Dupilumab-associated ocular adverse events are predicted by low tear break-up time and correlate with high IL-33 tear concentrations in patients with atopic dermatitis.

Dupilumab, blocking IL-4 and IL-13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab-treated patients with moderate-to- severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate-to-severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty-nine patients with moderate-to-severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL-33 tear fluid levels and a significantly lower tear break-up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management.

Dietary supplements, drugs and doping in the sport society.

Consumption of supplements and the use/abuse of drugs to support athletic performance is increasingly growing. The aim of this paper is to approach the phenomenon by providing a tool to develop critical awareness of these problems. By reviewing scientific articles, we collected information on the use of licit and illicit substances among professional and non-professional athletes, showing a widespread scenario also based on false myths. The use of supplements, drugs and doping substances represents a complex and still debated issue, that deserves greater consideration among both sportsmen and health operators. A more critical and informed approach to these topics can support empowerment and a conscious use of drugs by respecting eating habits, own health and healthy lifestyles.

Erice 2018 Charter on the role of the National Health Service in the prevention of doping

The Erice 2018 Charter was unanimously approved at the conclusion of the 53rd Residential Course of the International School of Epidemiology and Preventive Medicine "Adapted Physical Activity in Sport, Wellness and Fitness; the role of the Departments of Prevention and of the National Health Service in doping prevention and health promotion", held on 15-19 May 2018 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the Study Group on "Movement Sciences for Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The event was part of a larger project supported by the Ministry of Health aimed at preventing doping in the general population involved in sport and physical activities. After an intense discussion the participants focused on ten statements involving the following critical issues: responsibility, priority, message, alphabetization, networks and alliances, school promoting health, player and opportunities, competences, know-how, programming and acting. These statements provide hints to approach doping within a public health frame and summarize the role of the Departments of Prevention and NHS in promoting and coordinating preventive actions with other institutions and stakeholders. Doping represents a complex phenomenon related to cultural, social, economic and legal issues. In addition to regulatory or repressive actions, education to health and legality is proposed as the fundamental strategy to contrast doping by promoting healthy lifestyles, based on scientific knowledge and respect for legality.

Peer Education strategies for promoting prevention of doping in different populations.

BACKGROUND: In the field of doping prevention, alongside the traditional functions of repression and control of the phenomenon, educational aspects are becoming increasingly important. Article 18 of the World Anti doping Code obliges the signatories to invest in anti-doping education with the aim of preserving the spirit of sport. The educational commitment should involve young people in health promotion interventions for the prevention of risk behaviors. Therefore, our attention has focused on finding the mechanisms that lead people to make certain behavioral choices. MATERIAL AND METHODS: In the context of preventive programs, to counter the doping phenomenon through health promotion programs, the most recognized method is peer education, particularly with adolescents. It is an educational method according to which some members of a group are empowered and trained to carry out specific activities with their peers. It is constituted as an example of equal relationship and finds its basis in cooperation and solidarity with the aim of increasing empowerment and a healthy development of the identity and collective dimension in young people. RESULTS: Numerous experts - biologists / nutritionists, hygienists, sports coaches, psychologists, teachers of physical education in secondary schools and other stakeholders have actively participated in the co-construction of a training package aimed at activating cascade training processes on the knowledge and skills of peer education in contexts of youth aggregation, such as schools, gyms, sports associations, social gatherings of all kinds. The path allowed to define a peer education model capable of enabling the participants to activate health promotion interventions for the prevention of doping risk behaviors, each in their own setting. CONCLUSIONS: In conclusion, we can say that prevention programs are the more effective the more they are addressed to young people and adolescents and provide interactive and action-oriented interventions. Successful initiatives aim to emphasize the development of life skills and to influence numerous determinants of behavior, including individual attitudes, knowledge, motivations, interpersonal relationships and social norms. If the aim is to act on the change of behavior, the efforts will be more successful if the content of the intervention will give due consideration to the context in which it applies and the target population, involving it and addressing its specific needs and values.

The prevention of doping and the improper use of drugs and food supplements in sports and physical activities: a survey on the activity of the prevention departments of Italian local health authorities.

