.

BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis an effect size of Hedges' g = 1.050. Moderator analyses indicate that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

Gulliver's virtual travels: active embodiment in extreme body sizes for modulating our body representations.

It is noted that the perceptual experience of body and space can be modulated by changing the action capabilities or by manipulating the perceived body dimensions through a multisensory stimulation. This study adds to pre-existing literature by investigating the alterations in bodily experience following embodiment to both enlarged and shrunked bodies, while participants actively navigated in a virtual environment. A normal-sized body served as a reference condition. After each embodied navigation, participants estimated the height and width of three different body parts. Results revealed that the embodiment over shrunked body induced a significant reduction in participants' body image, while no changes were reported after the embodiment over the enlarged body. Findings were discussed in terms of previous literature exploring the constraints implicated in the ownership over different bodies.

Rehabilitations with immediate loading of one-piece implants stabilized with intraoral welding.

The authors present an implant prosthesis procedure that uses screws on one-piece implants connected with a titanium pin at their abutment level and one supporter titanium bar in order to guarantee immediate stabilization. These can be implanted and fitted with customized temporary crowns in a single surgical procedure, restoring function and aesthetics and consenting recovery of the bone deficit with reduced healing times and limited patient discomfort. One-piece wide-diameter titanium screw implants with thread measurements of 2.1 and 2.6 mm (smaller diameter) up to diameter of 4.5 mm with one abutment of 2.0 and 2.5 mm respectively, were positioned and splinted by intraoral welding. One-piece titanium implants were used together with a pin (needle) titanium implant as supporting structure to achieve deep stabilization. The Scialom-like pin has a diameter of 1.2 mm and it is long enough to reach deep cortical bone that is “bicorticalism”. The One-piece implant is tightly connected to the needle implant by means of Mondani intra-oral welding technique. In severely atrophic anterior maxilla, the use of this method allows the immediate loading of a fixed resin prosthesis soon after surgery. These implants yielded satisfactory functional and aesthetic outcome in bone-deficient upper anterior sectors, without invasive regenerative procedures. The low invasiveness of this approach also consents rapid healing, reduced biological burden and greater patient benefit.

Epidemiology of chronic spontaneous urticaria: results from a nationwide, population-based study in Italy.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease, but there is a paucity of precise epidemiological data on this disease. OBJECTIVES: To obtain information on the epidemiology of CSU in Italy. METHODS: The data source was the Health Search IMS Health Longitudinal Patient Database. The study population was formed by patients aged ≥ 15 years, registered with a total of 700 general practitioners, homogeneously distributed across Italy. An algorithm based on the International Classification of Diseases, ninth revision, Clinical Modification was used for the identification of patients with CSU. The annual prevalence and incidence rates of CSU over a 12-year period (2002-2013) were estimated, along with demographic and clinical determinants. RESULTS: The annual prevalence of CSU ranged from 0·02% in 2002 to 0·38% in 2013. The incidence was 0·10-1·50 per 1000 person-years. For both prevalence and incidence rates, female patients outnumbered male. The risk of CSU was statistically significantly higher in the presence of the following variables: obesity; anxiety, dissociative and somatoform disorders; malignancies; use of immunosuppressive drugs; and chronic use of systemic corticosteroids. History of autoimmune thyroiditis showed a trend towards an increased risk of CSU, though it was not statistically significant. Smoking was associated with a significantly reduced risk of CSU. CONCLUSIONS: Our findings on CSU prevalence are consistent with those obtained in previous studies. Furthermore, this large population-based study provides important information regarding the association of CSU with demographic and clinical determinants, which have been examined in the primary-care setting.

Consensus on the use of cyclosporine in dermatological practice. Italian Consensus Conference.

Cyclosporine A (CsA) efficacy and safety have been proven in various dermatoses both in adults and in children even as long-term treatment. Over the last 25 years, Italian dermatologists have gathered relevant experience about CsA treatment for psoriasis and atopic dermatitis. This paper has been developed by an Italian Consensus Conference and it is aimed at providing recommendations based on real-world clinical experience in adult patients, consistent with efficacy and safety data arising from the scientific literature. The paper is mainly focused on the analysis of the optimal therapeutic schemes for psoriasis and atopic dermatitis, in terms of doses and treatment duration, according to individual characteristics and to the severity of the disease. Moreover, it overviews ideal management, taking into account pharmacological interactions, influence of comorbidities, and the most common adverse events related to CsA treatment.

