Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.

A spatiotemporal proteomic map of human adipogenesis.

White adipocytes function as major energy reservoirs in humans by storing substantial amounts of triglycerides, and their dysfunction is associated with metabolic disorders; however, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generate a spatiotemporal proteomic atlas of human adipogenesis, which elucidates cellular remodelling as well as the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and highlights the coordinated regulation of protein localization and abundance during adipocyte formation. We identify compartment-specific regulation of protein levels and localization changes of metabolic enzymes to reprogramme branched-chain amino acids and one-carbon metabolism to provide building blocks and reduction equivalents. Additionally, we identify C19orf12 as a differentiation-induced adipocyte lipid droplet protein that interacts with the translocase of the outer membrane complex of lipid droplet-associated mitochondria and regulates adipocyte lipid storage by determining the capacity of mitochondria to metabolize fatty acids. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Scientific rationale for study: Consistent data on the outcomes of treatments for full-arch edentulism are fundamental for establishing high-quality clinical practices with effective impact on patients' lives. Principal findings: Despite the increasing number of studies assessing the rehabilitation of full-arch edentulism with implant-supported prostheses, there has been little adherence to reporting guidelines (EQUATOR network), resulting in high variability regarding the type of outcomes reported. The clinical performance of these restorations has been mostly evaluated using clinician-oriented and patient-reported outcomes. Assessment methods are frequently not described and vary across studies. Practical implications: It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

Rehabilitation of full-arch edentulism with fixed or removable dentures retained by root-form dental implants: A systematic review of outcomes and outcome measures used in clinical research in the last 10 years.

AIM: To evaluate outcome measures, methods of assessment, and analysis in clinical studies on the rehabilitation of full-arch edentulism with implant-supported fixed or removable prostheses. MATERIALS AND METHODS: A protocol-oriented search was conducted in MEDLINE via PubMed, EMBASE, and Cochrane Library (PROSPERO registration CRD42021265179) from 1 January 2011 to 27 July 2021 to identify longitudinal studies reporting on the rehabilitation of edentulous patients with implant-supported prostheses. The primary aim of this study was the collection of all objectively reported outcomes in each study. Secondary aims included the description of the methods of assessment and analytical methods. Risk of bias was applied according to the study design (randomized controlled trial, cohort study, or descriptive pre-post study). Individual study data were extracted into an outcomes matrix. Outcomes were grouped into domains and descriptively analysed. A network diagram was generated to establish relationships between domains. The present review follows the PRISMA statement. RESULTS: The screening and selection processes resulted in the identification of 491 publications, corresponding to 421 different studies (cohorts of patients). Only 24% of the studies reported the use of EQUATOR network guidelines. Implant failure/survival was the most reported outcome (270 studies), but the criterion to determine implant failure and/or survival was frequently not described or was ambiguous. Implant success was much less frequently reported (88) and was based on several heterogenous composite definitions. Marginal bone levels (233 studies), technical complications (158), and clinical outcomes (150), including peri-implant soft tissue and implant stability assessment, were also frequently reported. Patient-reported outcome measures (PROMs) (145) and function-based outcomes (40) were predominantly reported in isolation from other outcomes and most frequently in removable restorations. While quality of life was evaluated using valid instruments, patient satisfaction was evaluated based on a common sense concept of satisfaction. Economic outcomes were under-reported (13). CONCLUSIONS: There is great heterogeneity in the criteria to define implant failure or survival and implant success, which prevents the comparison of rates across studies. Even though studies frequently report multiple outcomes, PROMs are usually reported in isolation from other outcomes. It would be valuable to have a set of core outcome variables and standardized methods of measurement for future studies.

DNA damage independent inhibition of NF-κB transcription by anthracyclines.

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes in primary mouse (Mus musculus) macrophages. Using an NMR-based structural approach, we demonstrate that anthracyclines disturb the complexes formed between the NF-κB subunit RelA and its DNA-binding sites. The anthracycline variants Aclarubicin, Doxorubicinone, and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other anthracyclines but do not induce DNA damage, also suppressed inflammation, thus uncoupling DNA damage from the effects on inflammation. These findings have implications for anticancer therapy and for the development of novel anti-inflammatory drugs with limited side effects for life-threatening conditions such as sepsis.

