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PURPOSE: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. METHOD: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. RESULTS: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. CONCLUSIONS: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.

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Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.

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This patient, now in her 40s, was evaluated because of genital ambiguity and diagnosed with pAIS in infancy based upon elevated testosterone and gonadotropin levels and significantly reduced binding affinity of the androgen receptor. Such reduced binding is consistent with a structural abnormality of the receptor protein precluding expected activity of the androgen receptor. Based on this information and counseling, her parents chose a female sex assignment. She had clitoral recession and testes removal as an infant and neovaginal surgery using a distal ileum segment at age 11 years and was begun on estrogen therapy at age 12 years. She is being reported now to point out that the data known at her birth provided as specific information to guide sex assignment and genital surgery as is currently available. More importantly, long-term outcome data is very positive showing clear female gender identity, successful marriage of more than 20 years, excellent social relationships including family and friends, an active social life. Since this diagnosis is lifelong, it is inevitable that there will be reminders, hopefully rare, that may be traumatizing. Unfortunately, in this patient, such reminders have been related to access to health care.

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Seabirds interact with fishing vessels to consume fishing discards and baits, sometimes resulting in incidental capture (bycatch) and the death of the bird, which has clear conservation implications. To understand seabird-fishery interactions at large spatiotemporal scales, researchers are increasing their use of simultaneous seabird and fishing vessel tracking. However, vessel tracking data can contain gaps due to technical problems, illicit manipulation, or lack of adoption of tracking monitoring systems. These gaps might lead to underestimating the fishing effort and bycatch rates and jeopardize the effectiveness of marine conservation. We deployed bird-borne radar detector tags capable of recording radar signals from vessels. We placed tags on 88 shearwaters (Calonectris diomedea, Calonectris borealis, and Calonectris edwardsii) that forage in the northwestern Mediterranean Sea and the Canary Current Large Marine Ecosystem. We modeled vessel radar detections registered by the tags in relation to gridded automatic identification system (AIS) vessel tracking data to examine the spatiotemporal dynamics of seabird-vessel interactions and identify unreported fishing activity areas. Our models showed a moderate fit (area under the curve >0.7) to vessel tracking data, indicating a strong association of shearwaters to fishing vessels in major fishing grounds. Although in high-marine-traffic regions, radar detections were also driven by nonfishing vessels. The tags registered the presence of potential unregulated and unreported fishing vessels in West African waters, where merchant shipping is unusual but fishing activity is intense. Overall, bird-borne radar detectors showed areas and periods when the association of seabirds with legal and illegal fishing vessels was high. Bird-borne radar detectors could improve the focus of conservation efforts.

Uso de radares en aves para analizar las interacciones de las pardelas con las pesquerías legales e ilegales Resumen Las aves marinas interactúan con los barcos pesqueros para consumir los cebos y lo que descartan, lo que a veces resulta en la captura accesoria y la muerte del ave, por lo que esto tiene implicaciones claras para la conservación. Los investigadores cada vez usan más el rastreo simultáneo de las aves marinas y los barcos pesqueros para comprender las interacciones aves marinas ­ pesquerías a gran escala espaciotemporal. Sin embargo, los datos del rastreo de barcos pueden incluir vacíos por problemas técnicos, manipulación ilícita o porque no adoptan sistemas para monitorear el rastreo. Estos vacíos pueden llevar a subestimar el esfuerzo de pesca y las tasas de captura accesoria y a comprometer la efectividad de la conservación marina. Desplegamos marcas detectoras de radar encima de aves capaces de registrar las señales de radar de los barcos. Colocamos estas marcas en 88 pardelas (Calonectris diomedea, C. borealis, y C. edwardsii) que forrajean en el noroeste del Mar Mediterráneo y el Gran Ecosistema Marino de Canarias. Modelamos las detecciones del radar de los barcos registradas por las marcas en relación con los datos reticulados de rastreo de barcos del sistema de identificación automático (AIS) para analizar las dinámicas espaciotemporales de las interacciones aves marinas­barcos e identificar áreas con actividad pesquera no reportada. Nuestros modelos mostraron un ajuste moderado (área bajo la curva > 0.7) a los datos de rastreo de barcos, lo que indica una fuerte asociación entre las pardelas y los barcos en los principales sitios de pesca, aunque en las regiones con alto tránsito de barcos las detecciones por radar también fueron causadas por barcos no pesqueros. Las marcas registraron la presencia del potencial de barcos pesqueros sin regular y sin reportar en aguas del oeste de África, en donde los buques mercantes son poco comunes pero la actividad pesquera es intensa. En general, los detectores por radar en las aves mostraron áreas y periodos en donde la asociación entre las aves marinas y los barcos pesqueros legales e ilegales es alta. Estos detectores por radar podrían mejorar el enfoque de los esfuerzos de conservación.

