The Efficacy of a New AMCOP® Elastodontic Protocol for Orthodontic Interceptive Treatment: A Case Series and Literature Overview

Background: Elastodontics is a specific interceptive orthodontic treatment that uses removable elastomeric appliances. They are functional appliances that produce neuromuscular, orthopedic and dental effects. Thus, these devices are useful in the developmental age, when skeletal structures are characterized by important plasticity and adaptation capacity, allowing to remove factors responsible for malocclusions. Elastomeric devices are generally well tolerated by patients requiring simple collaboration and management. This work can be useful to update all orthodontists already adopting these appliances or for those who want to approach them for the first time. This study aimed to describe four cases treated with new elastomeric devices called AMCOP Bio-Activators and to provide an overview of elastodontics, its evolution, indications and limits. Methods: A total of four clinical cases were presented after a treatment period of 16–20 months to evaluate the clinical and radiological effects of the elastodontic therapy. Results: The effectiveness of Bio-Activators on clinical cases was evidenced with a significant improvement in skeletal and dentoalveolar relationship, and malocclusion correction in a limited treatment period (16–20 months). Conclusions: The Bio-Activators showed clinical effectiveness to achieve therapeutic targets according to a low impact on the patient’s compliance.

The effect of casein glycomacropeptide versus free synthetic amino acids for early treatment of phenylketonuria in a mice model

Introduction Management of phenylketonuria (PKU) is mainly achieved through dietary control with limited intake of phenylalanine (Phe) from food, supplemented with low protein (LP) food and a mixture of free synthetic (FS) amino acids (AA) (FSAA). Casein glycomacropeptide (CGMP) is a natural peptide released in whey during cheese making by the action of the enzyme chymosin. Because CGMP in its pure form does not contain Phe, it is nutritionally suitable as a supplement in the diet for PKU when enriched with specific AAs. Lacprodan® CGMP-20 (= CGMP) used in this study contained only trace amounts of Phe due to minor presence of other proteins/peptides. Objective The aims were to address the following questions in a classical PKU mouse model: Study 1, off diet: Can pure CGMP or CGMP supplemented with Large Neutral Amino Acids (LNAA) as a supplement to normal diet significantly lower the content of Phe in the brain compared to a control group on normal diet, and does supplementation of selected LNAA results in significant lower brain Phe level?. Study 2, on diet: Does a combination of CGMP, essential (non-Phe) EAAs and LP diet, provide similar plasma and brain Phe levels, growth and behavioral skills as a formula which alone consist of FSAA, with a similar composition?. Material and methods 45 female mice homozygous for the Pahenu2 mutation were treated for 12 weeks in five different groups; G1(N-CGMP), fed on Normal (N) casein diet (75%) in combination with CGMP (25%); G2 (N-CGMP-LNAA), fed on Normal (N) casein diet (75%) in combination with CGMP (19,7%) and selected LNAA (5,3% Leu, Tyr and Trp); G3 (N), fed on normal casein diet (100%); G4 (CGMP-EAA-LP), fed on CGMP (70,4%) in combination with essential AA (19,6%) and LP diet; G5 (FSAA-LP), fed on FSAA (100%) and LP diet. The following parameters were measured during the treatment period: Plasma AA profiles including Phe and Tyr, growth, food and water intake and number of teeth cut. At the end of the treatment period, a body scan (fat and lean body mass) and a behavioral test (Barnes Maze) were performed. Finally, the brains were examined for content of Phe, Tyr, Trp, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA), and the bone density and bone mineral content were determined by dual-energy x-ray absorptiometry. Results Study 1: Mice off diet supplemented with CGMP (G1 (N-CGMP)) or supplemented with CGMP in combination with LNAA (G2 (N-CGMP-LNAA)) had significantly lower Phe in plasma and in the brain compared to mice fed only casein (G3 (N)). Extra LNAA (Tyr, Trp and Leu) to CGMP did not have any significant impact on Phe levels in the plasma and brain, but an increase in serotonin was measured in the brain of G2 mice compared to G1. Study 2: PKU mice fed with mixture of CGMP and EAA as supplement to LP diet (G4 (CGMP-EAA-LP)) demonstrated lower plasma-Phe levels but similar brain- Phe levels and growth as mice fed on an almost identical combination of FSAA (G5 (FSAA-LP)). Conclusion CGMP can be a relevant supplement for the treatment of PKU.