The burden of coronary heart disease in simultaneous pancreas-kidney transplantation: coronary angiography as a diagnostic method for all? - a retrospective study / O peso da doença arterial coronariana no transplante de pâncreas-rim simultâneo: angiografia coronária como método diagnóstico para todos? - um estudo retrospectivo

Abstract Introduction: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. Methods: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. Results: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. Discussion: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Resumo Introdução: O diabetes mellitus tipo 1 está associado ao risco aumentado de doença arterial coronariana, que é frequentemente assintomática. Este risco aumenta significativamente em pessoas com nefropatia. Em pacientes selecionados, o transplante de pâncreas- rim simultâneo é a terapia substitutiva, renal e pancreática, de escolha, pois aumenta a longevidade e estabiliza complicações diabéticas. Apesar de essenciais, protocolos de triagem universais ainda são controversos para doença arterial coronariana nesta população. Métodos: Analisamos retrospectivamente 99 receptores de pâncreas-rim simultâneo de nosso centro, de 2011 a 2018, e selecionamos 77 pacientes que realizaram angiografia coronária durante avaliação pré-transplante. Nosso objetivo foi identificar fatores de risco potenciais associados a lesões significativas na angiografia coronária. Resultados: Quase metade de nossa coorte de 77 candidatos submetidos à angiografia coronária apresentou doença arterial coronariana. Destes, quase 30% foram submetidos à revascularização, embora apenas um tenha relatado sintomas de isquemia miocárdica. Em uma análise univariada, a presença do hábito de fumar foi o único fator de risco para doença arterial coronariana. Também descobrimos que 20 ou mais anos de diabetes mellitus tipo 1 estavam significativamente associados à presença de coronariopatia. Discussão: A seleção de candidatos diabéticos com risco cardíaco aceitável antes do transplante de pâncreas-rim simultâneo é imperativa. Dado o impacto de um diagnóstico correto e baixo risco de procedimento, defendemos o uso rotineiro da angiografia coronária como método de triagem inicial para doença arterial coronariana nesta população. Deve-se ter um cuidado especial na avaliação de pacientes assintomáticos com diabetes mellitus tipo 1 de longa duração e fumantes.

The burden of coronary heart disease in simultaneous pancreas-kidney transplantation: coronary angiography as a diagnostic method for all? - a retrospective study.

INTRODUCTION: Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. METHODS: We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. RESULTS: Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. DISCUSSION: Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Management of Pulp Canal Obliteration-Systematic Review of Case Reports.

Background and Objectives: This systematic review aimed to assess the literature focusing on the clinical management of traumatized teeth with Pulp Canal Obliteration (PCO) and propose an updated clinical decision-making algorithm. The present review follows the PRISMA guidelines and was registered on PROSPERO database (CRD42020200656). Materials and Methods: An electronic search strategy was performed in Pubmed, EBSCOhost and LILACS from inception to March 2021. Only anterior permanent teeth with PCO due to dental trauma were included. Regarding clinical approaches, only teeth managed with a "watchful waiting" approach, tooth bleaching or root canal treatment (RCT) were included. Quality assessment was performed using the JBI Critical Appraisal Tool for Case Reports. Results: Twenty case reports were selected, resulting in a total of 27 patients. The number of traumatized teeth diagnosed with PCO was 33. The "watchful waiting" approach was the most implemented clinical strategy. Discolored non-symptomatic PCO teeth were mostly managed with external bleaching. The prevalence of pulp necrosis (PN) was 36.4%. For teeth diagnosed with PN, non-surgical RCT was performed in 10 teeth and surgical RCT in one tooth. Guided endodontic technique was performed in six of those teeth. Conclusions: For discolored non-symptomatic PCO teeth, external bleaching is advocated and the RCT approach should not be implemented as a preventive intervention strategy. Symptomatic PCO teeth should follow regular endodontic treatment pathways. Clinical approach of teeth with PCO should follow a decision-making algorithm incorporating clinical and radiographic signs and patient-reported symptoms.

Impact of the COVID-19 pandemic on breast and cervical cancer stage at diagnosis in Brazil.