INTRODUCTION: Doping is an important public health problem widespread not only among elite athletes, but also among amateur and recreational athletes and the general population. In Italy the introduction of doping prevention within the Essential Levels of Care (LEA) with the DPCM 12/1/2017 represents a crucial step towards the implementation of education and health promotion interventions. In this context, the Departments of Prevention (DP) of the Local Health Authorities (LHA) have to play a fundamental role, becoming the cultural and operational reference on this issue. As part of the "Doping prevention: development of a permanent educational tool coordinated by the National Health Service Prevention Departments" project, funded by the Italian Ministry of Health, a survey was conducted on the activities carried out by the DP regarding doping prevention and improper use and abuse of drugs and food supplements in sports and physical activities, as a basis for the harmonization of organizational structures and prevention programs and the creation of a collaboration network at a regional and national level. METHODS: A semi-structured questionnaire consisting of 11 questions, prepared on an electronic platform, was sent to the DP of all the Italian LHA. RESULTS: A total of 38 DP out of 131 (29%) completed the questionnaire, with representation from all regions. 42.1% of DP carried out or are still running programs for the prevention of doping, a percentage that decreases to 27% considering the programs for the prevention of misuse and abuse of drugs and food supplements in sports and in physical activities; in less than half of the DP, 37.5% and 41.7%, respectively, dedicated funds have been allocated. The professionals most involved in prevention of doping are the Specialists in Sport Medicine (81.3%) followed by Specialists in Hygiene (43.8%) and Psychologists (37.5%), while Health Care Assistants (50%) are the professionals most involved in the prevention of the improper use of drugs and food supplements, followed by Specialists in Hygiene and Specialists in Sport Medicine (40%). Most of the DP (71.9%) believe that the introduction of programs to prevent and counteract doping in the LEA will have repercussions on their approach against doping. CONCLUSIONS: The survey, although conducted on a limited sample, has provided an important framework relating to programs for the prevention of doping and the misuse and abuse of drugs and food supplements in sports and in the physical activities carried out by DP. A remarkable heterogeneity has been highlighted, both at national and regional level. It is urgent to provide DP with homogeneous and effective organizational models and adequate operational tools, paying particular attention to the training of all the professionals involved. It is also essential to implement permanent monitoring tools.

Intraorbital injection of rituximab: a new approach for active thyroid-associated orbitopathy, a prospective case series.

AIM: The aim of this paper was to examine the efficacy and the safety of intraorbital administration of the monoclonal anti-CD20 antibody rituximab (RTX) to treat patients affected by thyroid-associated orbitopathy (TAO) unresponsive to conventional therapy. METHODS: Five patients with active moderately-severe TAO unresponsive to systemic glucocorticoids were studied. After a complete ophthalmological examination, disease activity and severity were assessed by the clinical activity score (CAS) and the NO SPECS scoring system. Computed tomography scans were performed in all patients. Patients were treated with intraorbital injection of RTX 10 mg once a week for one month repeated once one month apart. The patients were followed every three months until 18 months. RESULTS: In all patients treated with RTX, CAS was significantly reduced (p< 0,005), inactive phase of TAO was reached in four out of five patients. No patients experienced major side effects, minor side effects were reported in two patients. CONCLUSION: Intraorbital injection of RTX is a safe and useful promising therapeutic option for active TAO.

Does ABS ensure good performance in emergency braking for less skilled motorcyclists?

