Mandibular overdenture retained by four one-piece titanium-zirconium mini implants: A 2-year follow-up on prosthodontic outcomes.

OBJECTIVE: This 2-year prospective study reports the incidence of prosthetic complications and maintenance events after treatment with mandibular overdenture retained by four mini implants opposed to a maxillary denture. METHODS: Implant intervention included flapless or flapped surgery combined with immediate or delayed loading, as part of a randomized clinical trial. Four one-piece titanium-zirconium mini-implants (Straumann Mini Implant System) were inserted, and the retentive PEEK elements (Optiloc) were incorporated into the overdenture using chairside procedures. Prosthodontic complications and maintenance events were recorded over a 2-year follow-up, and the final outcome was defined according to standardized criteria. Data analysis included descriptive statistics, incidence and incidence density rates, and Kaplan-Meier survival. RESULTS: 73 out of 74 patients (64.9 % female), mean age of 64 (SD=8.2) years, completed the study follow-up (one withdrew after 9 months). Implant survival was 100 %. A total of 163 prosthodontic events occurred in 53 patients (72.6 %), and 20 patients had no clinical complaints or maintenance needs. The most common procedures were adjustment/repair of the overdenture base (47.0 %), replacement of retentive inserts (19.8 %), and laboratory relining (12.9 %). A high prosthodontic success rate was achieved (93.2 %), and all patients presented serviceable overdentures and continuous use after the resolution of prosthodontic complications. The incidences of matrix replacement and laboratory relines were low in the first year, while denture base adjustments were common within the first year, especially in the first 6 months. CONCLUSION: The mini implant system showed high prosthodontic success rates. Minor adjustments/repairs during the initial follow-up were common. Relines and matrix replacements tend to occur after one year of overdenture use, and matrix replacements may occur as a consequence of the need for relining.

Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs-a pilot study.

Introduction: Cannabinoids show great therapeutic potential, but their effect on anesthesia still remains unclear. Use of chronic recreational Cannabis in humans undergoing anesthetic procedures tends to require a higher dose when compared to non-users. On the other hand, studies on rodents and dogs have shown that cannabinoid agonists may potentiate certain anesthetics. This contrast of effects possibly occurs due to different time lengths of administration of different phytocannabinoids at different doses, and their distinct effects on the Endocannabinoid System, which is also affected by anesthetics such as propofol and isoflurane. Methods: Twenty-seven healthy male dogs, client-owned, ranging from 1 to 7 years, and from 5 to 35 kg were selected, mean weight 15.03±7.39 kg, with owners volunteering their animals to participate in the research performed in the Federal University of Santa Catarina (UFSC). Dogs were randomized into 3 groups. The Control Group (CON, n = 9), receiving only Extra Virgin Olive Oil, the same oil-base used in the treatment groups. Group 2 (G2, n = 9) received 2 mg/kg of total phytocannabinoids, and Group 3 (G3, n = 9) received 6 mg/kg of total phytocannabinoids. All groups received their treatments transmucosally, 75 min before their induction with propofol. Heart and respiratory rate, blood pressure, temperature and sedation were evaluated prior to, and at 30, 60, and 75 min after administration of the fsCBD-rich extract or Placebo extract. Preanesthetic medication protocol was also included across all treatment groups, 15 min before induction. Parametric data was analyzed with one-way ANOVA, followed by Student-Newman-Keuls (SNK) if significant statistical differences were found. Non-parametric data was analyzed using Friedman's test, followed by Dunn test for comparisons between all timepoints in the same group. Kruskal-Wallis followed by Dunn was utilized for between groups comparisons. Propofol dose necessary for induction was analyzed through One-way ANOVA followed by Tukey's Multiple Comparisons Test, using Instat by Graphpad, and differences were considered statistically significant when p < 0.05. Our analysis assessed if statistical significance was present between time points in the same group, and between groups in the same time points. Results: In our study, 6 mg/kg of total phytocannabinoids were able to reduce the dose of propofol necessary for induction by 23% when compared to the control group. The fsCBD-rich extract did not produce significant sedation within or between groups, although statistically significant differences in heart rate and systolic blood pressure were found. Discussion: Our findings indicate that phytocannabinoids could be an adjunct option in anesthesia, although further research is necessary to better confirm this data. Additionally, further research is needed to determine the best dosage, delivery method, time for administration, ideal molecular profile for desired effects, safety, drug-drug interactions, and transurgical effects.