BACKGROUND: The COVID-19 pandemic has led to the need for health services adjustments, which may have compromised management of other diseases. For cancer patients, delays may significantly impair outcomes in some situations. We aimed to assess the impact of the COVID-19 pandemic in breast and cervical cancer diagnosis and treatment compared to the same period prior to the pandemic. METHODS: Data were collected from patients attending their first visit to a Brazilian cancer centre from 1 September 2020 to 31 January 2021 and from 1 September 2019 to 31 January 2020. The pandemic started in February 2020 in Brazil and is still ongoing. We considered this period (September/20-January/21) to be representative of the pandemic impact on cancer management. The primary endpoint was breast and cervical cancer stages at diagnosis. RESULTS: A total of 268 breast cancer patients and 44 cervical cancer patients had their first consult in our cancer centre from September/20 to January/21; 457 and 60, respectively, occurred from September/19 to January/20. Patients who attended their first visit during the pandemic (September/20-January/21) presented with more advanced-stage breast cancer (p < 0.001) and cervical cancer (p = 0.328) than those in the period prior to the pandemic (September/19-January/20), although the difference was not statistically significant for cervical cancer. The proportion of cervical cancer patients diagnosed with locally advanced disease (stages III-IVA) was 56.8% (N = 25) in September/20-January/21 compared to 43.3% (N = 26) in September/19-January/20. Similarly, 37.3% (N = 100) of breast cancer patients had stage III disease in September/20-January/21 compared to 23.2% (N = 106) in September/19-January/20. Fewer breast cancer patients (13.7%) were diagnosed due to screening tests during the pandemic than before it (25.5%) (p < 0.001). CONCLUSIONS: Breast and cervical cancer patients had more advanced-stage diseases in their first visit to a cancer centre during the COVID-19 pandemic compared to a similar period prior to the pandemic. Efforts should be made not to compromise essential cancer services since this results in long-term negative impacts for oncologic patients.

Influence of Preoperative Pulp Inflammation in the Outcome of Full Pulpotomy Using a Dog Model.

INTRODUCTION: This study aimed to evaluate the impact of preoperative pulp inflammation on the histologic outcome of full pulpotomy performed in mature permanent posterior teeth using 4 different biomaterials. METHODS: Five beagle dogs (providing a total of 120 roots) were selected. Dentin exposure was performed in teeth from the second and third quadrants. One week later, full pulpotomy procedures were performed using 4 different bioactive materials (ProRoot MTA [MTA], TotalFill BC Putty [BC], Biodentine [BIO], and an experimental cement [ie, pulp capping material]). The hemostasis time was registered. After 14 weeks, the animals were killed. Pulp-dentin tissues were histologically and radiographically assessed. The significance level was set at .05. RESULTS: Teeth with previously exposed dentin revealed a statistically significant increase in the time required to achieve hemostasis (P < .001), therefore confirming the pulp inflammation status induced by 1-week exposure of occlusal dentin before performing full pulpotomy. There was no radiographic evidence of root resorption, periapical radiolucency, or lamina dura alterations. No statistically significant differences were observed between normal and inflamed pulp regardless of the evaluated histologic parameters. Moreover, histologic data concerning calcified barrier formation and the pulp tissue response show better results for BIO without statistical differences compared with MTA or BC (P > .05). The pulp capping material presented a lower performance, with statistically significant differences being detected in regard to the remaining 3 tested materials (P < .001). CONCLUSIONS: Radiographic and histologic outcomes of full pulpotomy are not jeopardized by short-term preoperative pulp inflammation. Moreover, BIO, MTA, and BC cements present suitable alternatives to be used as pulp capping agents.

Clinical and radiographic performance of self-locking conical connection implants in the posterior mandible: Five-year results of a two-centre prospective study.