This study aims to investigate whether motorcyclists are able to use the full potential of anti-lock braking systems (ABS) in demanding braking situations that maintain the natural coupling of action and perception of emergency events, or whether instead the lack of braking skills in riders makes ABS almost ineffective and comparable to non-ABS brakes on dry pavement. Six experienced riders performed two experimental tests. First test included 12 emergency braking trials in a realistic scenario using a mock-up of an intersection conflict with a car initiating a left turn manoeuvre across the path (LTAP) of a motorcycle approaching from the opposite direction as an unpredicted moving hazard. Second test included three trials in a planned self-timed hard braking. The speed at the onset of braking was 35-45 km/h. The braking performance was measured from the initiation of brake pressure until the full stop of the vehicle. Front wheel ABS usage was determined by the pressure in the master cylinder and wheel callipers. The testing resulted in 85 data runs with full stop braking manoeuvres. Results revealed four categories of riders classified by their front wheel ABS usage during the emergency braking tests, which included two riders who underused front wheel ABS (9.6% and 27.4% of braking time on average). The worst case resulted in a significantly longer braking distance (braking deceleration of 5.2 m/s2). The highest skilled rider, who reached initial jerks close to 30 m/s3, used the ABS of the front wheel 93.7% of the braking time on average, resulting in a braking deceleration of 7.71 m/s2. Overall, the best braking performance was achieved in trials where the front ABS was activated for more than 80% of the braking. In planned self-timed hard braking test, where riders have more time to plan the braking manoeuvre, the experience rider with lowest performance during the emergency braking test improved braking efficiency and was able to increase ABS activation from 9.6% to 26.8% of the time, achieving a deceleration of 6.24 m/s2. ABS is demonstrated to reduce stopping distances and to improve stability under all braking conditions, but such features are not enough to guarantee a good braking performance in emergency events if the riders have not the skills to utilize the full braking power of the motorcycle. Less skilled riders, even with ABS, may not have the confidence to increase braking power further when reaching high decelerations that push them to the limit of their stabilisation control in emergency braking, thus increasing braking distance with potentially life-threatening consequences. Our results suggest that many experience riders still need knowledge and skill to make the ABS work to its optimum in emergency events to avoid crashes. Further research with larger sample sizes including the full diversity of the motorcyclist population is recommended to determine the actual proportion of motorcyclists underusing ABS.

[Case-mix index and length of hospitalization]. / L'indice di case-mix e la durata della degenza.

The ACG (Adjusted Clinical Groups) case-mix system is a classification method of diseases of patients, focused on the person. Depending on the pattern of these morbid conditions, the ACG system assigns each patient to a single group (an ACG group), which allows to capture the effects of a group of diseases in estimates of resource use. Diseases are classified into a diagnostic group (ADG) according to 5 clinical dimensions: duration (acute, recurrent or chronic), severity (minor/major vs stable/unstable), diagnostic assessment (symptoms vs diseases), etiology (infectious, traumatic or other), specialty (medical, surgical, obstetric, ...). All diseases can be classified into these dimensions and into one of 32 groups. The ACG case-mix system uses an algorithm to classify each patient into one of 93 ACG categories. Each person is assigned to an ACG according to his ADG combination, his age and his gender. With the repayment system "case-mix", surgery has become central for all great hospitals in virtue of its great productive potential. The case-mix index is one of the factors which influence the duration of hospitalization. The case-mix system has emphasized the importance of the duration of hospitalization, encouraging the planning of programs in order to discharge patients early after surgical operations. It has also stimulated the surgical activity in operating units with "budget" forecasts in which resources are provided according to an expected level of specialist surgery.

[Micromedullary thyroid carcinoma: school experience]. / Il microcarcinoma midollare della tiroide: esperienza di Scuola.

Medullary microcarcinomas occurrence are rare and fortuitous, it's usually related to the calcitonin measurement, that's the gold standard for the diagnosis. In other cases performing a thyroidectomy for a benign thyroid disease it's found a sub-centimeter tumor. Actually it's not clear the most appropriate surgical treatment for those kind of tumors because the number of cases in literature is limited and because there are different surgical approaches. In this study 17 patients were operated for medullary thyroid microcarcinoma and the Authors found central lymph node metastases in 33.3% of cases. The Authors, analyzing those results, think that total thyroidectomy with lymphadenectomy of the central compartement is the best choice in a sporadic microcarcinoma, while a total thyroidectomy without lymphadenectomy should be performed when the microcarcinomas are incidentals.

[Two cases of synchronous papillary and medullary thyroid carcinoma]. / Due casi di carcinomi tiroidei sincroni di tipo midollare e papillifero.