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts.

The development of cosmetic formulations with moisturizing and film-forming properties has been very important to help keep skin physiology and protection. In this context, this study aimed to develop a cosmetic formulation containing Tara gum and Brazilian berry extract and evaluate its physical-mechanical, film-forming, and sensory properties. A gel formulation was developed based on Tara gum added to Plinia cauliflora extract and was characterized by its spreadability profile and sensory properties. A clinical study was carried out with ten participants to evaluate the skin microrelief, stratum corneum water content, transepidermal water loss (TEWL), and skin morphological characteristics by reflectance confocal microscopy (RCM) before and after 2 h of application of the formulations. The formulation with Brazilian berry significantly decreased the work of shear parameter, which can be correlated with improved spreadability in the sensory analysis. The clinical study showed that both formulations improved skin hydration and reduced the TEWL. The RCM imaging analysis showed the visible film on the skin surface, a decrease in the size of furrows, an increase in the reflectance of the interkeratinocytes, and reflectance of the stratum corneum for both formulations. These results were more pronounced for the formulation containing Brazilian berry. The Tara gum in the gel formulation promoted the formation and visualization of a polymeric net on the stratum corneum surface, demonstrated by the images obtained from RCM. However, the formulation added with the Brazilian berry extract improved the skin microrelief, honeycomb pattern of the epidermis, and skin hydration in deeper layers of the epidermis.

Glial-restricted progenitor cells: a cure for diseased brain?

The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.

Glial-restricted progenitor cells: a cure for diseased brain?

The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.

Soluble epoxide hydrolase inhibitors for smoking-associated inflammatory lung diseases and chronic obstructive pulmonary disease: a meta-analytical systematic review of preclinical and clinical studies.

An evaluation of the inflammatory enzymatic interactions related to pulmonary function can help identify biomarkers for interventions or prophylactic measures to improve patient prognosis. This study aimed to determine the effect of epoxide hydrolase inhibition by GSK2256294 in different pulmonary inflammation models. A secondary search was performed using Medline/PubMed, Web of Science, SciELO, Cochrane Library, Embase, Academic Google, and gray literature by two independent reviewers, who analyzed the methodological quality and consistency of the data. Different variables were compared using a meta-analysis. A total of 86 studies were found, 4 of which were selected from the gray literature. Based on the eligibility criteria, two clinical and one preclinical studies were evaluated. GSK2256294 inhibited the soluble epoxide hydrolase enzyme in both clinical and preclinical models, exhibiting greater effectiveness in clinical studies and contributing to the anti-inflammatory activity mediated by the eicosatrienoic pathway by reducing the levels of dihydroxyeicosatrienoic acids and leukotoxin-diol. Overall, GSK2256294 was identified as a promising drug for controlling the deleterious manifestations of lung inflammation. Further clinical and preclinical studies are required to ensure consistency among the evidence and identify other biological activities mediated by GSK2256294.

Four single implant-supported crowns replacing the maxillary incisors: A retrospective report of 10 cases with 2-9 years of follow-up.

OBJECTIVE: This retrospective case series aimed to assess the stability of the papilla around four single crowns supported by narrow-diameter implants replacing all maxillary incisors. Secondary objectives included assessment of marginal bone level stability, incidence of technical and biological complications, and patient satisfaction. MATERIALS AND METHODS: Individuals with four adjacent implants in maxillary incisor sites, placed with a 3 mm inter-implant distance and rehabilitated with single crowns were included. Retrospective data were obtained from photographs and radiographs taken at the delivery of the prosthesis (baseline-T0). Patients were then recalled (≥2 years after T0) for clinical and radiographic examination (follow-up-T1). Photographs were obtained and patient satisfaction was assessed using a visual analogue scale. Papilla height and marginal bone level were compared over time. RESULTS: Data from 10 patients with medium-low smile lines and rehabilitated with 40 implants, in function for 5.4 ± 1.9 years, were analyzed. The papilla height between implants (T0: 2.3 ± 0.9 mm; T1: 2.6 ± 0.7 mm; p = .011) and between tooth and implant (T0: 3.4 ± 0.9 mm; T1: 3.8 ± 0.8 mm; p = .025) increased significantly over the years. The marginal bone level remained stable over time (T0: 0.88 ± 0.57 mm; T1: 0.71 ± 0.67 mm; p = .007). Patients were highly satisfied (97.7 ± 0.3%) with the treatment outcome. CONCLUSION: Within its limitations, this study demonstrated that four single implant-supported crowns placed at maxillary incisor sites may exhibit soft tissue and marginal bone stability over a long period of time. This treatment approach, however, should be restricted to few patients as it requires a proper case selection and skillful execution of all surgical and prosthetic steps.