Occupational Therapy Task Observation Scale (OTTOS) and Comprehensive Occupational Therapy Evaluation Scale (CO-TES): Italian translation, adaptation, and validation.

Background: In literature there is a lack of specific evaluation tools for behavior in intellectual disabilities in general and during an activity, this is one of the most important field of the Occupational Therapy intervention. Objective: Authors developed an Italian version of the Occupational Therapy Task Observation Scale (OTTOS) and an Italian version of the Comprehensive Occupational Therapy Evaluation Scale (COTES) and examined their reliability and validity. Methods: The original scales were translated from English to Italian using the "Translation and Cultural Adaptation of Patient Reported Outcomes Measures-Principles of Good Practice" guidelines. Both scales were administered to adults with mild and moderate intellectual disabilities. People under eighteen years, with severe and profound intellectual disabilities and deaf people were excluded from the study. Their reliability and validity have been examined. Relia-bility was analyzed via internal consistency (Cronbach's alpha) and stability (intra/inter-rater coefficient), while validity was investigated via construct validity (p-value) and criterion validity using Pearson's correlation coefficients between them and with the Mini Mental State Examination and the Barthel Index Scale. Results: The OTTOS and the COTES were administered to 30 subjects. Cronbach's α for the COTES was 0,91 and Cronbach's α for the OTTOS was 0,92. Regarding the criterion of validity, the two scales have numerous statistically positive correlations, particularly with the Mini Mental State Examination in the Orientation and total part. Furthermore, the correlation with the Barthel scale is present in the total scores, the COTES's third subscale, and the OTTOS's first. Conclusions: The OTTOS and the COTES were reliable and valid outcome measures for assessing behavior in the Italian population.

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

BACKGROUND: For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. METHODS: Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. RESULTS: Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. CONCLUSIONS: Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure.

BACKGROUND: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure. METHODS: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data. RESULTS: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2), PaO2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO2/FiO2 or PaO2 and FiO2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO2/FiO2 are predictors of intubation. CONCLUSIONS: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO2/FiO2 after starting CPAP are predictors of intubation.

Cyclosporine in transplantation - a history of converging timelines.

Discovery and pharmacological development of cyclosporine was conducted by Jean Borel and colleagues in the 1970s. Cyclosporine is the first compound to inhibit the lymphocytes specifically and reversibly, and represents the prototype of a new generation of immunosuppressive drugs: the calcineurine inhibitors. Historical chronology of successes in clinical application of cyclosporine and development of solid-organ transplantation are retraced here, underscoring the converging timelines of this drug and these interventions. In 1978-79 the first successful results of the use of cyclosporine in kidney were reported. Cyclosporine was the first single drug able to control rejection. In 1982-83 first trials demonstrated the benefit from treatment with cyclosporine in kidney recipients compared to azathioprine and steroids. In the 1980s solid-organ transplantation entered the cyclosporine era with unhoped-for results in heart transplantation. The present review focuses also on cyclosporine-based regimen of immunosuppression, adverse side effects and safety in pregnancy in subjects under treatment with cyclosporine.

Physical performance in kidney transplanted patients: a study on desert trekking.