Quality of Life Scores Remained Different among the Genotypic Groups of Patients with Suspected Hemochromatosis, Even after Treatment Period

Background: Hemochromatosis is a genetic condition of iron overload caused by deficiency of hepcidin. In a previous stage of this study, patients with suspected hemochromatosis had their quality of life (QL) measured. We observed that QL scores differed among genotypic groups of patients. In this reported final phase of the study, the aims were to compare QL scores after a treatment period of approximately 3 years and to analyze a possible association of the serum ferritin values with QL scores. Methods: Sixty-five patients were enrolled in this final phase and divided into group 1 (patients that showed primary iron overload and homozygous genotype for the HFE p.Cys282Tyr mutation) and group 2 (other kinds of genotypes). Short Form 36 (SF-36) was performed and consisted of eight domains with a physical and also a mental component. Results: Both groups had a significant decrease in serum ferritin concentrations: group 1 had a variation from 1844 ± 1313 ng/mL to 281 ± 294 ng/mL, and group 2 had a variation from 1216 ± 631 ng/mL to 236 ± 174 ng/mL. Group 1 had a smaller mean value for these six SF-36 domains compared with group 2, indicating a worse QL. Conclusions: In this final stage, six domains demonstrated a difference among genotypic groups (role emotional and mental health, adding to the four of the initial phase), reassuring the impact of the identified genotype on the QL of hemochromatosis patients. Furthermore, despite that both patient groups demonstrated similar and significant decreases in serum ferritin values, no association was found between the decrease in this biological parameter and the SF-36 domains.

Improvement of Medical Treatment in Japanese Patients With Metastatic Renal Cell Carcinoma

Background/Aim: To evaluate the relationship between treatment period and overall survival (OS) and to identify clinical factors associated with OS in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Two hundred thirteen consecutive patients with mRCC receiving systemic therapy between 2008 and 2020 were divided into two groups: those starting first-line therapy in 2008-2015 (n=133) and those in 2016-2020 (n=80). Clinical factors associated with OS were retrospectively and statistically analyzed. Results: Median OS and one-, three- and five-year OS rates were not reached and 88.7%, 64.9%, and 64.9% in patients treated in 2016-2020; 31.4 months and 78.5%, 42.8% and 34.2% in 2008-2015 (p=0.0013). Multivariate analysis identified the period in which first-line therapy was started as the strongest predictor for OS (p=0.0002). Conclusion: OS was significantly better in mRCC patients treated in 2016-2020 than in 2008-2015. Treatment period was the strongest predictor for OS.

Impact of Injection Protocol Selection by Retina Specialists on Clinical Outcomes in Patients with Diabetic Macular Edema

Intravitreal anti-VEGF injections are the current gold standard for treating diabetic macular edema (DME). However, injection practice patterns of retina specialists have varied markedly based on physician discretion. This retrospective study analyzes the impact of injection protocol selection on change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) in 170 eyes treated by 4 retina specialists practicing a pro re nata (PRN) strategy between 2010 and 2020. DME patients received an average of 7.25 injections every 6.24 weeks over 56.6 weeks. There were significant differences between retina specialists in mean number of injections (p = 0.0001) and mean length of treatment (p = 0.0007) but not in mean interval between injections. Over the treatment period, average change in BCVA was −0.053 logMAR, and average change in CMT was −51.1 µm, neither of which had significant differences between retina specialists. BCVA and CMT at initial visit were found to be significantly associated with improved BCVA and CMT over the treatment period (p < 0.001). Number of injections administered and interval between injections were not found to be significant factors affecting change in BCVA or CMT. Despite significant differences in injection dosing regimen, retina specialists achieved similar outcomes in change in BCVA and CMT over the treatment period.

