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Mass spectrometry (MS)-based metabolomics often rely on separation techniques when analyzing complex biological specimens to improve method resolution, metabolome coverage, quantitative performance, and/or unknown identification. However, low sample throughput and complicated data preprocessing procedures remain major barriers to affordable metabolomic studies that are scalable to large populations. Herein, we introduce PeakMeister as a new software tool in the R statistical environment to enable standardized processing of serum metabolomic data acquired by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), a high-throughput separation platform (<4 min/sample) which takes advantage of a serial injection format of 13 samples within a single analytical run. We performed a rigorous validation of PeakMeister by analyzing 47 cationic metabolites consistently measured in 5,000 serum and 420 quality control samples from the Brazilian National Survey on Child Nutrition (ENANI-2019) comprising a total of 224,983 metabolite peaks acquired in 40 days across three batches over an eight-month period. A migration time index using a panel of 11 internal standards was introduced to correct for large variations in migration times, which allowed for reliable peak annotation, peak integration, and sample position assignment for serum metabolites having two flanking internal standards or a single comigrating stable-isotope internal standard. PeakMeister accelerated data preprocessing times by 30-fold compared to manual processing of MSI-CE-MS data by an experienced analyst using vendor software, while also achieving excellent peak annotation fidelity (median accuracy >99.9%), acceptable intermediate precision (median CV = 16.0%), consistent metabolite peak integration (mean bias = −2.1%), and good mutual agreement when quantifying 16 plasma metabolites from NIST SRM-1950 (mean bias = −1.3%). Reference ranges are also reported for 40 serum metabolites in a national nutritional survey of Brazilian children under 5 years of age from the ENANI-2019 study. MSI-CE-MS in conjunction with PeakMeister allows for rapid and automated processing of large-scale metabolomic studies that tolerate nonlinear migration time shifts without complicated dynamic time warping or effective mobility scale transformations.

Background.Stroke is a leading cause of death and disability worldwide and there is a very short period of increased synaptic plasticity, fundamental in motor recovery. Thus, it is crucial to acquire data to guide the rehabilitation treatment. Promising results have been achieved with kinematics and neurophysiological data, but currently, few studies integrate these different modalities. Objectives.We explored the correlations between standardized clinical scales, kinematic data, and EEG measures 4 weeks after stroke. Methods.26 patients were considered. Among them, 20 patients also performed the EEG study, beyond the kinematic analysis, at 4 weeks. Results.We found correlations between the Fugl-Meyer Assessment-Upper Extremity, movement duration, smoothness measures, and velocity peaks. Moreover, EEG measures showed a tendency for the healthy hemisphere to vicariate the affected one in patients characterized by better clinical conditions. Conclusions.These results suggest the relevance of kinematic (in particular movement duration and smoothness) and EEG biomarkers to evaluate post-stroke recovery. We emphasize the importance of integrating clinical data with kinematic and EEG analyses from the early stroke stages, in order to guide rehabilitation strategies to best leverage the short period of increased synaptic plasticity.

Gingival recessions in the mandibular anterior sextant are a common clinical finding, but mucogingival treatment in this location is particularly challenging, due to several anatomical and surgical difficulties. In the present case series, a novel technique, called gingival pedicle with split‐thickness tunnel (GPST), was retrospectively evaluated. Fifteen patients presenting with a single buccal RT1 or RT2 gingival recession of a depth of ≥3 mm in the mandibular anterior sextant were treated by means of the GPST technique. Clinical periodontal parameters at baseline and at the last follow‐up evaluation visit (6–84 months) were compared. Early healing was uneventful in all cases, and no complications such as flap dehiscence or loss of connective tissue graft were observed. Mean root coverage (mRC) was 98.1% ± 7.38%, corresponding to a statistically significant recession reduction (ΔRD) of 4.53 ± 1.19 mm. Complete root coverage was achieved in 14 of 15 cases. The gain in keratinized tissue width amounted to 3.13 ± 0.99 mm and was statistically significant, whereas no significant change in periodontal probing depth was observed after treatment. In conclusion, treatment with GPST technique seems to achieve a favorable and predictable clinical improvement in gingival recessions on mandibular anterior teeth. Why are these cases new information?Limited information is available about the management of isolated deep labial recessions in the mandibular anterior teeth.A novel surgical approach, called GPST technique, is described in a case series to specifically address this type of defect. What are the keys to successful management of these cases?Horizontal incision ≥ RECwidthCut‐back preparation helps to mobilize the flap without tension.CTG width ≥ 3 times RECwidthCTG height ≥ RECdepthProper graft and flap stabilization need to be achieved. What are the primary limitations to success in these cases?Limited mesio‐distal dimensions, which do not allow to obtain a pedicle with adequate horizontal widthVery thin biotype may not be suitable because of the risk of inadequate flap vascularization.