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OBJECTIVES: This meta-analysis aimed to determine the accuracy of currently available computer-assisted implant surgery (CAIS) modalities under in vitro conditions and investigate whether these novel techniques can achieve clinically acceptable accuracy. DATA: In vitro studies comparing the postoperative implant position with the preoperative plan were included. Risk of bias was assessed using the Quality Assessment Tool For In Vitro Studies (QUIN Tool) and a sensitivity analysis was conducted using funnel plots. SOURCES: A systematic search was performed on April 18, 2023, using the following three databases: MEDLINE (via PubMed), EMBASE, and Cochrane Central Register of Controlled Trials. No filters or restrictions were applied during the search. RESULTS: A total of 5,894 studies were included following study selection. Robotic- and static CAIS (sCAIS) had the most accurate and clinically acceptable outcomes. sCAIS was further divided according to the guidance level. Among the sCAIS groups, fully guided implant placement had the greatest accuracy. Augmented reality-based CAIS (AR-based CAIS) had clinically acceptable results for all the outcomes except for apical global deviation. Dynamic CAIS (dCAIS) demonstrated clinically safe results, except for horizontal apical deviation. Freehand implant placement was associated with the greatest number of errors. CONCLUSIONS: Fully guided sCAIS demonstrated the most predictable outcomes, whereas freehand sCAIS demonstrated the lowest accuracy. AR-based and robotic CAIS may be promising alternatives. CLINICAL SIGNIFICANCE: To our knowledge, this is the first meta-analysis to evaluate the accuracy of robotic CAIS and investigate the accuracy of various CAIS modalities.

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OBJECTIVES: To evaluate the accuracy of implant placement using a dynamic navigation system in fully edentulous jaws and to analyze the influence of implant distribution on implant position accuracy. MATERIALS AND METHODS: Edentulous patients who received implant placement using a dynamic navigation system were included. Four to six mini screws were placed in the edentulous jaw under local anesthesia as fiducial markers. Then patients received CBCT scans. Virtual implant positions were designed in the planning software based on CBCT data. Under local anesthesia, implants were inserted under the guidance of the dynamic navigation system. CBCTs were taken following implant placement. The deviation between the actual and planned implant positions was measured by comparing the pre- and postsurgery CBCT. RESULTS: A total of 13 edentulous patients with 13 edentulous maxillae and 7 edentulous mandibles were included, and 108 implants were placed. The average linear deviations at the implant entry point and apex were 1.08 ± 0.52 mm and 1.15 ± 0.60 mm, respectively. The average angular deviation was 2.85 ± 1.20°. No significant difference was detected in linear and angular deviations between the maxillary and mandibular implants, neither between the anterior and posterior implants. CONCLUSIONS: The dynamic navigation system provides high accuracy for implant placement in fully edentulous jaws, while the distribution of the implants showed little impact on implant position accuracy.

