The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.

BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.

Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study.

BACKGROUND: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies. PATIENTS AND METHODS: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided α and ß errors of 0.05 and 0.20, 47 patients per group were needed. RESULTS: Forty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P = 0.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showed microsatellite instability (P < 0.001). CONCLUSION: The investigated panel of genomic alterations allows refining the selection of RAS and BRAF wild-type metastatic colorectal cancer patients candidates for anti-EGFRs, partially explaining and further corroborating the predictive ability of primary tumour sidedness.

[The Carnot efficiency and plant photosystems].

The concept that the Carnot efficiency places an upper limit of 0.60-0.75 on the thermodynamic efficiency of photosynthetic primary photochemistry is examined using the PSI-LHCI preparation. The maximal quantum efficiency was determined approximately 0.99 which yielded a thermodynamic efficiency of 0.96, a value far above that predicted on the basis of the Carnot efficiency. The commonly presented reasoning leading to the Carnot efficiency idea was therefore critically examined. It is concluded that the crucial assumption that the pigment system, under illumination, is in equilibrium with the incident light field, at a black body temperature of Tr, is erroneous, as the temperature of the excited state pigments was experimentally shown to be that of the sample solvent (thermal bath), 280 K in this case. It is concluded that the classical reasoning used to describe the thermodynamics of heat systems is not applicable to "photonic" systems such as plant photosystems.

Impact of ablation index settings on pulmonary vein reconnection.

PURPOSE: Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is still debated. We evaluated the incidence of acute and late PV reconnection (PVR) with different AI settings and its predictors. METHODS: The Ablation Index Registry is a multicenter study that included patients with paroxysmal/persistent atrial fibrillation (AF) who underwent first-time ablation. Each operator performed the ablation using his preferred ablation catheter (ThermoCool® SmartTouch or Surround Flow) and AI setting (380 posterior-500 anterior and 330 posterior-450 anterior). We divided the study population into two groups according to the AI setting used: group 1 (330-450) and group 2 (380-500). Incidence of acute PVR was validated within 30 min after PVI, whereas the incidence of late PVR was evaluated at repeat procedure. RESULTS: Overall, 490 patients were divided into groups 1 (258) and 2 (232). There was no significant difference in the procedural time, fluoroscopy time, and rate of the first-pass PVI between the two study groups. Acute PVR was observed in 5.6% PVs. The rate of acute PVR was slightly higher in group 2 (64/943, 6.8%, PVs) than in group 1 (48/1045, 4.6% PVs, p = 0.04). Thirty patients (6%) underwent a repeat procedure and late PVR was observed in 57/116 (49%) PVs (number of reconnected PV per patient of 1.9 ± 1.6). A similar rate of late PVR was found in the two study groups. No predictors of acute and late PVR were found. CONCLUSION: Ablation with a lower range of AI is highly effective and is not associated with a higher rate of acute and late PVR. No predictors of PV reconnection were found.

The in-ear region as a novel anatomical site for ECG signal detection: validation study on healthy volunteers.

PURPOSE: Early detection of cardiac arrhythmias is a major opportunity for mobile health, as wearable devices nowadays available can detect single-lead electrocardiogram (ECG). The study aims to validate the in-ear region as a new anatomical site for ECG signal detection and looks towards designing innovative ECG wearable devices. METHODS: We performed ECG using KardiaMobile device (AliveCor®) on 35 healthy volunteers. First, ECG was detected by standard modality using both hands. Then, ECG was detected using the left in-ear region instead of the right hand. All the recorded ECGs were analyzed by the device and by two cardiologists in blind testing. RESULTS: We successfully collected 70 ECGs performed on 35 volunteers (male 54%, age 39.1 ± 10.7 years; BMI 22.9 ± 2.89 kg/m2) with no differences observed by KardiaMobile in ECG reports detected in the two different modalities. All the ECGs were reported as normal by the device and the two cardiologists. Moreover, linear regression analysis showed good correlation between the amplitude (mV) of P (r = 0.76; r2 = 0.57; p < 0.0001) and QRS waves (r = 0.81; r2 = 0.65; p < 0.0001), the intervals (ms) of PR (r = 0.91; r2 = 0.83; p < 0.0001; LOA - 0.60-0.41; CC = 0.91), QRS (r = 0.78; r2 = 0.61; p < 0.0001; LOA - 0.49-0.43; CC = 0.78), QT (r = 0.85; r2 = 0.71; p < 0.0001; LOA - 1.31-1.20; CC = 0.85), and heart rate (r = 0.94; r2 = 0.89; p < 0.0001; LOA - 7.82-7.76; CC = 0.94) detected in two different modalities. CONCLUSION: The in-ear region is a reliable novel anatomical site for ECG signal detection in normal healthy subjects. Further studies are needed to validate this new ECG detection modality also in case of cardiac arrhythmias and to support the development of new wearable devices.

Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study.

INTRODUCTION: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study. METHODS: Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS). RESULTS: Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS = 0.01/0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS = 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P = 0.02), PFS2 (P = 0.01), and OS (P = 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio = 0.60; P = 0.03) and mixed subtypes (hazard ratio = 0.44; P = 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study. CONCLUSIONS: We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab.

2D/3D accuracies of implant position after guided surgery using different surgical protocols: A retrospective study.

PURPOSE: To compare the 2D and 3D positional accuracy of four guided surgical protocols using an analysis of linear and angular deviations. METHODS: DICOM and .STLs files obtained from a CBCT and a digital impression were superimposed with software to plan implant position. Fifty-six patients were subdivided into 4 groups: FGA group (template support [Ts]: teeth [T]; bed preparation [Bp]: fully guided [FG]; implant insertion [Ii]: 3D template [3Dt]; device [D]: manual adapter [MA], FGM group (Ts: T; Bp: FG; Ii: 3Dt; D: fully guided mounter [FGM]), PG group (Ts: T; Bp: FG; Ii: manual; D: none) and MS group (Ts: mucosa; Bp: FG; Ii: 3Dt; D: FGM). The position of 120 implants was assessed by superimposing the planned and final position recorded with a digital impression. RESULTS: In FGA group, 3D deviations were 0.92 ± 0.52 mm at the implant head and 1.14 ± 0.54 mm at the apex, and the angular deviation (ang. dev.) was 2.45 ± 1.24°. In FGM group, were 0.911 ± 0.44 mm (head) and 1.11 ± 0.54 mm (apex), and the ang. dev. was 2.73 ± 1.96°. In PG group, were 0.95 ± 0.47 mm (head) and 1.17 ± 0.488 mm (apex), and the ang. dev. was 3.71 ± 1.67°. In MS group, were 1.15 ± 0.45 mm (head) and 1.42 ± 0.45 mm (apex), and the ang. dev. was 4.19 ± 2.62°. Ang. dev. of MS group was different from the other groups (P < 0.05). CONCLUSIONS: Guided surgery showed a sufficient accuracy.

Hand and ultrasonic instrumentation in combination with root-coverage surgery: a comparative controlled randomized clinical trial.

BACKGROUND: The role of vigorous root planing in the surgical treatment of gingival recession was recently questioned. The aim of the present randomized controlled split-mouth clinical study was to compare the effectiveness, in terms of root coverage, of hand and ultrasonic root instrumentation in combination with a coronally advanced flap for the treatment of isolated-type recession defects. METHODS: Eleven systemically and periodontally healthy subjects with bilateral recession defects (> or = 3 mm) of similar (< or = 1 mm) depth affecting contralateral teeth were enrolled in the study. Only Miller Class I gingival recession with no deep cervical abrasion or root caries/demineralization were included in the study. Control root exposures were treated with curets, whereas test roots were instrumented with ultrasonic piezoelectric devices. Randomization for test and control treatment was performed by a coin toss immediately prior to surgery. All recessions were treated with a coronally advanced flap surgical technique. The clinical reevaluation was made 6 months after surgery. RESULTS: The two approaches resulted in a high percentage of root coverage (95.4% in the control group and 84.2% in the test group) and complete root coverage (82% in the control group and 55% in the test teeth), with no statistically significant difference between them. Clinical attachment level gains were clinically significant in both groups (3.36 +/- 0.92 mm in the control group and 2.90 +/- 0.70 mm in the test group), with no statistically significant difference between them. The increase in keratinized tissue height was statistically significant in both groups (0.55 +/- 0.52 mm in the control group and 0.36 +/- 0.67 mm in the test group), with no difference between them. CONCLUSIONS: The present study failed to demonstrate any superiority, in terms of root-coverage results, for hand instruments over ultrasonic treatment of the root surface in combination with coronally advanced flap mucogingival surgery. Further studies of longer-term duration and larger sample size could help to establish the superiority of one form of root instrumentation in conjunction with root-coverage surgery.