Evaluation of musculoskeletal adverse effects in patients on systemic isotretinoin treatment: A cross-sectional study

Objectives: This study aims to investigate the frequency of musculoskeletal adverse effects in acne vulgaris patients receiving systemic isotretinoin treatment. Patients and methods: Between January 2016 and December 2017, a total of 200 severe acne patients (22 males, 178 females; mean age: 21.8±0.4 years; range, 15 to 53 years) who were on isotretinoin treatment were retrospectively analyzed. Data including age, sex, body mass index (BMI), duration of disease, diagnosis, and comorbidities were recorded. Back pain severity was evaluated with the Visual Analog Scale (VAS). Results: The treatment period was mean 8.5±0.1 (range, 6 to 12) months. The dose of isotretinoin was mean 0.6±0.1 (range, 0.5 and 1) mg/kg. Musculoskeletal side effects were seen in 99 (49.5%) patients. Back pain was reported during the treatment period in 78 (78.7%) patients. The diagnosis was mechanical back pain in 31 (39.7%) and inflammatory back pain in 47 (60.3%) patients. The moderate-severe back pain group received higher cumulative isotretinoin doses than the mild back pain group (p=0.003). The BMI values did not show a significant difference between the patients with and without back pain (p=0.55). There was no significant correlation between the BMI and VAS scores (p=0.06). The VAS scores were found to be correlated with age (p=0.04). Sacroiliitis was diagnosed in four (4%) patients. One (1%) patient was diagnosed with enthesitis. Creatine kinase elevation was reported in 18 (18.1%) patients, while three (3%) patients described myalgia of mild severity. Conclusion: Low back pain is one of the most common musculoskeletal side effects of isotretinoin treatment that usually resolves with dose reduction. The cumulative dose of isotretinoin does not seem to play a role in the development of back pain, but can determine pain severity. Pain severity is directly correlated with the increasing age. Evaluation of the patients for musculoskeletal side effects during isotretinoin use is important in clinical practice, as it is a common occurrence.

Removal of selected pesticides, alkylphenols, hormones and bisphenol A from domestic wastewater by electrooxidation process

In this study, seven compounds of environmental and health concern were treated by electrooxidation to determine their removal efficiencies from domestic wastewater. A batch type lab-scale reactor was used for the treatment process, and the analytes studied included two obsolete pesticides, two alkylphenols, two hormones, and bisphenol A. Titanium oxide and graphite electrodes were used as anode and cathode, respectively. Parameters of the electrooxidation process including pH of wastewater, ionic strength, applied current and treatment period were optimized by the univariate approach to maximize the removal efficiency of the analytes from wastewater. The optimum conditions were determined as nonadjusted pH of wastewater, 1.5 A current, 15 min treatment period and 5.0 g/L sodium chloride. Dispersive liquid-liquid microextraction was used to preconcentrate analytes before and after treatment in order to calculate the removal efficiency of analytes. The removal efficiency obtained under the optimum conditions was satisfactory for all seven analytes at different influent concentrations.

Profitability and Financial Leverage: Evidence from a Quasi-Natural Experiment

The relationship between profitability and leverage is controversial in the capital structure literature. We revisit this relation in light of a novel quasi-natural experiment that increases market power for a subset of firms. We find that treated firms increase their profitability throughout the treatment period. However, they only transiently reduce financial leverage, gradually reverting to their preshock level. Firms respond differently according to size with large firms gradually adjusting their leverage toward a new target and small firms reducing it. The patterns are broadly consistent with dynamic trade-off models with both fixed and variable adjustment costs. This paper was accepted by Gustavo Manso, finance.

Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial

Background Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions The 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. Trial registration ClinicalTrials.gov NCT03934931.