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BACKGROUND: The purpose of this in vitro study was to compare the accuracy of implant placement in model surgeries according to the design of the drills (straight drills or step drills) used to finalize the implant bed during pilot-guided static computer-assisted implant surgery (sCAIS). METHODS: Model surgeries were carried out on resin models randomly assigned to three study groups. Virtual planning software (coDiagnostiX 10.6, Dental Wings, Montreal, Canada) was used to plan the implant positions. In Groups 1 and 2, pilot-guided sCAIS was performed. Straight drills were used in Group 1, and step drills were used in Group 2 to finalize the implant beds. In Group 3, fully guided sCAIS was performed using a universal fully guided kit (RealGUIDE Full Surgical Kit 3DIEMME, RealGUIDE, Cantù, Como, Italy). A total of 90 dental implants (Callus Pro, Callus Implant Solutions GmbH, Nuremberg, Germany) were placed (six implants per model, five models per study group). The primary outcome variables (angular deviation, coronal global deviation, and apical global deviation) were calculated for all implants based on the comparison of the preoperative surgical plan with the postoperative scans. RESULTS: Group 2 (coronal global deviation, 0.78 ± 0.29 mm; apical global deviation, 1.02 ± 0.56 mm) showed significantly lower values of both global deviation variables than Group 1 (coronal global deviation, 0.95 ± 0.20 mm; apical global deviation, 1.42 ± 0.49 mm). However, there was no significant difference in angular deviation between Groups 1 and 2 (7.56 ± 2.92° and 6.44 ± 2.84°). Group 3 produced significantly lower values of all three primary outcome variables (angular deviation, 2.36 ± 0.90°; coronal global deviation, 0.59 ± 0.28 mm; apical global deviation, 0.90 ± 0.29 mm) than Group 1 and significantly lower angular deviation and coronal global deviation values than Group 2. CONCLUSIONS: The design of the drills used to finalize implant osteotomies during pilot-guided sCAIS influences dental implant placement accuracy. Using step drills instead of straight drills for final osteotomies decreases deviation from the surgical plan. The fully guided approach performed better than the pilot-guided sCAIS.

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BACKGROUND: The free-access (FA) intravenous alcohol self-administration (IV-ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV-ASA paradigms are associated with self-reported alcohol intake using the timeline follow-back method (TLFB). To evaluate how FA IV-ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B-PEth), and TLFB and measures obtained during IV-ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut-brain peptides involved in AUD pathophysiology. METHODS: Thirty-eight participants completed a laboratory session in which they self-administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV-ASA and subjective alcohol effects were rated during the experiment. RESULTS: The study sample comprised 24 SD and 14 participants with DSM-5 mild AUD. Although BrACs were not associated with B-PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. CONCLUSIONS: No associations between B-PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV-ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV-ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV-ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD.

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OBJECTIVE: To compare implant accuracy of combined static and dynamic (SD) computer-assisted implant surgery (CAIS) with static (S), dynamic (D) CAIS, and freehand surgery (FH) for single implant placement. MATERIALS AND METHODS: One hundred and twenty patients were randomized into four groups. Implants were placed using both stereolithographic surgical guide and dynamic navigation in the SD group, stereolithographic surgical guide in S group, dynamic navigation in D group, and conventional freehand in FH group. Analysis of deviation between planned and final implant position, as well as K means analysis was conducted for implant deviation at platform, apex, and angle (primary outcomes) and directional distribution at platform and apex (secondary outcome). RESULTS: Significant differences were found among the four groups (p < .001): The 3D deviation at the platform (mm) of SD, S, D, and FH groups was 0.62 ± 0.50, 1.06 ± 0.67, 1.02 ± 0.45, and 1.48 ± 0.68, respectively, at apex (mm) was 0.75 ± 0.57, 1.40 ± 0.71, 1.28 ± 0.50, and 2.18 ± 0.95, respectively, and angle (degrees) was 1.24 ± 1.41, 3.18 ± 2.04, 3.28 ± 1.57, and 7.50 ± 4.06, respectively. Deviation at the platform of FH group was significantly more toward mesial (p = .026) and coronal (p = .014) direction, while at the apex, toward distal (p = .004) and lingual (p = .002) than SD group. CONCLUSION: The use of combined static and dynamic CAIS provided significantly higher accuracy than the two alone and freehand surgery for single implant placement.