Coronally advanced flap with and without vertical releasing incisions for the treatment of multiple gingival recessions: a comparative controlled randomized clinical trial.

BACKGROUND: Vertical releasing incisions might damage the blood supply to the flap and result in unesthetic visible white scars. The aim of the present study was to compare root coverage and esthetic outcomes of the coronally advanced flap (CAF) with and without vertical releasing incisions in the treatment of multiple gingival recessions. METHODS: Thirty-two systemically and periodontally healthy subjects with esthetic complaints due to the exposure of Miller Class I and II multiple (at least two) gingival recession defects (> or =1 mm) affecting adjacent teeth of the same quadrant of the upper jaw were enrolled in the study. Sixteen patients (with 45 gingival recessions) were randomly assigned to the control group, and the other 16 patients (with 47 recession defects) were assigned to the test group. All recessions were treated with a CAF; vertical releasing incisions were performed in the control group, whereas an envelope-type flap was used in the test group. The patient's postoperative morbidity was assessed 1 week after the surgery, whereas the esthetic evaluation, made by the patient and independent periodontist, and the clinical evaluation were made 1 year later. RESULTS: Surgical time was significantly shorter in the envelope-type CAF group. No statistically significant difference was demonstrated between the two groups in terms of recession reduction and clinical attachment level gain. A statistically greater probability of complete root coverage (adjusted odds ratio, 3.76; 95% confidence interval: 0.92 to 15.33; P <0.05) and a greater increase in buccal keratinized tissue height were observed with the envelope type of CAF. Patient satisfaction with esthetics was very high in both treatment groups, with no statistically significant differences between them. A better postoperative course and better results in the esthetic evaluation made by an independent periodontist were demonstrated in patients treated with the envelope type of CAF. CONCLUSIONS: Both CAF techniques were effective in reducing recession depth. The envelope type of CAF was associated with an increased probability of achieving complete root coverage and with a better postoperative course. Keloid formation along the vertical releasing incisions was responsible for the worst esthetic evaluation made by an independent expert periodontist.

Performance and clinical comparison between left ventricular quadripolar and bipolar leads in cardiac resynchronization therapy: Observational research.

AIM: To evaluate Attain Performa (Medtronic, Dublin, Ireland) quadripolar lead performance in clinical practice and, secondarily, to compare its long term clinical outcomes vs bipolar leads for left ventricular (LV) pacing. METHODS AND RESULTS: We retrospectively analyzed clinical, procedural and follow-up data of 215 patients implanted with a quadripolar lead. One hundred and twenty one patients implanted with bipolar lead were selected to compare long-term clinical outcomes. The quadripolar lead was implanted in the target vein in 196 patients (91%) without acute dislodgements. In 50% of patients the chosen final pacing configuration at implant would not have been available with bipolar leads. A dedicated quadripolar pacing vector was chosen more frequently when the LV tip location was apical than otherwise (65.6% vs 42.7%, p=0.003). After a median follow-up of 14 months, the LV pacing threshold was less than 2.5V at 0.4ms in 98 patients (90%) with a safety margin between phrenic nerve and LV pacing threshold >3V in 97 patients (89%). We observed a slight trend toward a lower risk of heart failure worsening and a lower incidence of ventricular arrhythmias and pulmonary congestion in patients implanted with quadripolar leads compared with the control group. CONCLUSION: Quadripolar leads improve the management of phrenic nerve stimulation at no trade-off with pacing threshold and lead stability. Quadripolar leads seems to be associated with a lower incidence of VT/VF and pulmonary congestion, when compared with bipolar leads, but further investigations are necessary to confirm that this positive effect is associated with better LV reverse remodeling.

Serum thyroglobulin measurement: clinical background and main methodological aspects with clinical impact.