The Authors describe two cases of simultaneous association of papillary and medullary thyroid carcinoma. They emphasize the treatment of these cases stressing the correlation between the therapeutic criteria and the malignancy of medullary carcinoma.

[Medullary thyroid carcinoma: a study about 28 operated patients]. / Carcinoma midollare della tiroide: studio su 28 casi operati.

In this study on 28 operated patients, the Authors show that total thyroidectomy with elective central neck dissection and ipsilateral neck dissection is the most appropriate surgical treatment for medullary thyroid carcinoma. Pathologic study on lymph nodes removed in central and in latero-cervical compartments showed malignancy respectively in 75% and in 70% of the cases. However the role of elective ipsilateral lateral neck dissection remains controversial.

[Retroperitoneal giant mixed sarcoma. Case report]. / Un caso di sarcoma misto retroperitoneale gigante.

The Authors present a rare case of voluminous retroperitoneal tumor in a 41 years old woman. CT scan showed a solid abdominal expansive mass, with compression and displacement of the left lobe of the liver, spleen, stomach, pancreas, and left kidney. The patient underwent surgery for excision of a giant retroperitoneal mass. Surgery was uneventful. The patients recovered well. Histology showed a mixed liposarcoma and angiosarcoma with high grade of malignancy and positivity for vimentin, factor VIII, CD34, CD31 and negativity for S-100, CD68, AMS, AML. The prognosis of these tumours is closely related to local recurrence, histological type, size and radical surgery. A low-grade malignancy tumor, small sized and completely resected leads to a good prognosis. Radiation therapy and chemotherapy do not seem to have a strong influence on the prognosis. An aggressive surgical approach is the first choice for the treatment of such tumors. The resection of adjacent organs may be required for radical surgery.

Complete amino-acid sequence of PD-S2, a new ribosome-inactivating protein from seeds of Phytolacca dioica L.

The primary structure has been determined for PD-S2, a new type 1 ribosome-inactivating protein (RIP), isolated from the seeds of Phytolacca dioica L. PD-S2 has 265 amino-acid residues, and a molecular mass of 29586 Da. The polypeptide chain contains four amino-acid residues more than PAP-S, a type-I RIP isolated from the seeds of the taxonomically related plant Phytolacca americana L. We have compared the amino-acid sequence of PD-S2 with those of two other RIPs with known three-dimensional structure: PAP-S and ricin A-chain (RTA), the active chain of the best known type-2 RIP. This analysis shows an identity of 76% and 33% with PAP-S and RTA respectively, and a similarity of 82% and 54%. Comparison with the PAP sequence, isolated from leaves of P. americana, shows an even higher identity (80%) and similarity (87%). Furthermore, the amino-acid residues reported in other RIPs to be invariant and participate in the definition of the active site (Tyr-76, Tyr-127, Glu-179, Arg-182 and Trp-211; PD-S2 numbering) are all present. Asn-74, Arg-138, Gln-175, and Glu-208 are also conserved, while Asn-209 is substituted by Glu, all residues located in the active-site cleft of RIPs (Tahirov, T.H., Lu, T.-H., Liaw, Y.-C., Chen, J.L. and Lin, J.Y. (1995) Crystal structure of abrin-a at 2.14 A, J. Mol. Biol. 250, 354-367). The polypeptide chain of PD-S2 contains two N-glycosylation sites at Asn-112 and Asn-120, the second of which appears to be linked to sugars. Like PAP-S, PD-S2 does not contain free sulfhydryl groups. The four cysteinyl residues of the two proteins have corresponding sequence positions, most likely with identical S-S pairing.

Archaeal elongation factor 1 beta is a dimer. Primary structure, molecular and biochemical properties.