Introduction: Mandibular anterior teeth are most frequently affected by gingival recession. However, data regarding mucogingival treatment aimed at root coverage in this specific location are limited.Objective: The purpose of this study was to systematically review the scientific literature and to use the meta-analytic approach to address the following focused question: “What is the effectiveness of different surgical approaches on clinical and patient-related outcomes in the treatment of buccal gingival recessions on mandibular anterior teeth?”Methods: Studies were located by searching 3 electronic databases (Medline, Scopus, and Cochrane databases) and cross-referencing. Randomized and nonrandomized studies including at least 1 arm involving the use of pedicle flaps and/or free soft tissue grafts in the treatment of gingival recessions (recession type [RT] 1 and RT2) located on the buccal aspects of mandibular centrals, laterals and canines, were included in the analysis. Primary outcome was mean root coverage (mRC), expressed in percentage, based on a 3- to 12-mo follow-up observation. A Bayesian single-arm network meta-analysis was performed to identify a treatment hierarchy of the different surgical techniques.Results: Sixteen studies, with a total of 23 arms, were included in the quantitative analysis. The greatest mRC is associated with laterally positioned flap (LPF) + connective tissue graft (CTG) (91.2%) and tunnel (TUN) + CTG (89.4%), whereas LPF alone, coronally advanced flap (CAF) + CTG, and free gingival graft (FGG) showed lower mRC (79.1%, 78.9%, and 68.5% respectively). TUN + CTG provides significantly greater mRC compared to CAF+CTG. No difference among the procedures could be observed in terms of keratinized tissue width gain.Conclusions: Treatment hierarchy generated by an arm-based network meta-analysis model suggested that tunnel and laterally positioned flap, both in combination with connective tissue graft, may provide the greatest mean root coverage in the treatment of mandibular anterior recessions.Knowledge Transfer Statement: The results of the present systematic review can be used by clinicians when deciding which approach to adopt when treating buccal gingival recessions on mandibular anterior teeth. In particular, procedures based on a laterally positioned flap or a tunneling technique, both in combination with connective tissue graft, seem to be the most predictable therapeutic decision.

Little evidence is available on the loading protocols for implant‐supported overdentures in the treatment of the edentulous maxilla. There are only a few case‐reports available to document the feasibility of immediate loading for maxillary overdenture, and the majority of the publications include the use of splinted implants. This paper presents a case report of immediately loaded narrow diameter implants supporting a maxillary overdenture using Locator abutments. A 64‐year‐old, fully edentulous patient presented with a maxillary complete removable denture. A dual cone beam computed tomography scan was obtained, and the surgical planning was performed. Four 3.3 mm diameter implants were placed at the lateral incisor and second premolar positions, using a guided and flapless approach. Locator abutments were placed, and the denture was connected immediately. The patient was instructed not to remove the prosthesis for 1 week and to follow a soft diet regimen for 2 weeks. Clinical and radiographic evaluation showed positive results at 12 months, with neither prosthetic nor implant complications. This is a proof of principlecase report, which demonstrates the possibility of immediately loading four guided narrow diameter implants supporting a maxillary overdenture using a Locator retention system.

To evaluate the prevalence of Metabolic Syndrome (MetS) and the sensibility and specificity of adiposity indices in relation to MetS diagnosis in postmenopausal Brazilian women.