Physical performance of kidney transplanted patients in challenging environments, such as deserts, has been poorly studied. Six kidney transplanted (T: 5 males, 1 female; 45±6 yrs) and 8 control (C: 5 males, 3 females; 49±13 yrs) subjects participated in a 5-day desert trek. Blood pressure, hydration status (Height2/Rz by bioimpedance), heart rate, energy expenditure (by SenseWear Pro Armband) and walking velocities were recorded during each daily trekking stage (GPS-assisted wearable devices). Systo-diastolic blood pressure did not differ between C (119/77±12/8 mmHg) and T (121/77±10/6 mmHg) groups throughout the study. The hydration status was stable from day 1 (Ht2/Rz: 64±13 cm2/Ohm in T and 59±12 cm2/Ohm in C subjects) to day 5 (66±11 cm2/Ohm in T and 61±13 cm2/Ohm in C subjects) in both groups. Two patients on steroid treatment showed a relative hyperhydration. Mean heart rate did not differ between T (135±10 bpm) and C (136±5 bpm) subjects throughout the study, although a reduction from day 1 to day 5 was observed in T subjects only (p<0.05 vs C group). No differences were found between T and C group in walking velocity (1.7±0.6 km/h in T and 1.7±0.5 km/h in C group); mean intensity of physical activity was 3.4±0.5 METs in T and 3.3±0.6 METs in C group during each trekking stage. Negligible differences were observed in cardiovascular, metabolic and hydration status adaptations to desert trekking between selected T and C individuals. T subjects with creatinine clearance > 55 ml/min showed acceptable physical performance and acclimatization to desert environment, suggesting a good long-term outcome of transplantation.

Abdominal volume contribution to tidal volume as an early indicator of respiratory impairment in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterised by progressive loss of muscular strength that leads to an increasingly restrictive pulmonary syndrome. However, it is still not clear whether this determines alterations in the breathing pattern. We studied: 66 DMD patients at different stages of the disease (mean+/- sem age 12.6+/-0.6 yrs, range 5-22 yrs of age), subdivided into four groups according to age; and 21 age-matched healthy male controls. Spirometry, lung volumes and nocturnal oxygen saturation were measured in all DMD patients. Ventilatory pattern and chest wall volume variations were assessed by optoelectronic plethysmography during spontaneous breathing both in seated and supine positions. Whilst in a seated position, no significant differences were found between patients and controls or between different age groups. In the supine position, the average contribution of abdominal volume change (DeltaV(AB)) to tidal volume progressively decreased with age (p<0.001). The patients who showed nocturnal hypoxaemia showed significantly lower Delta V(AB). In conclusion, chest wall motion during spontaneous breathing in awake conditions and in supine position is an important indicator of the degree of respiratory muscle impairment in DMD. DeltaV(AB) is not only an important marker of the progression of the disease but is also an early indicator of nocturnal hypoxaemia.

Bioavailability of Sandimmun® versus Sandimmun Neoral®: a meta-analysis of published studies.

For the past 25 years, cyclosporine A (CyA) has played a pivotal role in transplant immunosuppressant therapy. From the availability of the 2 primary marketed formulations (Sandimmun® and Sandimmun Neoral®, Novartis), confusion has existed with regard to whether these two formulations are bioequivalent. Due to the underlying clinical relevance of this information, we therefore conducted a meta-analysis of all available comparative pharmacokinetic studies to assess whether the two different CyA formulations, Sandimmun® and Sandimmun Neoral®, can be considered bioequivalent. All clinical studies that compared the bioavailability of the 2 formulations in organ transplant recipients were considered for analysis. We searched computerised databases (Embase/Excerpta Medica and Medline/PubMed) from their inception to May 2010. Only studies with AUC values determined at 12 hours were considered for analysis. Relative bioavailability was calculated with 90 percent confidence intervals (CI) for Sandimmun® (test substance) versus Sandimmun Neoral® (reference substance) according to Schuirmann?s Two One-Sided Tests Procedure and the Classical Shortest CI. Homogeneity of data was tested using the Χ(2) test. Fifteen studies were considered for meta-analysis and none of these studies reported AUC values in the 80-125 percent range required for the bioequivalence of two formulations. The overall bioavailability for Sandimmun® versus the microemulsion formulation Sandimmun Neoral® was 76 percent, with upper CI limits lower than 80 percent in some cases. Mean AUC values for Sandimmun® were significantly lower than those for Sandimmun Neoral® (p<0.01). This study demonstrates that the 2 main cyclosporine formulations, Sandimmun® and Sandimmun Neoral®, cannot be considered bioequivalent.

Clinical outcome evaluation following cyclosporine a treatment in moderate to severe psoriasis: a retrospective study.

