Analysis of session-RPE and profile of mood states during a triathlon training camp.

AIM: The aim of the present study was to monitor the internal training load and profile of mood states (POMS) during a training camp in junior-elite triathletes. METHODS: Sixteen (10 male and 6 female) young triathlon athletes (junior-elite: 18±1 yrs) were included in this study. All triathletes had been training for 7±3 years, and regularly trained 4 times a week 3h per session, throughout the year. The training camp (5 days) included two daily supervised training sessions. The CR-10RPE scale was used 30 minutes after every training session to evaluate session-RPE. POMS was administered 3 times during the training camp: at the beginning, on the 3rd day, and at the end of training camp. RESULTS: Session-RPE throughout the different training days showed significant differences (P<0.001). POMS scores showed a significant increase (P<0.001) in fatigue from the first (7.8±1.4), to the third (10.5±2.2) and to the last day of training (14.2±3.4). At the end of the camp, lower (P<0.01) vigour values (12.7±2.8) emerged with respect to the first day (15.8±3.0), whereas anger decreased (P=0.015) the last day (8.6±2.2) with respect to the intermediate evaluation (9.6±2.7). CONCLUSION: The 45% increase in fatigue, the 24% decrease in vigour, and the intraindividual variability in session RPE that emerged, indicates that young triathletes need to be monitored closely during training camps in order to individualize training to avoid training maladaptation such as non-functional overreaching.

Parental attitude toward children's oral health during COVID-19 pandemic: a cross-sectional study in Italy.

AIM: During the COVID-19 pandemic, restrictive rules were imposed around the world to limit the spread of the virus. The present study aims to investigate how the pandemic and the consequent restrictions have affected the lives and oral health of Italian families with children aged 0-14 years. MATERIALS: Through a questionnaire distributed online from December 2020 to March 2021 the following aspects were investigated: family income during the pandemic, fear of the pandemic, dietary habits, perceived risk of infection in a dental practice and perceived children oral health status during the pandemic. CONCLUSION: The pandemic has not drastically changed the socio-economic conditions, the dietary habits and the oral health condition of most Italian children. Nevertheless, the pandemic seems to have highlighted significant macro-regional differences regarding the satisfaction with the response of the regional health services to the pandemic. The continuation of the pandemic and the possible socio-economic effects could favour new changes in lifestyles, oral health and discrepancies regarding health care access, which deserve to be the subject of further investigation.

Catalytic mechanism of l,l-diaminopimelic acid with diaminopimelate epimerase by molecular docking simulations.

Peptidoglycan, a key constituent of bacterial cell walls, is currently the target of broad spectrum antibiotics and a new research field involves both design and synthesis of inhibitors of its biosynthesis. Most bacteria require either lysine, or its biosynthetic precursor, diaminopimelate (meso-DAP), as a component of the peptidoglycan layer of the cell wall. In this paper, molecular modelling studies were undertaken in order to shed light on the molecular basis of interaction between (2S,6S)-diaminopimelic acid (l,l-DAP) (1) with its target enzyme DAP-epimerase, since this is a key step in the lysine biosynthetic path leading to (2R,6S)-diaminopimelic acid (meso-DAP) (2). In particular, the docking of the ligand-enzyme complex was studied by means of MD simulations and DFT computations in order to ascertain the optimal structural requirements for the epimerization reaction. Molecular dynamics simulations clearly showed that the configuration of the distal carbon C6 of l,l-DAP is critical for complex formation since both amino and carboxylate groups are involved in Hbonding interactions with the active site residues. Furthermore, the interactions occurring between the functional groups bonded to the C2 and some residues of the binding cavity immobilize the ligand in a position appropriate for the epimerization reaction, i.e., exactly in the middle of the two catalytic residues Cys73 and Cys217 as confirmed by DFT quantum mechanical computation of the Michaelis complex. All this mechanistic information could be useful for the rational design of new potential antibiotic drugs effective as inhibitors of peptidoglycan biosynthesis.

Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro.