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OBJECTIVE: Congenital defects of androgen synthesis or action in 46,XY individuals can result in impaired virilisation, despite the apparent testicular development. In a recent case, report of a young adult with complete androgen insensitivity syndrome (CAIS), tumourous gonadal tissue was shown to express HSD17B3 in Sertoli cells (SCs) and not in Leydig cells (LCs). This expression pattern differs from the typical adult human testis and resembles a foetal mouse testis, suggesting an underlying testicular development and function defect. Here, we investigate the effect of altered androgen signalling in gonads from five 46,XY individuals with defects in androgen synthesis or action. METHODS: Gonadal tissue sections from four patients with CAIS, one with CYP17A1 deficiency, and one control were immunostained for LC developmental and steroidogenic markers. The expression of some of these markers during development was investigated by reanalysing previously published single-cell RNA sequencing (scRNA-seq) data from normal human testicular tissues. RESULTS: All gonadal tissues from the patients show an exclusive expression of HSD17B3 in SCs and an expression of the foetal/immature LC marker DLK1 in a subset of LCs, suggesting an androgen-dependent differentiation defect of adult SCs and LCs. Furthermore, reanalysis of scRNA-seq data reveals an expression of HSD17B3 in foetal and neonatal SCs that is downregulated in adult SCs. CONCLUSIONS: Androgen signalling may affect the differentiation of adults, but possibly not foetal SCs or LCs, and may induce a shift of testosterone production from the tubular compartment in the foetal phase to the interstitial compartment in the adult phase.

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OBJECTIVE: To demonstrate the use of a complete digital workflow for a full mouth rehabilitation in a severely worn dentition. CLINICAL CONSIDERATIONS: The present case report successfully rehabilitated a full-mouth case of a severely worn dentition based on the use of digital technologies, making the diagnosis and treatment process faster, accurate and less expensive. A long-lasting esthetic and functional result are showed after 30-months follow up. CONCLUSIONS: An appropriate knowledge on dental erosion and oral rehabilitation, combined with a digital dentistry approach could lead the clinician to deliver a fast, accurate and predictable noninvasive restorative treatment in cases like the one described. CLINICAL SIGNIFICANCE: Bruxism-based severely worn dentition is being found more often in population. In this situation, a detailed diagnosis and tailored treatment are mandatory to obtain a predictable treatment outcome. In this sense, the development of adhesive dentistry, new restorative materials and the incorporation of digital technologies can create a predictable synergy to rehabilitate these types of patients with a modern and less invasive approach.

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Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.

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PURPOSE: In this study, we investigated the vasodilation properties on pre-contracted retinal arteries of a restricted series of carbonic anhydrase inhibitors (CAIs) of the sulfonamide type with enhanced lipophilicity, to assess if it affects the potency of CAIs as vasodilators. METHODS: Carbonic anhydrase (CA) inhibition and in vitro kinetics of the compounds designed and synthesized for testing in this study were assessed by extracting human CA isoform proteins (hCA) from human cells expressing the isoforms of interest, and then measure the affinity of the novel compound for the hCAs by stopped-flow CO2 hydrase spectroscopy. Lipophilicity of compounds was measured by obtaining their octanol-water partition coefficient, expressed as calculated logP. Porcine eyes were obtained from a local abattoir, and the wall tension of porcine retinal arteriole segments dissected from the eyes was measured with small wire vessel myography. The effects of the CA compounds on wall tension were assessed by adding them to the myography bath, after pre-contracting the vessel by prostaglandin analog U-46619. RESULTS: All compounds induced vasodilation but at different concentrations. Among the tested compounds the most potent vasodilators were found to be the seleno-compound 4 and sulfur-ether compound 8 with EC50 values of 7.13 × 10-5 and 7.93 × 10-5 M, respectively, whereas the remaining ones induced complete vasodilation at EC50 comprised within the sub millimolar range. CONCLUSIONS: All the data reported in this study (i.e. results from myography, in vitro kinetics and LogPs) confirm the important role played by several CA isoforms in vasodilation, although the precise mechanism of action still remains to be elucidated.