OBJECTIVE: This prospective study aims to assess the 5-year clinical performance of implants with internal conical connection and platform-switched abutments in the posterior mandible. MATERIAL AND METHODS: Healthy adults missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent implants. After a transmucosal healing period single crown restorations were cemented on platform-switched abutments. Changes in marginal bone levels were investigated in standardized periapical radiographs from surgery and loading (baseline) to 60-months post-loading. RESULTS: Twenty-four patients received 52 implants. Bone remodelling took place between surgery and loading (mean:-0.5, SD:±0.4 mm). From loading to 60 months, there was a mean bone change of 0.27 (SD:±0.47 mm) which stabilized 24 months after prosthesis delivery (mean:0.2, SD:±0.46 mm). 71.7% of all implants presented bone preservation at 60 months irrespective of the initial insertion depth. Two implants were lost after 5 years and the success rate was 95.1%. Patient enquiry revealed high satisfaction. CONCLUSION: Internal conical connection implants with platform-switched abutments presented a high success rate and preservation of marginal bone levels at the implant shoulder after 5 years of loading.

Latent leprosy infection identified by dual RLEP and anti-PGL-I positivity: Implications for new control strategies.

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.

Recommendations for Implant-Supported Full-Arch Rehabilitations in Edentulous Patients: The Oral Reconstruction Foundation Consensus Report.

The tasks of Working Groups 1 to 6 at the 4th Consensus Meeting of the Oral Reconstruction Foundation were to elucidate clinical recommendations for implant-supported full-arch rehabilitations in edentulous patients. Six systematic/narrative reviews were prepared to address the following subtopics: (1) the influence of medical and geriatric factors on implant survival; (2) the prevalence of peri-implant diseases; (3) the influence of material selection, attachment type, interarch space, and opposing dentition; (4) different interventions for rehabilitation of the edentulous maxilla; (5) different interventions for rehabilitation of the edentulous mandible; and (6) treatment choice and decision-making in elderly patients. Consensus statements, clinical recommendations, and implications for future research were determined based on structured group discussions and plenary session approval.

Different Interventions for Rehabilitation of the Edentulous Maxilla with Implant-Supported Prostheses: An Overview of Systematic Reviews.

PURPOSE: To synthesize evidence derived from systematic reviews (SRs) on different interventions for rehabilitation of the edentulous maxilla with implant-supported restorations. MATERIALS AND METHODS: A protocol-oriented search was established to address the PICO question: What is the current evidence regarding rehabilitation of the edentulous maxilla with different implant-supported prostheses in terms of implant and prosthesis survival? The primary outcomes were implant and prosthesis survival rates evaluated from SRs of clinical studies including adult patients with complete edentulism of the maxilla and comparing different implant-supported rehabilitation strategies. Methodologic quality of the SRs was assessed with the AMSTAR-2 tool. RESULTS: The final selection process led to the inclusion of 36 SRs that were grouped as: (1) addressing maxillae with sufficient bone to place implants; (2) addressing maxillae with insufficient bone to place implants; and (3) comparing different types of prosthesis, number of implants, patient-reported outcomes, and economic evaluations. The literature describes four or more implants as suitable for full-arch fixed prostheses and implant-supported overdentures; in both cases, the overall survival rate is > 95%. Mini-implants present very high short-term failure rates (> 30%). Poor description of technical complications, adjustments, and maintenance and corresponding costs precluded a cost-effectiveness analysis. CONCLUSION: No implant-supported rehabilitation of the edentulous maxilla (fixed or removable) should be supported on fewer than four implants. A one-piece full-arch fixed dental prosthesis can be supported by a minimum of two anterior axial plus two posterior distally tilted implants or by six to eight axial implants symmetrically distributed through the posterior and anterior regions of the arch. Four to six implants is the advised number to support an overdenture. The use of mini-implants in the maxilla is inadvisable.

Different retinopathy phenotypes in type 2 diabetes predict retinopathy progression.