The Prevalence and Severity of Dental Caries Among Pregnant Women in the State of Rio de Janeiro, Brazil.

AIM: To assess in a pilot study the prevalence and severity of dental caries among pregnant women compared to non-pregnant women in the state of Rio de Janeiro, Brazil. MATERIALS AND METHODS: A cross-sectional, observational study was conducted. Data collection consisted of clinical examinations and general questionnaires concerning oral hygiene habits and recent dental visits of pregnant and non-pregnant women. Prevalence and severity of caries was determined by the CAST index and the CAST severity score. Permission for this study was granted by the National Research Ethics Commission of Brazil. Written informed consent was obtained from all participants. RESULTS: In total, 67 pregnant women were included (mean age (SD) 25.5 ± 5.4 years) and 79 non-pregnant women (26.0 ± 5.3 years). Mean number of teeth with untreated caries (CAST 4-7) among pregnant women was significantly lower (1.2 ± 1.8) compared to non-pregnant women (2.7 ± 4.0; Mann-Whitney test, p = 0.027). In both groups, 40-60% were in need of curative treatment. There was no significant difference between the two groups in frequency of dental visits (p > 0.05), but pregnant women brushed their teeth more often (Mann-Whitney test, p < 0.001). CONCLUSION: Pregnant women in the state of Rio de Janeiro have fewer untreated caries and less severe dental caries compared to non-pregnant women. Still, half of all women in this study are in need of curative treatment for at least one tooth. Effective preventive programs should therefore be developed to stimulate preventive oral care among all women.

Retromolar canal diagnosed by cone-beam computed tomography and its influence in inferior alveolar nerve block / Canal retromolar diagnosticado por tomografía computarizada de haz cónico y su influencia en el bloqueo del nervio alveolar inferior

The aim of this study was to observed the anesthetic efficacy of the alveolar nerve block on nine patients that CBCT diagnosed unilateral retromolar canal on a double-blind, split-mouth approach. The assessments of patient response to thermal (pulp vitality test) and pressure (compression of soft tissue) stimuli were carried out before and 5 minutes after the inferior alveolar nerve block procedure, using both visual analog scale (VAS) and Mc Gill pain questionnaires (McG). The mean percentage of patient response decreased after alveolar nerve block, according to both VAS and McG, and was statistically similar among hemi mandibles with and without retromolar canal (Wilcoxon>0.05); however, those without retromolar canal presented greater reduction in patient response in 6 out of 9 cases. Therefore, the retromolar canal is not a determinant factor of inferior alveolar nerve block failure.

El objetivo de este estudio fue observar la eficacia anestésica del bloqueo del nervio alveolar en nueve pacientes que CBCT diagnosticó canal retromolar unilateral en un abordaje de boca dividida doble ciego. Las evaluaciones de la respuesta del paciente a los estímulos térmicos (prueba de vitalidad pulpar) y de presión (compresión de los tejidos blandos) se realizaron antes y 5 minutos después del procedimiento de bloqueo del nervio alveolar inferior, utilizando tanto la escala analógica visual (VAS) como los cuestionarios de dolor de Mc Gill ( McG). El porcentaje medio de respuesta de los pacientes disminuyó tras el bloqueo del nervio alveolar, según EVA y McG, y fue estadísticamente similar entre hemimandíbulas con y sin canal retromolar (Wilcoxon>0,05); sin embargo, aquellos sin canal retromolar presentaron mayor reducción en la respuesta del paciente en 6 de 9 casos. Por lo tanto, el canal retromolar no es un factor determinante del fracaso del bloqueo del nervio alveolar inferior.