Dopamine (DA) and somatostatin (SRIF) receptor agonists inhibit growth hormone (GH) secretion by pituitary adenomas. We investigated DA subtype 2 receptor (DR2) and SRIF receptor (sst) subtypes 2 and 5 expression in 25 GH-secreting pituitary adenomas and tested in primary culture the effects on GH and prolactin (PRL) secretion of sst agonists selectively interacting with sst2 (BIM-23120), sst5 (BIM-23206), and sst2 and sst5 (BIM-23244). All adenomas expressed sst2; eight adenomas expressed both sst5 and DR2, eight sst5 but not DR2, and eight DR2 but not sst5. One tissue lacked expression of DR2 and sst5. GH secretion was inhibited by BIM-23120 in all samples, while it was reduced by BIM-23206 only in adenomas not expressing DR2. BIM-23120's inhibitory effects correlated with sst2 and DR2 expression, whereas DR2 expression correlated inversely with BIM-23206 inhibitory effects on GH secretion. In seven mixed GH-/PRL-secreting pituitary adenomas, PRL secretion was inhibited in sst5-expressing tumors by BIM-23206, but not by BIM-23120. BIM-23244 reduced PRL secretion only in adenomas expressing sst2, sst5 and DR2. sst5 and DR2 expression correlated directly with BIM23206 inhibitory effects on PRL secretion. Our results suggest that adenomas expressing DR2 are less likely to respond to clinically available SRIF analogs in terms of GH secretion inhibition. Therefore, drugs interacting also with DR2 might better control secretion of pituitary adenomas.

Quantum mechanical analysis of oxygenated and deoxygenated states of hemocyanin: theoretical clues for a plausible allosteric model of oxygen binding.

In this work with ab initio computations, we describe relevant interactions between protein active sites and ligands, using as a test case arthropod hemocyanins. A computational analysis of models corresponding to the oxygenated and deoxygenated forms of the hemocyanin active site is performed using the Density Functional Theory approach. We characterize the electron density distribution of the binding site with and without bound oxygen in relation to the geometry, which stems out of the crystals of three hemocyanin proteins, namely the oxygenated form from the horseshoe crab Limulus polyphemus, and the deoxygenated forms, respectively, from the same source and from another arthropod, the spiny lobster Panulirus interruplus. Comparison of the three available crystals indicate structural differences at the oxygen binding site, which cannot be explained only by the presence and absence of the oxygen ligand, since the geometry of the ligand site of the deoxygenated Panulirus hemocyanin is rather similar to that of the oxygenated Limulus protein. This finding was interpreted in the frame of a mechanism of allosteric regulation for oxygen binding. However, the cooperative mechanism, which is experimentally well documented, is only partially supported by crystallographic data, since no oxygenated crystal of Panulirus hemocyanin is presently available. We address the following question: is the local ligand geometry responsible for the difference of the dicopper distance observed in the two deoxygenated forms of hemocyanin or is it necessary to advocate the allosteric regulation of the active site conformations in order to reconcile the different crystal forms? We find that the difference of the dicopper distance between the two deoxygenated hemocyanins is not due to the small differences of ligand geometry found in the crystals and conclude that it must be therefore stabilized by the whole protein tertiary structure.

Diagnostic performance of a new highly sensitive thyroglobulin immunoassay.

The determination of serum thyroglobulin (Tg) is commonly used for detecting the presence of residual thyroid tissue or cancer recurrence in patients treated for differentiated thyroid cancer (DTC). The aim of the study was to evaluate the performance characteristics of a recently introduced fully automated chemiluminescent immunoassay, based on four monoclonal antibodies and which produces results in 40 min. Analytical sensitivity (0.01 micro g/l) was computed from 20 replicates of the zero calibrator and of the 'Tg-free' sample pool. Functional sensitivity (0.1 micro g/l at 20 coefficients of variation percent) was determined from the imprecision profile obtained by assaying ten serum pools. The reliability of the measurements in the low concentration range (Tg<1 micro g/l) has been checked by progressive dilution with the 'Tg-free' serum of a sample pool at 5.27 micro g/l; measured values were very close to the expected values (recovery 100-133%).Cut-off at the 99th percentile in DTC stage I 'disease-free' treated patients (n=53) was 0.16 micro g/l. Tg measurement in basal conditions during L-thyroxine suppression therapy and 5 days after recombinant human TSH stimulation was performed in 22 patients with DTC. In 80% of patients with basal Tg<0.1 micro g/l (12/15), Tg remained<0.1 micro g/l after stimulation, and in all of these Tg was<1 micro g/l. Our results have indicated the optimal analytical and clinical performance of this Tg immunoassay and encourage further studies on larger populations of patients with DTC.

