Adoptive Immunotherapy With Tumor-Infiltrating Lymphocytes and Subcutaneous Recombinant Interleukin-2 Plus Interferon Alfa-2a for Melanoma Patients With Nonresectable Distant Disease: A Phase I/II Pilot Trial

Background: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-2a), for patients with metastatic melanoma.Methods: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6–18 × 10⁶ IU/m²/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-2a was administered subcutaneously at 3 × 10⁶ IU three times each week until progression.Results: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 × 10⁹ (range, 1–43 × 10⁹), and the median period of culture was 52 days (range, 45–60). rIL-2 was administered at doses ranging between 6 and 18 × 10⁶ IU/m²/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2–35%).Conclusions: Outpatient treatment with TIL plus rIL-2 and rIFN-2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.     

Daytime course of sleepiness in de novo Parkinson's disease patients

Normal subjects show an increase of sleepiness in the morning, early afternoon and before sleep. In the advanced stages of Parkinson's disease (PD) the mean level of sleepiness is quite high, while with respect to healthy subjects it seems to be unchanged in the early stages. The aim of this study was to evaluate the time–course of the sleepiness level during the wakefulness period in untreated patients with early‐stage Parkinson's disease. Eighteen Parkinson's disease patients who had never been treated before with dopaminergic drugs (male = 9, female = 9, age: 68.39 ± 1.89, mean ± standard error) and 18 healthy subjects (male = 9, female = 9, age: 67.22 ± 1.98) were recruited for this study. All subjects underwent continuous actigraphic recording for three consecutive days, during which they also completed the Karolinska Sleepiness Scale (KSS) once an hour throughout wakefulness. Our results showed a higher level of sleepiness in the patients than the controls in the hours following awakening and in the early afternoon, specifically at 08:00 and 14:00 hours (08:00 hours, PD patients, KSS: 3 ± 0.3 versus healthy subjects, KSS: 2 ± 0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 ± 0.5 versus healthy subjects, KSS: 3 ± 0.3, P < 0.05). We suggest that some daytime hours are sensitive windows showing the first increase of sleepiness which will spread later to the whole daytime.     

Awareness of complications and maintenance mode of oral piercing in a group of adolescents and young Italian adults with intraoral piercing

Background

The aim of the study was to focus the awareness of complications of oral piercing among a group of adolescents and young Italian adults with intraoral piercings.

Material and Methods

A total of 225 teenagers were asked to complete a questionnaire on the awareness of complications of oral piercing. An additional questionnaire was administered in case of oral piercing worn, based on site piercing, knowledge about piercer license, oral and systemic risks due to oral piercing, disinfection and sterilization of the material pierced, information by the piercer about piercing hygiene maintenance and post-piercing dentist check-up. After questionnaire all partecipants received a brochure with some information about risks and maintenance mode of piercing.

Results

Data revealed that more than 50% of teens surveyed was found to wear a piercing. Only 25.3% was aware of the risk of HCV cross-infection and only 17.3% reported of knowledge about risk of endocarditis. Only 17% checked the piercer license and only 18% sterilization and disinfection of the materials used. 53.7% did not received explanations about the risks associated with piercing. With regard to the maintenance mode of the piercing, it has been suggested to brush the piercing bar in 17% of cases. The post piercing specialist visits have been suggested only in 7% of cases.

Conclusions

The general lack of awareness of complications and maintenance mode related to oral piercing needs to be addressed by some education programs performed at school and by dentists. Key words: Oral piercing, oral health, oral complications.     

A Comparison between Endodontics and Implantology: An 8‐Year Retrospective Study

Purpose: The aim of this study was to compare endodontic and implant treatments and to evaluate their predictability over an 8‐year period on the basis of an analysis of survival data and a retrospective clinical study. Materials and Methods: A group of 40 partially edentulous patients were selected for this study. Their teeth had been endodontically treated and rehabilitated using gold alloy and ceramic restorations. In these patients, 65 osseointegrated implants were restored with single gold alloy–ceramic crowns and monitored on a yearly basis for 8 years with standardized periapical radiographs, using a polivynilsiloxane occlusal key as a positioner. A total of nine patients who did not attend the yearly follow‐up were excluded from the study. The Melloning and Triplett criteria were used to evaluate the clinical results obtained in the implant sites. The clinical results of the 56 endodontically treated teeth, restored with the fixed prosthesis of 40 patients, were analyzed according to probing depth as well as an assessment of the correct apical and coronal seals. The survival rate was calculated using the Kaplan–Meier method and the statistical significance was calculated using the chi‐square test. Results: During the follow‐up of the endodontically treated elements, seven failures were detected (83.34%) and the success rate of implants inserted in the same patients was equal to 80.8%, with nine implants lost in 8 years. The survival analysis of the elements treated with both therapies was not statistically significant (p = .757) and the confidence interval was between 0.2455 and 2.777. Conclusion: In view of the superimposable results between the two therapies, it should be noted that the endodontically treated teeth could be interested by different pathologies while the restoration of the atrophic edentulous ridge with an implant support is predictable when patients comply with correct oral hygiene and when the occlusal loads are axially distributed in implant‐protected occlusion.     

Automated Classification of 6-n-Propylthiouracil Taster Status with Machine Learning

Several studies have used taste sensitivity to 6-n-propylthiouracil (PROP) to evaluate interindividual taste variability and its impact on food preferences, nutrition, and health. We used a supervised learning (SL) approach for the automatic identification of the PROP taster categories (super taster (ST); medium taster (MT); and non-taster (NT)) of 84 subjects (aged 18–40 years). Biological features determined from subjects were included for the training system. Results showed that SL enables the automatic identification of objective PROP taster status, with high precision (97%). The biological features were classified in order of importance in facilitating learning and as prediction factors. The ratings of perceived taste intensity for PROP paper disks (50 mM) and PROP solution (3.2 mM), along with fungiform papilla density, were the most important features, and high estimated values pushed toward ST prediction, while low values leaned toward NT prediction. Furthermore, TAS2R38 genotypes were significant features (AVI/AVI, PAV/PAV, and PAV/AVI to classify NTs, STs, and MTs, respectively). These results, in showing that the SL approach enables an automatic, immediate, scalable, and high-precision classification of PROP taster status, suggest that it may represent an objective and reliable tool in taste physiology studies, with applications ranging from basic science and medicine to food sciences.     

Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.     

Randomised study for the 1-year crestal bone maintenance around modified diameter implants with different loading protocols: a radiographic evaluation

This study evaluated by standardised digitised periapical radiography the crestal bone maintenance around modified diameter internal hex implants with variable thread design and narrow neck loaded with different procedures. Forty implants were placed in 25 patients. Twenty implants were conventionally loaded, 20 ones immediately loaded. Radiographs were taken with a customised bite record and processed with software. Measurements of bone from the fixture–abutment junction to mesial and distal marginal bone levels were made. Student’s t test statistical analysis was adopted. Baseline data were variable; at 1-year follow-up, there were no significant differences for marginal bone loss between immediately and conventionally loaded maxillary implants (p = 0.1031), whilst there were slight significant differences between immediately and conventionally loaded implants in the mandible (p = 0.0141). Crestal bone maintenance around conventionally and immediately loaded modified diameter implants was similar, with slight significant differences in mandible where a lower marginal bone loss was observed.