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AIM: To test four different measurement methods to evaluate deviations between planned and actual implant positions within a digital workflow applying 3D-printed surgical guides. MATERIALS AND METHODS: A fully digital workflow was applied to simulate the single implant insertion to replace a maxillary missing central incisor and first molar in 10 gypsum casts (n = 10). Surgical guides (n = 10 per site) were printed by digital light processing for implant bed preparation and implant insertion. Four methods were used to analyze 3D deviations between the planned (target) and achieved implant positions: Methods 1 and 2 used an automated computer program (ACP) to assess deviations between the initial planning file and a file that represented the actual implant position either by the implant bed [ACP_BED] or by the inserted implant [ACP_IMP]. For Method 3, a standard tessellation language dataset representing the actual implant position was used and equipped with reference planes. This dataset was registered with the target planning, allowing manual measurements [MAN_MEAS]. Method 4 used a reverse engineering approach based on 3D high-resolution scans [REVERSE]. RESULTS: Mean 3D deviations, including for anterior and posterior implant sites, ranged between 0.26 ± 0.11 mm [REVERSE] and 0.40 ± 0.09 mm [ACP_BED] at the implant shoulder, between 0.52 ± 0.24 mm [REVERSE] and 0.91 ± 0.24 mm [ACP_BED] at the implant apex, and between 1.68 and 2.35 degrees in angular deviation. Implant sites did not differ significantly, while some of the evaluation methods differed for shoulder and apex. CONCLUSION: [REVERSE] revealed the smallest deviations between planned and actual implant position. 3D implant deviations were comparable with findings in the literature or even lower.

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We report aryl sulfonamide inhibitors of human carbonic anhydrase (hCA; EC 4.2.1.1) enzymes containing short ureido alkoxy tails. The inhibition potency of such compounds was investigated in vitro on the major hCA isoforms (i.e. I, II, IX, and XII). A selection of the most potent inhibitory derivatives against the hCA IX isoform (i.e. 5a, 5c, and 6c) was studied, and their binding modes on either hCA II and IX-mimic isoform were assessed by X-ray crystallography on the corresponding ligand/protein adducts. This study adds to the field of developing hCA inhibitors at molecular level the critical interactions governing ligand selectivity.

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AIM: The objective of the present case series was to evaluate the 4-year outcomes of implants placed in the esthetic area using static computer-assisted implant surgery (s-CAIS) and restored with a one-abutment one-time (OAOT) protocol using custom-made zirconia abutments and cemented provisional crowns manufactured prior to surgery. Materials and methods: Ten consecutive implants were placed in the esthetic area. Based on a digital implant and prosthodontic planning, surgical guides were ordered and used for the preparation of definitive custom-made zirconia abutments and polymethylmethacrylate provisional crowns. Implants were placed using the s-CAIS guide, and prosthetic components were placed immediately. Implant outcomes were evaluated at the time of surgery, after 4 months, and after 4 years. RESULTS: All implants were successfully placed with s-CAIS and restored with final abutments and provisional crowns. No major prosthetic adverse events were observed. After 4 years, the implant survival rate was 100%, minor peri-implant bleeding on probing was reported, and very stable peri-implant bone levels were observed. The pink esthetic score showed that the prosthetic components were well integrated, and the peri-implant soft tissue was stable. CONCLUSIONS: Within the limitations of the present case series, these results suggest that emerging digital workflows allow the manufacture of final custom-made abutments and provisional crowns prior to surgery. This individualized OAOT procedure may reduce cement-related complications and improve esthetic outcomes by optimizing soft tissue healing with prosthetic components. However, such protocols have evolved toward fully digital workflows, and comparative clinical trials are needed.

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PURPOSE: To study differences in metabolic outcomes between testosterone and estradiol replacement in probands with complete androgen insensitivity syndrome (CAIS). METHODS: In this multicentre, double-blind, randomized crossover trial, 26 women with CAIS were included of whom 17 completed the study. After a two-months run in phase with estradiol, probands either received transdermal estradiol followed by crossover to transdermal testosterone or vice versa. After six months, differences in lipids, fasting glucose, insulin, hematocrit, liver parameters and blood pressure between the treatment phases were investigated. RESULTS: Linear mixed models adjusted for period and sequence did not reveal major group differences according to treatment for the investigated outcomes. In each treatment group, there were however significant uniform changes in BMI and cholesterol. BMI increased significantly, following six months of estradiol ( + 2.7%; p = 0.036) as well as testosterone treatment ( + 2.8%; p = 0.036). There was also a significant increase in total ( + 10.4%; p = 0.001) and LDL-cholesterol ( + 29.2%; p = 0.049) and a decrease in HDL-cholesterol (-15.8%; p < 0.001) following six months of estradiol as well as six months of testosterone treatment (total cholesterol: + 14.6%; p = 0.008; LDL-cholesterol: + 39.1%; p = 0.005, HDL-cholesterol: -15.8%; p = 0.004). Other parameters remained unchanged. CONCLUSION: Transdermal estradiol as well as testosterone treatment in women with CAIS results in worsening in lipid profiles. Given the relatively small sample size, subtle group differences in other metabolic parameters may have remained undetected.