Zirconium tetrachloride-formaldehyde sigma-complexes: A computational and spectroscopic investigation

We have carried out a combined theoretical-experimental study of the structures and energies of ZrCl(4)-aldehyde complexes using (13)C NMR spectroscopy and a DFT (B3LYP) computational approach. The computational investigation has demonstrated the existence of different types of complexes: a 1:1 complex (H(2)CO-ZrCl(4)), various 2:1 complexes ((H(2)CO)(2)-ZrCl(4)), and several dimeric species. The analysis of the energies involved in the formation of the various complexes has indicated that the dimeric species should correspond to the only adduct observed in the (13)C NMR spectra (carbonyl resonance at 226.96 ppm) when a 1:1 ZrCl(4)/aldehyde molar ratio is used, while the 2:1 complex should be responsible for the signal at 224.30 ppm that is recorded when this molar ratio is 1:2.

Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.

[Immunoblastic sarcoma: considerations on a recently observed case]. / Il sarcoma immunoblastico: considerazioni su un caso di recente osservazione.

Supervening immunoblastic sarcoma in a patient with congenital immune deficiency is described. The literature suggests that this sarcoma may be a hyperimmune form similar to the GVHR described by Frizzera and the question whether or not angioimmunoblastic lymphadenopathy had previously occurred in the present case is discussed. The part played by the spleen and the effect of splenectomy on the progression of the disease are also examined.

[Hemorrhagic rectocolitis. Attempt at programmed therapy]. / Retto colite emorragica. Tentativo di terapia programmata.

Planned treatment of 30 cases of haemorrhagic colitis is reported. Its protocol included salazopyrine and benzodiazepine per os, salazopyrine and prednisone per rectum, and parenteral ACTH depot. Administration for 60 days brought good results in cases of slight or average severity. Recurrences, albeit less severe, were not prevented, however. Attention is drawn to the need to follow up this group of patients for a longer period. Even so, it is felt that the effect of this form of treatment is primarily symptomatic.

Resistance and reactance in patients undergoing coronary artery bypass.

PURPOSE: The purpose of this study was to evaluate the effect of different surgical variables, such as perfusion duration and number of grafts, on resistance and reactance, in heart surgery patients. METHODS: 77 patients submitted to coronary artery bypass were studied. The variable concerning time of extracorporeal circulation was classified in four progressive degrees. Resistance and reactance measurements were performed and compared to time of extracorporeal circulation and to number of grafts. Ten measurements were performed by bioelectrical impedance equipment. RESULTS: The comparison of reactance before surgery to the first measurement at the first postoperative day, for the different times of extracorporeal circulation, showed decrease (p = 0.01). Regarding gender, resistance and reactance showed significant differences (p < 0.001). There was also significant difference (p = 0.001) for the number of grafts. CONCLUSION: The decrease of resistance and reactance is related not only with surgery procedure, but also with the number of grafts and time of extracorporeal circulation.

[Survey on antibiotic prescriptions in general medicine]. / Indagine sulla prescrizione di antibiotici in medicina generale.

The objectives of the survey are to describe the use of antibiotics in general practice, in order to identify inappropriate use and to estimate the exposure to different antibiotic categories in the population. The data refer to the overall drug prescriptions issued in general practice during 1991 in Rome. Four million of antibiotic prescriptions were issued, corresponding to 9% of the overall drug prescriptions and to 11% of the drug expenditure in Rome. When considering all anti-infective drugs (antibiotics plus antivirals and immunostimulating agents) the prescriptions and the expenditure increase up to 13% and 18% respectively. Three therapeutic categories (penicillins, cephalosporins and macrolides) represent more than 50% of the antibiotic prescriptions. Among the general population, 34% received at least one anti-infective drug and each patient received on average 2.7 prescriptions during the year. More than 20% of the prescriptions refers to antibiotic categories (such as aminoglycosides and chloramphenicols) which are not considered as a first choice in general practice. The analysis shows that a considerable proportion of antibiotic prescriptions refers to therapeutic categories with negative benefit/risk profile. More appropriate use of antibiotics might reduce both adverse events and drug expenditure.