The allogenic bone ring technique allows for horizontal and vertical bone augmentation with simultaneous implant placement in severely compromised sites. The aim of this report is to present a modified protocol for simultaneous placement of implant and allogenic bone ring graft using a computer‐guided surgery technique. Patient's chief complaint was to replace a missing lateral incisor. The implant site presented both vertical and horizontal tissue deficiencies. Study models and wax‐ups were digitally scanned to stl files and merged with the existing CBCT data in the implant planning software. A 3D representation of an allogenic bone ring was developed, and two digitally designed guides were created: a 5 mm sleeve guide for the implant site and a 7 mm sleeve guide for the allogenic bone ring trephine. Both the implant site and the allogenic bone ring recipient site were prepared using the computer‐generated guides. Once the ring was adapted into the recipient site, the implant was inserted through the allogenic bone ring. The healing was monitored and the implant was restored at 12 months. The accuracy of implant placement was measured and the difference in the final positioning was as follows: 0.6 mm at entry point, 0.55 mm vertical displacement, 1.94 mm at the apex, and angle discrepancy 6.1°. The use of computer‐guided technology for planning and placement of an allograft bone block with simultaneous implant insertion allows for a prosthetically driven team approach to compromised site grafting in addition to improving precision and accuracy when compared with non‐guided techniques.

Gingival recession is a very common mucogingival defect in the adult population, with mandibular central and lateral incisors being the most frequently affected teeth. Limited information is available about the management of isolated deep recession lesions in the mandibular anterior area, where the predictability of the root coverage is reduced by unfavorable anatomical conditions. The purpose of this case report is to present a novel surgical technique for deep labial recessions on mandibular incisors, based on a gingival pedicle with split‐thickness tunneling (GPST), in combination with connective tissue graft (CTG). A 25‐year‐old female patient presented with a Class II Miller isolated buccal recession on #24, 5 × 3 mm. The recipient site design consisted of a laterally positioned flap with a width of 4 mm, in combination with a split‐thickness tunnel preparation that reached the mesial line angle of #25 and extended beyond the mucogingival junction. A CTG (13 × 7 mm) was harvested from the palate and properly adapted over the root surface. Graft and flap were secured with internal mattress and single‐interrupted sutures. Complete root coverage was obtained and maintained at 6 months with excellent esthetic outcomes. This novel surgical approach, based on the combination of laterally displaced pedicle flap and tunneling in addition to CTG, seems to lead to promising results for the treatment of single deep mandibular anterior recessions.

Introduction: Despite recent reports on immediate implant placement in infected sockets, it remains unclear whether positive functional and esthetic results are repeatable in treating teeth with periapical infections. This case report describes important diagnostic factors and decision‐making steps in the treatment planning of a fractured tooth with a periapical lesion in the anterior maxilla. Case Presentation:A healthy, non‐smoking 36‐year‐old male patient presented with the chief complaint of trauma to the right maxillary central incisor. Radiographs displayed horizontal root fracture and a periapical lesion. Treatment comprised extraction of the fractured tooth with minimal trauma, followed by immediate implant placement and provisionalization. Clinical and radiographic analyses at 12 months after surgery showed maintenance of soft‐ and hard‐tissue configuration and symmetry with the contralateral tooth. Conclusions:A multidisciplinary approach and careful case selection are of utmost importance for the successful treatment of challenging implant therapy. This case report shows esthetic and functional results 1 year after the immediate placement and functional loading of an implant in an infected socket in the esthetic zone.

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D‐penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.

This paper describes a surgical techniqueto achieve root coverage in deep, wide gingival recessions using a root isolation procedure with ePTFE membrane, combined with tetracycline conditioning of the root surface and fibrin‐fibronectin sealing system application. The technique was used on 15 patients with isolated mucogingival defects 4 to 6 mm deep. A large trapezium‐shaped flap was raised 3 to 4 mm apical to the margin of the bone dehiscence. The root surface was thoroughly scaled by hand and rotating instruments. Tetracycline HCl solution (100 mg/ml) was topically applied for 4 minutes. Expanded polytetrafluoroethylene (ePTFE) membrane was adapted at least 1 mm coronal to the CEJ and retained in position by sling sutures. A film of fibrin‐fibronectin sealing system was injected between the membrane and the root surface. The flap was sutured coronally and the membrane removed 6 weeks later. The patients were reevaluated 6 months after the reentry procedure. The mean recession depth decreased from 4.7 mm initially to 1.1 mm at the final postoperative appointment. This represents a mean root coverage of 77.4%. Mean probing depth reduction was 0.9 mm and the mean width of keratinized tissue increased from 1.8 mm preoperatively to 2.9 mm 6 months after surgery. These findings show that the treatment of buccal gingival recession using guided tissue regeneration procedure plus tetracycline root demineralization and fibrin‐fibronectin glue application results in a consistent and predictable improvement of mucogingival defects. J Periodontol 1994;65:796–803.