The elongation factor 1 beta (EF-1 beta), that in eukarya and archaea promotes the replacement of GDP by GTP on the elongation factor 1 alpha x GDP complex, was purified to homogeneity from the thermoacidophilic archaeon Sulfolobus solfataricus (SsEF-1 beta). Its primary structure was established by sequenced Edman degradation of the entire protein or its proteolytic peptides. The molecular weight of SsEF-1 beta was estimated as about 10000 or 20000 under denaturing or native conditions respectively; this finding suggests that the native protein exists as a dimer. The peptide chain of SsEF-1 beta is much shorter than that of its eukaryotic analogues and homology is found only at their C-terminal region; no homology exists between SsEF-1 beta and eubacterial EF-Ts. At 50 degrees C, at a concentration of SsEF-1 beta 5-fold higher than that of SsEF-1 alpha x [3H]GDP the rate of the exchange of [3H]GDP for GTP becomes about 160-fold faster. An analysis of the values of the energetic parameters indicates that in the presence of SsEF-1 beta the GDP/GTP exchange is entropically favoured. At 100 degrees C the half-life of SsEF-1 beta is about 4 h.

Purification and partial characterization of a mitogenic lectin from the latex of Euphorbia marginata.

A lectin was purified from the latex of Euphorbia marginata by affinity chromatography on acid-treated Sepharose 6B and elution with lactose. The lectin is a glycoprotein composed of two identical subunits with M(r) 30,000, approx. The haemagglutinating activity of the lectin is not specific for any human blood group, and is inhibited by galactose and galactose-containing sugars and by gentiobiose. The lectin is strongly mitogenic for human T-lymphocytes and induces the release of interleukin-1 beta and tumor necrosis factor-alpha from cultured mononuclear cells.

Pharmacokinetics of a new extended-release nifedipine formulation following a single oral dose, in human volunteers.

This study aimed to define the pharmacokinetics of nifedipine following oral administration of a new extended-release formulation. Twelve healthy volunteers of both sexes, aged 39 +/- 4 years, were treated with a single oral tablet of a new extended-release formulation containing 40 mg of nifedipine. Samples of venous blood were taken before dosing, after 30 min and at 1, 2, 4, 8, 12, 16, 20 and 24 h after administration. Nifedipine concentration was measured by means of a high-performance liquid chromatography method. Noncompartmental pharmacokinetics parameters were then calculated. The plasma concentration of nifedipine increased slowly and in seven subjects biphasic peaks occurred. The mean values were as follows: t(max): 8.5 +/- 1.2 h; C(max): 36.55 +/- 6.76 ng/ml; AUC: 347.06 +/- 51.61 ng/h/ml; AUC 409.99 +/- 61.08 ng/h/ml; A(half-life): 2.26 +/- 0.36 h; D(half-life): 2.43 +/- 0.44 h; E(half-life): 4.62 +/- 0.79 h. Twenty-four hours after administration nifedipine was still detectable (3.17 +/- 0.67 ng/ml). Arterial blood pressure decreased and heart rate increased concurrently and proportionally to the increase in nifedipine concentration. Extended-release nifedipine formulations have better tolerability profiles than immediate-release formulations, which are at present not recommended in the treatment of hypertension, hypertensive crises or myocardial infarction. This new extended-release formulation has interesting pharmacokinetic parameters and may be effective in conditions in which dihydropyridine calcium channel blockers are indicated.

Sexual behaviour in untreated and treated coeliac patients.

BACKGROUND: Sexual behaviour is often altered in chronic illness. AIM: To evaluate sexual behaviour in coeliac patients before and after treatment with a gluten-free diet. PATIENTS: Fifty-five adults with coeliac disease and 51 age- and sex-matched healthy controls. METHODS: Routine clinical and laboratory work-up was used for diagnosis of coeliac disease. Age of first sexual intercourse, prevalence of individuals who were sexually active, frequency of intercourse, reduction in sexual desire, difficulty in attaining orgasm, pain during intercourse, and prevalence of individuals defining themselves as satisfied with their sexual life were investigated by an anonymous, self-administered questionnaire administered before and after one year's treatment with a gluten-free diet in coeliac patients, and only once in controls. Analyses included clinical conditions, demographic and socio-economic data. RESULTS: Compared with controls, untreated coeliac patients had a significantly lower frequency of intercourse and a lower prevalence of individuals satisfied with their sexual life. Patients with overt and subclinical coeliac disease did not show significant differences for any indices of sexual behaviour. Compared with untreated conditions, coeliac patients after one year of treatment had improved values for all indices of sexual behaviour: differences were significant for frequency of intercourse and prevalence of individuals satisfied with their sexual life. CONCLUSION: Untreated coeliac disease, even in its subclinical presentation, is associated with disorders in sexual behaviour which are improved by the dietary treatment.