Caracterización clínico-epidemiológica de pacientes pediátricos con intento suicida en el Hospital Pediátrico Provincial de Holguín

Fundamento los intentos de suicidio en edades pediátricas son un problema actual con tendencia creciente a nivel mundial. Este grupo es muy vulnerable a la acción de factores internos y externos que alteran su integridad. En Cuba, a pesar de los logros obtenidos en ese sentido, también se considera como un problema de salud mental. Objetivo caracterizar desde el punto de vista clínico y epidemiológico a pacientes pediátricos con intento suicida. Métodos se realizó un estudio descriptivo, retrospectivo y de corte transversal, en el Hospital Pediátrico Provincial Octavio Concepción y de la Pedraja, de la provincia de Holguín, en el periodo enero/2020-diciembre/2021. Se trabajó con la totalidad del universo, conformado por 397 pacientes atendidos en la institución hospitalaria por intento suicida en el periodo de estudio. Las variables estudiadas fueron: edad, sexo, procedencia y método utilizado. Se empleó la estadística descriptiva. Resultados predominaron los pacientes con edades entre 16 y 18 años (48,4 %), del sexo femenino (74,6 %) y de procedencia urbana (70,3 %). El 92,2 % utilizó como método de suicidio la ingestión de psicofármacos. Conclusiones las variables estudiadas se comportan de forma similar a lo descrito en otras poblaciones y contextos, en los cuales también predominaron las adolescentes de procedencia urbana que ingirieron psicofármacos.

Background suicide attempts in pediatric ages are a current problem with a growing trend worldwide. This group is very vulnerable to the action of internal and external factors that alter their integrity. In Cuba, despite the achievements in this regard, it is also considered a mental health problem. Objective to characterize, from the clinical and epidemiological point of view, pediatric patients with suicide attempts. Methods a descriptive, retrospective and cross-sectional study was carried out at the Octavio Concepción y de la Pedraja Provincial Pediatric Hospital, in the Holguín province, from January/2020 to December/2021. The entire universe was analyzed made up of 397 patients, treated at the hospital for suicide attempts during the studied period. The variables were: age, sex, origin and method used. Descriptive statistics were used. Results patients aged between 16 and 18 years old (48.4%), female (74.6%) and urban origin (70.3%) predominated. 92.2% used the ingestion of psychotropic drugs as a method of suicide. Conclusions the studied variables behave in a similar way to that described in other populations and contexts, in which adolescents from urban origin who ingested psychoactive drugs also predominated.

Influence of partially exposed nonabsorbable membrane for alveolar ridge preservation: A randomized controlled trial.

AIM: This randomized controlled trial evaluated the impact of a partially exposed non-absorbable membrane (dPTFE) in Alveolar Ridge Preservation (ARP) procedures on clinical, tomographic, immunoenzymatic, implant-related, and patient-centered outcomes. MATERIALS AND METHODS: Patients with a hopeless maxillary single-rooted tooth demanding rehabilitation with implants were included. Patients were randomized into two groups: dPTFE (n = 22)-tooth extraction followed by ARP using a partially exposed dPTFE membrane; USH (n = 22)-unassisted socket healing. Clinical and tomographic analyses were performed at baseline and after 3 months. After 3 months, patients received one dental implant. Implant stability quotient was obtained following implant placement. Bone-related markers were analyzed in bone biopsies using an immunoenzymatic assay. RESULTS: Greater gain in Keratinized Mucosa Width (KMW) was observed in the dPTFE (1.33 ± 0.98 mm) compared to USH (0.59 ± 0.98 mm) (Mann-Whitney test, Z = 2,28, p < 0.05). USH showed a reduction of pain/discomfort, edema, and interference with daily life from the seventh day (Friedman/Wilcoxon test, maxT = 7.48, 8.00, and 5.92, respectively, p < 0.05). dPTFE presents a reduction of edema and interference with daily life from the 7th day and pain/discomfort from the 14th day (Friedman/Wilcoxon test, maxT = 5.40, 5.26, and 4.78, respectively, p < 0.05). The dPTFE group presented higher pain/discomfort in the 35 and 42 days and higher edema from 7 to 42 days postoperatively than USH group (Mann-Whitney test, p < 0.05). No differences between groups were observed in the tomographic measures, immunoenzymatic analysis, and implant stability (p > 0.05). CONCLUSION: dPTFE was superior to USH by increasing KMW gain. However, dPTFE without bone graft presented similar bone loss compared to USH. This clinical trial was not registered prior to participant recruitment and randomization (NCT04329351).