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OBJECTIVES: To compare short-term outcomes after immediate restoration of a single implant in the esthetic zone with one-abutment one-time technique comparing a conventional (control) vs. a fully digital workflow (test). MATERIALS AND METHODS: Eighteen subjects were randomly assigned to the two groups, and a digital implant planning was performed for all. In the test group, a custom-made zirconia abutment and a CAD-CAM provisional crown were prepared prior to surgery; implants were placed using a s-CAIS guide allowing immediate restoration after surgery. In the control group, the implant was placed free-handed using a conventional surgical guide, and a custom-made zirconia abutment to support a stratified provisional crown was placed 10 days thereafter, based on a conventional impression. Implant accuracy (relative to the planning), the provisional restoration outcomes, as well as PROMs were assessed. RESULTS: The implant positioning showed higher accuracy with the s-CAIS surgical guide compared to free-handed surgery (angular deviation (AD): 2.41 ± 1.27° vs. 6.26 ± 3.98°, p < 0.014; entry point deviation (CGD): 0.65 ± 0.37 mm vs. 1.27 ± 0.83 mm, p < 0.059; apical deviation (GAD): 1.36 ± 0.53 mm vs. 2.42 ± 1.02 mm, p < 0.014). The occlusion and interproximal contacts showed similar results for the two workflows (p = 0.7 and p = 0.69, respectively). The PROMs results were similar in both groups except for impression taking with intra-oral scanning preferred over conventional impressions (p = 0.014). CONCLUSIONS: Both workflows allowed implant placement and immediate/early restoration and displayed similar clinical and esthetic outcomes. The fully digital workflow was associated with a more accurate implant position relative to planning. CLINICAL RELEVANCE: Our results show that both conventional and digital workflow are predictive and provide similar clinical outcomes, with extra precision provided by digitalisation.

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OBJECTIVES: This in vitro study aimed to compare the accuracy of implant placement in model surgeries carried out by implementation of three different methods. METHODS: An in vitro study was conducted on 3D printed study models randomly assigned to three study groups. In Group 1, model surgeries were assisted by augmented reality (AR)based dynamic navigation (Innooral System, Innoimplant Ltd, Budapest, Hungary). In Group 2, implants were placed with a free-hand method, and in Group 3, static Computer Assisted Implant Surgery (CAIS) was used (coDiagnostiX software, version 10.4 Dental Wings, Montreal, CA, USA). A total of 48 dental implants (Callus Pro, Callus Implant Solutions GmbH, Hamburg, Germany) were placed (16 implants in four models per study group). The primary outcome variables were angular deviation, coronal, and apical global deviation. These were calculated for all implants based on preoperative registration of the surgical plan and postoperative cone beam computed tomography (CBCT) reconstruction. RESULTS: The accuracy of implant placement using AR-based dynamic navigation showed no significant difference compared to static CAIS (angular deviation, 4.09 ± 2.79° and 3.21 ± 1.52°; coronal deviation, 1.27 ± 0.40 mm and 1.31 ± 0.42 mm; and apical global deviation 1.34 ± 0.41 mm and 1.38 ± 0.41 mm). Global deviation results were significantly lower with AR-based dynamic navigation than with the free-hand approach (coronal and apical global deviation of 1.93 ± 0.79 mm and 2.28 ± 0.74 mm, respectively). CONCLUSIONS: Implant positioning accuracy of AR-based dynamic navigation was comparable to that of static CAIS and superior to that obtained by the free-hand approach. CLINICAL SIGNIFICANCE: Implementing Augmented Reality based dynamic Computer Assisted Implant Surgery (CAIS) in model surgeries may allow to obtain an implant positioning accuracy comparable to that provided by static CAIS, and superior to that obtained through the free-hand approach. Further clinical studies are necessary to determine the feasibility of AR-based dynamic navigation.

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