Ventricular fibrillation-defibrillation in the toad Bufo paracnemis.

Fibrillation is more likely to occur in animals showing a high degree of cellular differentiation. Lower species, with cardiac tissue histologically and electrophysiologically more uniform, very rarely, if ever, can fall into this uncoordinated activity. We describe experiments during which two specimens of the South American toad, Bufo paracnemis (body weights, 363 g and 297 g; ventricular weights, 1.8 g and 1.4 g, respectively), were repeatedly fibrillated and defibrillated almost at will. However, we failed when we tried a series of experiments in a given number of animals. Over a total of 16 fibrillation-defibrillation episodes, a fibrillation threshold of about 3.8 mA/g was estimated. The lowest defibrillation values were, respectively, 43 mA/g and 507 mA/g, using rectangular pulses (less than 7 msec pulses width). There were also a few spontaneous reversals before and after defibrillation shocks. These cases point to our still poor understanding of the mechanisms involved in the process. It is suggested that reentry or multiple ectopic foci might not be the basic mechanisms, as traditionally accepted. Rather, it might well be a new behavior of the cells or group of cells like that predicted by the theory of deterministic chaos.

Isolation and primary structure determination of a metallothionein from Paracentrotus lividus (Echinodermata, Echinoidea).

A low-molecular-mass zinc-binding protein was purified from the eggs of the sea urchin Paracentrotus lividus using procedures that included gel-permeation and anion-exchange chromatography followed by HPLC. The primary structure of this protein was derived from the sequences of peptide fragments obtained by digestion with trypsin and thermolysin. The reconstructed sequence showed the presence of 20 cysteinyl residues, thus resembling that of a metallothionein. The Paracentrotus protein was most similar to the metallothionein of Strongylocentrotus purpuratus, another member of the order of Echinoida, living along the coast of the Pacific Ocean. However, the presence of non-conservative amino acid substitution, together with a deletion of two residues in the Strongylocentrotus metallothionein, make the similarity scores of the two sea urchin proteins lower than that of metallothioneins from vertebrates of the same order. In addition, the present data show that sea urchin metallothioneins display no homology with metallothioneins of any other species.

The role of ocular oscillations upon visually dependent postural stabilization in patients affected by congenital nystagmus.

Visually dependent postural stabilization decreases as a consequence of a long-standing reduction of visual cues in patients affected by congenital nystagmus. The aim of the present study was to verify whether the changes in postural control in this group of patients are due to ocular oscillations or to reduced visual acuity. Therefore, postural control was evaluated when the nystagmus was blocked by the blocking position or by prisms and compared with the postural score observed in a group of normal controls whose visual acuity had been artificially reduced to the same level as that of the patients using Bangerter's filters. The results show a statistically significant improvement of visually dependent postural stabilization when ocular oscillations are inhibited either by the gaze blocking position or by prisms. They also show that postural control in normal subjects with Bangerter's filters is reduced, but is still significantly better than that observed when ocular oscillations are inhibited in patients affected by congenital nystagmus. Our data strongly support the role of ocular oscillations in visually dependent postural control, since postural impairment recovered under any condition in which ocular oscillations were abolished, despite differences in visual acuity. Our data also show that reduced visual acuity decreases visually dependent postural control to a lesser degree than ocular oscillations. This could be due to the fact that ocular oscillations are a disturbing input, usually inhibited centrally, in order to avoid oscillopsia. This mechanism is probably responsible for the reduced role of visual cues in the postural control in this group of patients. The reduction of visual acuity, by comparison, merely causes a decrease in visual cues, depending on the degree of visual loss. It can be concluded that the impaired postural control in patients affected by congenital nystagmus is mainly due to ocular oscillations, with reduced visual acuity creating a secondary effect.