This retrospective study was conducted on 193 patients treated in three Italian Psoriasis Units with the aim of evaluating the evolution of psoriasis severity and the safety of cyclosporin A (Sandimmun Neoral) in moderate to severe psoriasis, at the regimens usually employed in common clinical practice. Cyclosporin A (CyA) was administered for a mean period of 14 months, the mean number of treatment courses was 1.6 (range 1-4), and the mean dosage ranged from 1.5 to 3.1 mg/kg/die. Ninety percent of patients obtained complete therapeutic success or clinical remission, defined as complete clearance of lesions or clearance of lesions with residual minor pigmentations respectively, when treated with CyA in monotherapy. The mean Psoriasis Area and Severity Index (PASI) decreased from 23.31 before CyA administration to 5.64 at the end of treatment. The clinicians judgement on CyA tolerability was good/very good in 90 percent of cases. Adverse events occurred in 36 percent of patients, with hypertension being the most commonly reported (17.6 percent). The results of this study indicate that in the common clinical practice CyA in moderate to severe psoriasis is usually employed at low doses, resulting both safe and effective.

Psoriasis relapse evaluation with week-end cyclosporine A treatment: results of a randomized, double-blind, multicenter study.

Cyclosporine A (CsA) effectively controls psoriasis, however, its long-term continuous use is not recommended. This study aims to evaluate the efficacy and tolerability of week-end CsA microemulsion for the reduction of relapse rate in patients with chronic plaque psoriasis who had achieved clinical remission following continuous CsA therapy. The PREWENT (Psoriasis Relapse Evaluation with Week-End Neoral Treatment) study was a 24 week, randomized, double-blind, multicenter study, carried out in 22 Italian hospital or University Dermatology units. CsA was discontinued for 8 days previous to the patients being randomized to oral CsA 5 mg/kg/day or placebo for two consecutive days/week, for a total period of 24 weeks. The primary endpoint was clinical success rate at week 24, defined as the proportion of patients with no clinical worsening (no relapse or a Psoriasis Area and Severity Index (PASI) < 75 percent of pre-treatment PASI). A total of 162 patients were randomized to CsA and 81 to placebo. Clinical success rates at 24 weeks were 66.9 and 53.2 percent with CsA and placebo, respectively (p = 0.072). Time to first relapse was significantly prolonged with CsA versus placebo (p = 0.023), and PASI was significantly lower from weeks 4 to 16 in CsA recipients. In patients with moderate-severe psoriasis, the clinical success rate was significantly increased with CsA compared to placebo (69.9% vs 46.3%; p = 0.011), and significantly lower increases in PASI were observed from week 4 to week 24 (p < 0.05 vs placebo). CsA was well tolerated, with no differences in mean blood creatinine or blood pressure between CsA and placebo recipients. However, the high withdrawal rate (22.2% of randomized patients), which was not related to side effects, may have led to an overestimation of efficacy, but the study had a good statistical power (88% greater than that observed in similar studies, i.e. 80%). Week-end CsA administration was shown to prolong safely and effectively the time to first relapse in psoriasis patients.

Evolution of and risk factors for psychological distress in patients with psoriasis: the PSYCHAE study.

Psychological distress (PD) is common in patients with psoriasis but little is known about its evolution. The aim of this study is to assess the evolution of PD in psoriasis. For this purpose, 1,505 psoriatic patients, who had been previously enrolled in the PSYCHAE study, an observational multicenter Italian study, were re-evaluated after 6 and 12 months. Minor and major PD were assessed using the General Health Questionnaire (GHQ) and Brief Symptoms Inventory (BSI) questionnaires and coping using Brief COPE questionnaire. Minor PD was present in 46 percent of patients but halved during the study. Female gender, surface area, topical steroids, methotrexate, self-distraction, venting and behavioral disengagement were risk factors for minor PD; cyclosporine and humor were protective. Major PD was present in 11 percent of patients and remained stable. Female gender, venting, religion, behavioral disengagement and emotional support were risk factors for major PD; instrumental support was protective. In conclusion, the results obtained suggest that major PD remained stable after 12 months and that coping was a predictor of its evolution.

Explorative analysis of gender-specific characteristics in patients with heart failure in an Italian hospital.