[Clinical and monitoring experience of isotretinoin in Italy]. / Esperienze cliniche e di monitoraggio dell'isotretinoina in Italia.

We report the results of a multicentric evaluation on effectiveness and safety of isotretinoin in severe acne, recalcitrant to traditional treatments. 208 patients, suffering especially from cystic acne, have been enrolled in a post-marketing clinical trial in 11 Dermatological Italian Departments. The clinical effectiveness of isotretinoin has been very good in 77% of patients, good in 16% and sufficient in 4%. The tolerability of the drug was considered good in 90% of patients. Finally, isotretinoin might be considered as one of the most effective drugs in the therapy of severe forms of acne, resistant to usual treatment, and often affecting patients on the physical and psychological side.

miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222.

Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.

3-bromozinc propenyl esters: an experimental and theoretical study of the unique stereocrossover observed in their addition to aromatic and aliphatic aldehydes.

We report the results of a combined experimental and theoretical study on the reaction of 3-bromopropenyl acetate in the presence of zinc with three different aldehydes (i.e., benzaldehyde, 2-methylpropanal, and cyclohexanecarboxaldehyde). A 80% de in favor of the anti product has been experimentally observed with both saturated aldehydes, while for benzaldehyde, a 1:1 syn/anti ratio has been found. DFT computations show the existence of three eta1-allylic organozinc complexes [gamma-(Z)-5a, gamma-(E)-5a, and alpha-5a], very close in energy. Only gamma-(Z)-5a and gamma-(E)-5a lead to the observed product. The computational investigation of the reaction of these allylic organozinc complexes with benzaldehyde and 2-methylpropanal demonstrates in both cases the existence of two competitive reaction paths leading to the syn and anti adducts, respectively. An anti preference has been found for 2-methylpropanal with both gamma-(Z)-5a and gamma-(E)-5a species (a diastereoselectivity larger than 80% is predicted), in agreement with the experiment. With benzaldehyde, while the reaction of gamma-(Z)-5a retains an anti-stereopreference (de = 70%), that involving gamma-(E)-5a is characterized by two degenerate transition states. In this case, the agreement between computations and experiments would be satisfactory under the assumption that the initial oxidative addition affords the gamma-(E)-5a zinc complex only. Additional MP2 computations have demonstrated that pi-stacking interactions can play a significant role in determining the relative energy of the transition states leading to the syn and anti products.

Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer.

OBJECTIVE: Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/metastases after treatment for differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly sensitive Tg assay during routine follow-up of DTC patients. DESIGN: Tg values were measured by a highly sensitive Tg assay during L-T4 suppressive therapy and after recombinant human thyrotropin (rh-TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay. PATIENTS: One hundred and sixty consecutive DTC-treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied. MEASUREMENTS: Measured variables included neck ultrasonography, (131)I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA). RESULTS: During L-T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut-off of 2 microg/l after rh-TSH, a negative response was associated with undetectable Immulite Tg during L-T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L-T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively. CONCLUSIONS: The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC-treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh-TSH test.

Cutaneous adverse reactions following the administration of nonsteroidal antiinflammatory drugs and antibiotics: an Italian survey.

The Italian Group for Epidemiological Research in Dermatology (GISED) collected a series of cutaneous adverse reactions following NSAID and/or antibiotics administered by topical and/or systemic route. Dermatologists from North and Central Italy took part in this survey by filling in 1457 case report forms during a four-month observation time in 1988-89. The main purpose of our epidemiological study aimed at evaluating a post-marketing surveillance program by examining spontaneous reports of cutaneous adverse reactions. This result seems to be noteworthy, considering the difficulties encountered in Italy to develop such a program.