It is worldwide recognized that circulating thyroglobulin (Tg) measurement represents a fundamental tool in the follow-up of patients affected by differentiated thyroid cancer (DTC). In the last American and European Consensus Conferences, a surveillance guideline has been extended to the use of thyrotropin (TSH)-stimulated Tg levels for thyroidectomized patients without clinical evidence of residual tumor with Tg below 1 microg/l during TSH suppression. Therefore, sensitivity of the methods is critical to detect small amounts of Tg and/or to observe minimal changes in Tg concentration in the management of DTC patients. It has been proposed that only methods providing the greatest distinction between the lower limit of euthyroid reference range (approximately 3.0 microg/l) and the functional sensitivity limit (at least 1 microg/l) of the assay may offer a suitable clinical sensitivity for detecting small amounts of functioning thyroid tissue in TSH-suppressed state (1 g of normal thyroid tissue results in a serum Tg of approximately 1 microg/l when TSH is normal and about 0.5 microg/l when TSH is suppressed). In the last 30 years sensitivity of Tg measurements has been greatly improved, nowadays methods can achieve very good analytical and functional sensitivity to give reliable results also in the very low concentration range (between 0.1 and 1 microg/l). In addition, with the introduction of fully automated assays, results can be readily available to the clinician while patients are still in the ambulatory area. However, despite the large clinical use of Tg measurement, wide differences (by threefold) still remain between results produced in different laboratories due to poor standardization, heterogeneity of circulating Tg, interference from auto-antibodies, differences in the epitope recognition by antibodies used in the assays.

Role of superoxide dismutase in vascular inflammation and in coronary artery disease.

Superoxide dismutase (SOD) is reported to be the major enzymatic defence against free radicals and common oxidants. EC-SOD is the only extracellular form of SOD present at a high concentration in vascular intima. The aims of the present study were to elucidate the role of EC-SOD in patients with coronary artery disease (CAD) and evaluate its association with free radicals, inflammation and with the severity of the disease. The study included 36 consecutive subjects with CAD being treated in the Institute of Clinical Physiology (33 males, 3 females) and 19 controls (16 males, 2 females). Each subject, after cardiac catheterisation and coronariography, was evaluated for serum EC-SOD activity, peroxy radicals, high-sensitive interleukin-6 (hs-IL-6), high-sensitive tumour necrosis factor (hs-TNFa) and high-sensitive C-reactive protein (hs-CRP) serum levels. The analysis of EC-SOD serum activity did not show any particular difference between patients and controls, while the serum levels of peroxy radicals, hs-IL-6 and hs-CRP showed a significant difference between the two groups (respectively: P<0.01, P<0.001, P<0.01). Moreover, enhancement of hs-IL-6 serum levels was also observed in severe disease (involvement of 3, 4 coronary arteries; P<0.05), while EC-SOD activity showed a slight increment in association with the number of arteries involved. hs-IL-6 concentrations were statistically significantly associated with peroxy radicals and CRP levels (respectively: P<0.05, r2=0.1; P<0.05, r2=0.14). The present study suggests a low effectiveness of EC-SOD activity in prevention against CAD and further confirms hs-IL-6 as a useful marker in diagnostic prevention and in clinical characterisation of CAD.

Clinical and anatomical factors limiting treatment outcomes of gingival recession: a new method to predetermine the line of root coverage.

Complete root coverage is not always achievable, even in gingival recession with no loss of interproximal attachment and bone. The cemento-enamel junction is the most widely used referring parameter to evaluate root coverage results. The aim of the present study was to describe the most frequent diagnostic mistakes that may lead to incomplete root coverage in Miller Class I and II gingival recessions and to suggest a method to predetermine the level/line of root coverage in non-molar teeth. The line of root coverage (i.e., the level/line to which the soft tissue margin will be positioned after the healing process of a root coverage surgical technique) was predetermined by calculating the ideal vertical dimension of the interdental papilla of the tooth with the recession defect. This method was applied to 120 recession-type defects affecting non-molar teeth of 80 young healthy subjects that were treated with root coverage surgical procedures over the last 5 years. All recessions were Miller Class I or II and were associated with at least one of the following characteristics: 1) traumatic loss of the tip of the interdental papilla(e); 2) tooth rotation; 3) tooth extrusion with or without occlusal abrasion; and 4) a cervical abrasion defect with no evidence of the cemento-enamel junction. The line of root coverage may be considered the clinical cemento-enamel junction because it may substitute the anatomic cemento-enamel junction when this is no longer clinically visible on the tooth with recession or when the ideal conditions to obtain complete root coverage are not fully represented.