A split‐mouth clinical trialwas designed to evaluate the effect of treating deep wide buccal gingival recession with guided tissue regeneration using expanded polytetrafluoroethylene membrane combined with tetracycline HCl (TTC) root conditioning and fibrin‐fibronecfin sealing system (FFSS) application. Eight patients, aged 25 to 57 years, each presenting two similar mucogingival defects, were selected. The two bilateral recessions were randomly assigned in each patient to either test or control treatment procedure. After initial therapy, each patient was examined for assessment of plaque, gingivitis, recession depth (RD), probing depth (PD), probing attachment level (PAL), and keratinized tissue width (KT). The test procedure included the elevation of mucoperiosteal flap at the buccal aspect of the alveolar process. The root was debrided and demineralized with 100 mg/ml TTC solution for 4 minutes using a burnishing technique with cotton pellets. A teflon membrane was secured and a film of FFSS was applied between the membrane and the root surface. The buccal flap was sutured to completely submerge the membrane. Control treatment included gingival flap surgery with barrier membrane alone. After 6 weeks, the membrane was removed. Healing was evaluated 6 months after surgery. Both test and control procedures resulted in highly significant recession reduction (3.0 mm ± 1.1 and 2.6 mm ± 1.2, respectively) and attachment gain (3.6 mm ± 1.7 and 2.6 mm ± 1.1, respectively). Mean root coverage was of 67% in the TTC+FFSS treated sites and 60% in membrane‐only treated sites. However, only treatment with TTC+FFSS significantly reduced PD and increased KT (P<0.05). When treatments were compared, changes in PD and PAL were significantly greater in TTC + FFSS treated sites (P<0.05). These findings suggest that guided tissue regeneration with barrier membrane is a predictable procedure to treat gingival recession. Clinical results appear to be enhanced by the additional application of fibrin‐fibronectin glue to tetracycline treated roots. J Periodontol 1995; 66:313–320.

Aims and background Fineneedle aspiration cytology (FNAC) is a routine test in the evaluation of breast lesions. We assessed the diagnostic accuracy of mammography (MG), physical examination (PE), ultrasonography (US) and FNAC in 1064 histologically confirmed breast lesions (638 malignant, 426 benign) observed consecutively at the Cancer Prevention Center of Ravenna (Italy).Methods The performance of each test and the additional contribution of FNAC were determined.Results FNAC was done in 69.6 % of cancers and 39.7 % of benign lesions (P = 0.00000), the frequency of aspiration being significantly associated with severity at MG, PE, and US. For FNAC, the true positive rate was 95.1 % and the true negative rate 67.4 %. Only one breast cancer case was detected by FNAC alone (additional true positive rate 0.2 %). The positive predictive value of FNAC in the absence of other abnormalities was 5 %. The negative predictive value of a benign report at MG, PE, US and FNAC was 100 %.Conclusions All breast lesions should be evaluated by all available techniques, especially FNAC, and open biopsy should be avoided for those reported as benign at all tests.