Development of multifunctional sunscreens: Evaluation of physico-mechanical and film-forming properties.

The exposome consists of several factors such as solar radiation and pollution, which can provoke skin damage and lead to premature skin aging. Thus, the use of multifunctional sunscreens is critical in order to prevent this damage. In addition, film formation is very important to reach the expected SPF. Within this context, the objective of the present study was to develop and evaluate the in vivo SPF, sensory, physico-mechanical, and film-forming properties of sunscreens containing a biopolymer from Tara and red algae. A clinical study of the film-forming effect and of skin hydration was performed by instrumental measurements and by biophysical and skin imaging techniques. The SPF of both formulations, with or without the biopolymer, was 45.6. This result was 10.09% higher than expected. higher than expected. However, the sunscreen added to the biopolymer showed better sensory and texture properties, significantly increased skin hydration and reduced transepidermal water loss. The film-forming property was observed by the analysis of Reflectance Confocal Microscopy images 2, 4, and 6 h after formulation application, and this result was more pronounced for the sunscreen added to the biopolymer. Thus, the film-forming property of the biopolymer was important for prolonging the skin barrier function due to film formation and to obtain more effective and multifunctional sunscreens that provide longer protection.

Randomized Clinical Trial Comparing Insertion Torque and Implant Stability of Two Different Implant Macrogeometries in the Initial Periods of Osseointegration.

Objectives: The present study compared two implants with different macrogeometries placed in healed alveolar sites, evaluating the insertion torque (ITV) and implant stability quotient (ISQ) values at three different periods. Methods: Seventy patients with a total of 100 dental implants were allocated into two groups (n = 50 per group): DuoCone implants (DC group) that included 28 implants in the maxilla and 22 in the mandible, and Maestro implants (MAE group) that included 26 in the maxilla and 24 in the mandible. The ITV was measured during the implant placement, and the ISQ values were measured immediately at implant placement (baseline) and after 30 and 45 days. Results: The mean and standard deviations of the ITV were statistically significant (p < 0.0001), 56.4 ± 6.41 Ncm for the DC group and 29.3 ± 9.65 Ncm for the MAE group. In the DC group, the ISQs ranged between 61.1 ± 3.78 and 69.8 ± 3.86, while the MAE group presented similar values compared with the other group, ranging between 61.9 ± 3.92 and 72.1 ± 2.37. Conclusions: The value of implant insertion torque did not influence the ISQ values measured immediately after implant placement. However, the ITV influenced the ISQ values measured in the two initial periods of osseointegration, with implants installed with lower torques presenting higher ISQ values.

Prosthodontic outcomes of mandibular overdenture treatment with one or two implants: 4-year results of a randomized clinical trial.

OBJECTIVE: To assess the incidence of prosthodontic maintenance events and complications during 4 years of follow-up after mandibular overdenture treatment with one or two implants. METHODS: Participants received one or two implants inserted in the midline (1-IOD group) or the lateral incisor-canine area bilaterally (2-IOD group). Implants were loaded with an early loading protocol after 3 weeks. Programmed recall visits were scheduled at the 6-, 12-, 36-, and 48-month follow-ups and nonprogrammed visits in case of prosthodontic complaints. The type of maintenance was registered, and the final treatment outcome was classified as successful, surviving, unknown, dead, repair, or retreatment. RESULTS: Forty-seven participants, mean age 65.4 ± 8.6, 74.5% female, were included (1-IOD = 23; 2-IOD = 24) and 44 completed the 4-year follow-up. A total of 159 prosthodontic maintenance events occurred and 89 in unscheduled visits. The most common event was the need for minor modifications of the denture base due to sore spots in the oral mucosa (n = 56 in 31 patients), matrix activation (n = 54 in 34 patients), and overdenture fracture (n = 25 in 18 patients). A "successful" or "surviving" outcome could be attributed to 57.5% of cases, whereas 38.3% needed repair. No significant differences in the incidence of prosthodontic events or treatment outcomes were found between the two groups. CONCLUSIONS: Findings show that 1-IODs perform similar to 2-IODs when considering the incidence of fractures and the need for prosthodontic maintenance, including adjustments of the overdenture and the attachment system.