The effect of excited state population in photosystem II on the photoinhibition-induced changes in chlorophyll fluorescence parameters

The photoinhibition-induced changes in Photosystem II fluorescence parameters of spinach thylakoids were only slightly sensitive to the excited state population in Photosystem II antenna, as modulated by either quinone quenching or energy spillover. The possibility that this may be due to a small fraction of chlorophyll molecules which are poorly coupled to the antenna is discussed.

Long-term outcome following treatment of multiple Miller class I and II recession defects in esthetic areas of the mouth.

BACKGROUND: Multiple recession defects can be successfully treated using envelope-type coronally advanced flaps. The aim of the present study was to evaluate the long-term (5 years) stability of clinical outcomes achieved with the surgery and the association between patient variables and long-term stability. METHODS: Seventy-three Miller Class I and II gingival recessions affecting 22 young, systemically healthy subjects were treated with coronally advanced flaps with no releasing incisions. All patients were instructed to perform a coronally directed roll technique to minimize the toothbrushing trauma to the gingival margin. The clinical reevaluation was made 1 year after the surgery. At this point, 13 patients took part in a supportive periodontal care program consisting of oral hygiene instructions, control of toothbrushing technique, and professional tooth cleaning every 4 months. The remaining nine patients did not participate and received only sporadic care by general dentists. At 5 years post-surgery, all patients were reexamined. RESULTS: At the 5-year examination, 94% of the root surfaces initially exposed due to gingival recession were still covered with soft tissue, and 85% of the treated recession defects showed complete coverage. Complete root coverage in all recessions was maintained in 15 out of 22 patients (68%). The long-term stability of the soft-tissue margin in the treated sites was significantly influenced by the patient's regular participation in the recall program and the susceptibility to gingival recession in other areas of the mouth. A statistically significant increase of keratinized tissue (0.80 +/- 0.64 mm) was observed between the 1- and 5-year observation visits, and the average increase of keratinized tissue between the baseline and the 5-year follow-up amounted to 1.38 +/- 0.90 mm. This increase was significantly affected by the baseline keratinized tissue (KT) and recession (REC) depth: in particular, the 5-year increase in the amount of keratinized tissue was greater in sites with a greater recession depth and lower amount of keratinized tissue at baseline. CONCLUSIONS: 1) The successful root coverage results obtained with the coronally advanced flap for multiple recession defects were well maintained over the 4-year observation period. 2) Negative patient characteristics such as a lack of compliance with a supportive care program and individual susceptibility to gingival recession were significantly associated with the recurrence in gingival recession. 3) The increase in keratinized tissue height that followed the coronally advanced flap procedure may be attributed to the tendency of the mucogingival line to regain its genetically determined position.

Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma.

Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.

Involvement of uncoupled antenna chlorophylls in photoinhibition in thylakoids.

Evidence is presented, by means of both fluorescence and action spectroscopy, that a small, spectroscopically heterogeneous population of both Chl a and Chl b molecules is present in isolated spinach thylakoids and is active in photoinhibition. The broadness of the action spectrum suggests that degraded or incompletely assembled pigment-protein complexes may be involved.

The quenching of photosystem II fluorescence does not protect the D1 protein against light induced degradation in thylakoids.

In spinach thylakoids, the quenching of the singlet excited state in the photosystem II antenna by m-dinitrobenzene does not change the rate of the light induced degradation of the D1 reaction centre protein and offers only limited protection against photoinhibition itself. These results are discussed in terms of the role of non-photochemical quenching as a photoprotective strategy.

CD spectroscopy provides evidence for excitonic interactions involving red-shifted chlorophyll forms in photosystem I.

Selective destruction of the strongly dichroic red-shifted chlorophyll form (C709 nm) in photosystem I (PSI) trimers from Spirulina, by either non-selective high intensity illumination (photobleaching) or incubation with low concentrations of Triton X-100 is accompanied by changes in the circular dichroism spectrum of the same amplitude and of opposite sign at 677 nm. The data are interpreted in terms of a dimeric chlorophyll structure with excitonic bands at these two wavelengths. Similar photobleaching experiments with PSI-200 from maize also suggest the presence of bulk antenna/red form excitonic interactions.