Aims In 1990, The Bethesda System (TBS) was introduced into spontaneous cervical screening practice in Ravenna, Italy. Negative/benign reports with the recommendation for early repeat smears (RERS) due to some limitation in sample adequacy were considered no longer acceptable. A monitoring program for the rate of unsatisfactory smears (UNS) was implemented. The aim of the present study was to evaluate the effects of such changes in the screening procedure.Methods The frequency of UNS in 1990 was compared with that of UNS+RERS in 1988 (assumed as a baseline year) by the calculation of the standardized rate ratio with the 95% confidence interval (CI). The trend in the standardized rate of UNS from 1990 to 1994 was evaluated by the calculation of the average annual variation with the 95% CI.Results The immediate effect of TBS (1990:1988 comparison) was a significant increase in the rate of UNS attributable to scant cellularity, poor fixation and thick areas (rate ratio, 2.35; 95% CI, 2.18 to 2.53) and to the absence of endocervical component (1.45; 95% CI, 1.30 to 1.60). The rate of UNS attributable to the presence of cytolysis, inflammation, blood and foreign material decreased by about 6 times (0.16; 95% CI, 0.13 to 0.19). The midterm effect of TBS (trend from 1990 to 1994) was a decrease in the total rate of UNS by an average of 2.3% per year. The downward trend was significant for smears showing scant cellularity, poor fixation and thick areas (-1.5% per year) and the absence of endocervical component (-0.7% per year). UNS attributable to the presence of cytolysis, inflammation, blood and foreign material stabilized.Conclusions TBS led to a substantial change in the type of information provided by the cytology report (Immediate effect). The monitoring program according to TBS led to a reduction in UNS attributable to sample taker (midterm effect).

In Italy, where no national screening program for cervical cancer exists, organized programs have developed on a local basis. We performed the first survey of existing organized programs by mailing a standard questionnaire to a large network of possibly involved services. For the present survey, a program was defined as organized if personal invitations were sent. We identified 29 already active organized programs and 4 others in a starting phase. The target population of active programs included 2,074,820 women in the age range 25-64 years, corresponding to 13.5% of the Italian female population of the same age. The situation is rapidly evolving since many regional programs are being implemented. Most programs followed Italian and European recommendations as regards the age limits, interval between screening rounds, presence of a fail-safe system for women referred for colposcopy, presence of protocols for diagnostic workup and treatment, and presence of referral centers for such phases. However, many programs did not meet national guidelines as regards the size of laboratories interpreting smears, which were frequently small. Second-level referral centers also frequently had a very small activity. The average (weighted for size of the invited population) compliance to invitation and coverage (proportion of women with at least one test in the last 3 years) was 32.6% and 66.0%, respectively, therefore needing to be improved. Compliance to colposcopy (weighted for number of referred women) was 81.4%. We found a very high variability in the proportion of women referred for colposcopy that could only be partly explained by different referral protocols and could depend on different criteria of smear interpretation: the average (weighted for number of tested women) was 2.01%. A need for improvement in the process of evaluation and for homogenization of criteria of cytology interpretation was identified: work in this regard is ongoing.

Twenty‐four(24) deep wide buccal gingivalrecessions were treated with ePTFE membrane according to guided tissue regeneration principles (GTR). Factors affecting the surgical outcome of the regenerative procedure were retrospectively analyzed. In 16 cases, the barrier membrane was used in conjunction with tetracycline root conditioning and fibrin‐fibronectin system application, and 8 cases were treated with the membrane alone. Healing response was evaluated 12 months after surgery. Since no difference was observed between the two treatment protocols, all available data were grouped. Mean recession depth was reduced from 4.6 mm to 1.3 mm postoperatively, which represents an average root coverage of 71.7%. Fifty percent (50%) of the cases showed clinical attachment gain greater than or equal to 4 mm and a mean increase of keratinized tissue of 1.0 mm was observed. Baseline recession depth and extent of membrane exposure at the reentry procedure significantly influenced the amount of newly‐formed tissue under the membrane. Recession reduction positively correlated with the preoperative recession depth and the regenerated tissue gain. Treatment was also affected by tooth location, recession reduction, and attachment gain, being significantly greater in upper than lower archs. Results suggest that GTR technique represents a predictable procedure to improve the soft tissue conditions of deep mucogingival defects. Randomized controlled trials of other forms of management of mucogingival defects as compared to the GTR technique will be necessary to fully evaluate the utility of the GTR technique. J Periodontol 1995; 66:14–22.

Human papillomavirus cervical infection was investigated in a series of 300 unselected women by comparing morphological diagnoses (cytology and histology) with results of DNA hybridization techniques (filter in situ hybridization of DNA from exfoliated cervical cells and Southern blot analysis of HPV-DNA in cervical biopsy specimens). The prevalence of HPV cervical infection diagnosed by PAP smears was 11.6 %.Despite disadvantages, filter in situ hybridization was confirmed to be particularly useful for screening purposes to detect HPV in cervical scrapings. In 3 cases it was the only applicable method for diagnosing « high-risk » HPV infection. Southern blot hybridization of tissue DNA with HPV 16-DNA revealed the presence of this virus in 8 cases, and HPV 31-DNA and HPV 42-DNA in 1 case each.