Sex-related differences have been shown to deeply affect health-related aspects of patients. However, the lack of gender-specific analysis makes it difficult to advance personalized medicine in terms of a gender-based approach. The aim of the present study was to describe gender-specific features of patients diagnosed with heart failure (HF), with a focus on the clinical presentation. Data were collected from a properly designed database and referred to an Italian hospital. Patients aged ≥18 years with a primary or secondary diagnosis of HF between 1 January 2012 and 31 December 2016 were included, and their demographic and clinical characteristics were analyzed according to gender. Of the 719 HF patients included, 317 (44.1%) were male and 402 (55.9%) were female. Women tended to be older compared to men (82.4±8.8 years and 77.1±10.6 years, respectively). As for clinical presentation, 62.1% of female and 38.3% of male patients had preserved ejection fraction, and 56.1% of men and 58.2% of women suffered from atrial fibrillation. The left atrium was partially compromised in 62.4% of male and 63% of female patients, while right atrium dysfunction tended to be more frequent in male patients compared to female patients (29.1% and 25.5%, respectively). In conclusion, gender-specific features of a cohort of HF patients from a clinical setting were accurately described.

Psoriasis and the risk of acute coronary syndrome in the elderly.

BACKGROUND: Psoriasis has been associated with a higher prevalence of cardiovascular disease risk factors. However, there is inadequate quantification on the association between psoriasis and acute coronary syndrome (ACS), particularly in the elderly. Therefore, the aim of the present study was to assess the risk of ACS according to history of psoriasis in subjects aged 75 years and older. METHODS: We carried out a case control study based on 1455 cases and 1108 controls. Cases were all the patients admitted in the randomized Elderly ACS 2 trial. Controls were selected from subjects aged ≥75 years included in the Prevalence of Actinic Keratoses in the Italian Population Study (PraKtis), based on a representative sample of the general Italian population. Odds ratios (OR) of ACS according to history of psoriasis were obtained using a multiple logistic regression model including terms for age, sex and smoking. RESULTS: The prevalence of psoriasis was lower among cases (12/1455, 0.8%) than among controls (18/1108, 1.6%). The multivariate OR of ACS according to history of psoriasis was 0.51 (95% confidence interval: 0.23-1.09). CONCLUSIONS: Our data does not support an association between psoriasis and risk of ACS in the elderly.

Diazabicyclo analogues of maraviroc: synthesis, modeling, NMR studies and antiviral activity.

Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction power, whereas the diazabicyclononane was less effective. Biological data were rationalized through a computational study that allowed the conformational preferences of the compounds to be determined and a correlation between the inhibitory activity, the bridge length of the bicycle, and the rotational barrier around dihedral angle τ7 to be hypothesized. A high-field NMR analysis supported the modeling results.

Effect of chestnut tannin on fermentation quality, proteolysis, and protein rumen degradability of alfalfa silage.

Two experiments were conducted on alfalfa to investigate the effects of the addition of commercial chestnut hydrolyzable tannin at ensiling on 1) silage fermentation quality in lab-scale silos and protein degradation in the rumen, and 2) silage fermentation quality and proteolysis in bale silages. Wilted alfalfa was prepared with 4 tannin levels (0, 2, 4, and 6% on a dry matter (DM) basis; T0, T1, T2, T3, respectively) and ensiled in lab-scale silos. Silages (33% DM) were analyzed for fermentation quality, protein rumen degradability in situ, and organic matter digestibility in vitro through gas production after 120 d of conservation. Wilted alfalfa containing 0 and 4% tannin (T0 and T2) was harvested at 40% DM (wilting level I) and 53% DM (wilting level II) for bale (600 mm diameter) silage. Silages were analyzed for fermentation quality after 78 d of conservation. All the silages were well fermented with no butyric acid. Lab-scale silages showed reductions in ammonia, nonprotein nitrogen (NPN) and DM losses in T2 and T3 treatments, while the fermentation acid profiles were unaffected. In experiment 1, the untreated silage (T0) had the highest protein degradability after being incubated in the rumen. The addition of tannin reduced crude protein ruminal disappearance in a dose-dependent manner. However, the tannin reduced the organic matter digestibility by 5.1% for all of the tannin addition levels. The tannin positively affected the silage quality in the round bale silages, in particular reducing ammonia and NPN in the lowest wilting level. In both experiments, T2 treatment reduced proteolysis without any influence of DM on the binding reaction and reduced the NPN by 15% in comparison to the control.