PURPOSE: To characterize the progression in retinopathy severity of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes. DESIGN AND METHODS: Patients with type 2 diabetes and mild NPDR (ETDRS 20 or 35) were followed in a 5-year longitudinal study. Examinations, including color fundus photography (CFP) and optical coherence tomography (OCT and OCTA), were performed at baseline, 6 months and then annually. Phenotype classification was performed based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Phenotype A is characterized by low MAT (< 6) and normal CRT; Phenotype B by low MAT (< 6) and increased CRT; and Phenotype C by higher MAT (≥ 6) with or without increased CRT. ETDRS grading of seven fields CFP was performed at the initial and last visits. RESULTS: Analysis of ETDRS grade step changes showed significant differences in diabetic retinopathy (DR) progression between the different phenotypes (p < 0.001). Of the 66 participants with phenotype A only 2 eyes (3%) presented 2-or-more-step worsening. None of the 50 participants characterized as phenotype B developed 2-step worsening, whereas 13 eyes (23.2%) characterized as phenotype C had 2-or-more-steps worsening. Phenotype C presents the higher risk for 2-or-more step worsening (OR: 15.94 95% CI: 3.45-73.71; p < 0.001) and higher sensitivity, correctly identifying 86.7% of cases at risk (AUC: 0.84 95% CI: 0.72-0.96; p < 0.001). Diabetic retinopathy severity progression was associated with HbA1c (p = 0.019), LDL levels (p = 0.043), and ocular factors as MAT (p = 0.010), MA formation rate (p = 0.014) and MA disappearance rate (p = 0.005). Capillary closure at 5-year follow-up, identified by lower vessel density (VD) on OCTA, was also associated with diabetic DR severity progression (p = 0.035). CONCLUSIONS: Different DR phenotypes in type 2 diabetes show different risks of retinopathy progression. Phenotype C is associated with increased HbA1c values and presents a higher risk of a 2-or-more-step worsening of the ETDRS severity score.

The dynamics of linear polyubiquitin.

Polyubiquitin chains are flexible multidomain proteins, whose conformational dynamics enable them to regulate multiple biological pathways. Their dynamic is determined by the linkage between ubiquitins and by the number of ubiquitin units. Characterizing polyubiquitin behavior as a function of their length is hampered because of increasing system size and conformational variability. Here, we introduce a new approach to efficiently integrating small-angle x-ray scattering with simulations allowing us to accurately characterize the dynamics of linear di-, tri-, and tetraubiquitin in the free state as well as of diubiquitin in complex with NEMO, a central regulator in the NF-κB pathway. Our results show that the behavior of the diubiquitin subunits is independent of the presence of additional ubiquitin modules and that the dynamics of polyubiquitins with different lengths follow a simple model. Together with experimental data from multiple biophysical techniques, we then rationalize the 2:1 NEMO:polyubiquitin binding.

Present Status in Polymeric Mouthguards. A Future Area for Additive Manufacturing?

Athletes from contact sports are more prone to orofacial injuries because of the exposure to possible shocks and collisions derived from physical proximity. The use of protector polymeric mouthguards proved to be useful in the prevention of the described injuries. There are different types of mouthguards with varying ranges of protection and prices, but they are all made from polymers and share the same propose: to absorb and dissipate the impact energy resulting from the shocks. As they are used inside the mouth, they should not impair breathing and speaking nor compromise the comfort of the athlete. However, the ideal mouthguard is yet to be created. The choice of the most appropriate polymeric material and the standard required properties have not yet been reported. Regardless of the numerous studies in this field, normalized control parameters for both material characterization and mouthguard fabrication are absent. This paper aims to present a review of the current types of available mouthguards and their properties/characteristics. Moreover, a detailed description of the most common polymers for the fabrication of mouthguards, together with the manufacturing techniques, are discussed.

Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy.

Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular edema (DME) and proliferative retinopathy (PDR). To test these findings, 212 persons with type 2 diabetes (T2D) and mild nonproliferative retinopathy (NPDR), one eye per person, were followed for five years with annual visits. Of these, 172 completed the follow-up or developed an outcome: PDR or DME (considering both clinically significant macular edema (CSME) and center-involved macular edema (CIME)). Twenty-seven eyes (16%) developed either CSME (14), CIME (10), or PDR (4), with one eye developing both CSME and PDR. Phenotype A showed no association with development of vision-threatening complications. Seven eyes with phenotype B and three with phenotype C developed CIME. Phenotype C showed higher risk for CSME development, with 17.41 odds ratio (p = 0.010), compared with phenotypes A + B. All eyes that developed PDR were classified as phenotype C. Levels of HbA1c and triglycerides were increased in phenotype C (p < 0.001 and p = 0.018, respectively). In conclusion, phenotype C identifies eyes at higher risk for development of CSME and PDR, whereas phenotype A identifies eyes at very low risk for vision-threatening complications.