The authors report on a consecutive retrospective series of 150 male breast cancers. Clinical, diagnostic and therapeutic features are compared over time and with respect to a large consecutive series of female breast cancers. Both age at diagnosis and tumor stage were more advanced in males than in females. Poor alertness of both men and doctors for this unfrequent disease may account for such a delay in diagnosis. The use of mammography increased over time and sonography or cytology were frequently and successfully employed in the last decade. Unfortunately no improvement of tumor stage at diagnosis was observed over time in the present series. A time trend was also evident for the type of surgical and postoperative treatment. Modified radical mastectomy and adjuvant chemo- or hormone therapy were increasingly adopted, although Halsted operation and postoperative radiotherapy were still common in the last decade due to the relatively high proportion of locally advanced T3-4 cancers. Both disease-free and overall survival were worse in men than in women, even after adjustment by stage at diagnosis. This study suggests that male breast cancer has a worse prognosis with respect to female breast cancer and provides no complete explanation of this finding, except for an intrinsic higher aggressivity. No evidence was found which may justify a different diagnostic or therapeutic approach with respect to female breast cancer.

Aims and background The prognosis for ovarian cancer patients depends on the stage at diagnosis. As a prerequisite for any proposed procedure for ovarian cancer screening, high levels of specificity should be obtained using combinations of tests. Based on preliminary data from an ongoing feasibility study, this report is focused on the possible gain in specificity provided by fine-needle aspiration of occult ovarian masses detected by ultrasound.Methods Ultrasonography was used as a basic test, and fine-needle aspiration was obtained from selected patients. Those with (a) positive aspiration cytology or histology, (b) complex or solid masses showing volume increase, (c) complex or irregular masses and inadequate samples, and (d) recurrent cystic lesions were operated on.Results A total of 3541 asymptomatic patients 50-69 years of age underwent ultrasonography, and 98 were selected for fine-needle aspiration. Of these, 19 (positivity rate 19/3541 or 0.5%) were operated on. Two ovarian cancer cases (FIGO Stage II and III) were detected (detection rate 2/3541 or 0.6 × 1,000; positive predictive value 2/19 or 10.5%). Specificity was 3443/3539 or 97.3% for ultrasound alone and 3522/3539 or 99.5% for the procedure as a whole. Surgical exploration for relapses of benign cysts reduced by some 50% the potential gain in positive predictive value provided by aspiration cytology compared with ultrasound alone.Conclusions Although fine-needle aspiration has improved the performance of ultrasound, this 2-levei procedure does not appear to achieve acceptable levels of specificity.

Aims and Background In the field of breast cancer control, obtaining population-based data on spontaneous mammography (MG) screening should be a priority. This study focuses on the breast cancer incidence and stage distribution in relation to MG use in Ravenna (Italy), 1987-88.Methods We estimated the MG rates, expected (E) incidence based on mortality data, observed (O) incidence, predicted excess incidence based on MG rates, observed excess incidence, and stage distribution according to the MG history.Results The highest MG rate (37%) was found among residents aged 40-44 but none of these had a T1a-bN0 breast cancer diagnosed nor was the predicted excess incidence demonstrated. Between 45 and 64 years, 80% of self-selected screenees had repeat (“incidence”) MG and the O:E incidence ratio was 1.32 (95% Cl 1.09-1.58). The observed excess incidence was 3.8-fold (95% Cl 2.56-5.16) greater than that predicted. Advanced (T2+ and/or N1+) cases accounted for 42% of patients diagnosed within 3 years of their last MG, for 55% of those diagnosed more than 3 years after their last MG, and for 70% of those with no previous MG. Above age 70, a significant worsening of stage at diagnosis was associated with a clear-cut drop in the proportion of breast cancer patients with previous self-referral for MG.Conclusions The results indicate that self-selection and its implications are major features of spontaneous screening practice.