Mandibular bone characteristics, drilling protocols, and final insertion torque for titanium-zirconium mini-implants for overdentures: A cross-sectional analysis.

OBJECTIVE: The aim of this study was to assess the final insertion torque values achieved using site-specific drilling protocols for a novel mini implant system for removable complete overdentures. Anatomical and technical factors influencing final insertion torque were recorded and analyzed. MATERIAL AND METHODS: Participants were randomized to two surgical protocol groups (flapped or flapless) and all received four mini implants (Straumann® mini implant system; Straumann AG) in the anterior mandible, using a 1.6 mm needle drill and a 2.2 mm pilot drill for the implant bed site preparation. The final insertion torque was recorded as the main outcome variable during surgery. Bone type, radiographical bone density, ridge form, implant length, and the drilling protocol were considered as independent variables. Descriptive statistics, generalized estimating equations (GEE) regression, and heatmap charts were used for data analyses. RESULTS: A total of 296 mini implants were placed in 74 patients (mean age = 64.1 ± 8.0; 64.9% female) using flapless (n = 37) or flapped (n = 37) surgeries. Mean final insertion torque was 55.8 ± 18.4 Ncm (10.5% > 35 Ncm, 48.9% between 35 and 65 Ncm, and 40.6% > 65 Ncm). The needle drill was used in only 43.9% of the implant bed sites. Higher final torque values were observed for higher bone densities (bone type I > II > III, and D1-D2 > D3-D4), highly resorbed ridge forms (5-6 > 3-4), flapped surgeries, and male patients. However, regression models showed that the likelihood of achieving optimal insertion torque (≥35 and ≤65 Ncm) was higher for females (OR = 2.14; 95%CI = 1.14-4.01; p = 0.018), ridge forms 3-4 (OR = 2.87; 95%CI = 1.05-7.85; p = 0.040), and flapless surgeries (OR = 1.96; 95%CI = 1.09-3.51; p = 0.024). CONCLUSIONS: Sufficient primary stability for immediate loading was achieved for the majority of the mini implants placed. Surgical implant bed preparation should be site-specific to achieve optimal primary stability for immediate loading while avoiding excessive insertion torque.

Add-on treatment with Cerebrolysin improves clinical symptoms in patients with ALS: results from a prospective, single-center, placebo-controlled, randomized, double-blind, phase II study.

Amyotrophic lateral sclerosis (ALS) is a devastating and progressive neurodegenerative disease with limited treatment options available. Cerebrolysin is a drug candidate for the treatment of ALS because of its neuroprotective and neuroregenerative effects. We initiated a pilot clinical study of a combination of Cerebrolysin and riluzole to assess the therapeutic benefit of Cerebrolysin as an add-on treatment on clinical signs and symptoms in outpatients with ALS. Twenty patients with a clinically definitive diagnosis of ALS were enrolled and randomly assigned in a 1:1 ratio to receive Cerebrolysin or placebo. All patients received 50 mg of riluzole PO twice daily as a standard treatment. Patients in the Cerebrolysin group received intravenous injections of 10 mL of Cerebrolysin once daily, five days a week for the first month and three days a week for the next two months. Analysis of the ALS Functional Rating Scale - revised at Month 1 (primary outcome measure), showed a significant treatment effect in favor of Cerebrolysin with a 2.3-point improvement from baseline to Month 1 compared to a 0.9-point decrease in patients on placebo (P=0.005). The effect was maintained over the three-month study period, and the beneficial effect of Cerebrolysin over placebo was also evident in the secondary outcome measures. The safety analysis showed that the combination of riluzole and Cerebrolyisn was well tolerated. Our results demonstrate for the first time a significant clinical effect of Cerebrolysin in improving functional outcomes in patients with ALS and suggest that Cerebrolysin has potential as a novel therapeutic option for ALS.

Translating the determinant aspects on the study design in the dental implant field.

Objective: In this article, we analyzed the important categories capable of interfering with the determinants of scientific advancement in the type of study, considering seven leading journals over a 20-year. Methodology: A bibliometric review was performed at the website of well-established implant dentistry journals in five-time points defined to represent a 20-year period of observation. The measures associated with the type of study design were: the country of origin of the article, country income, continent of the corresponding author, inter-institutional collaboration, interdisciplinary collaboration, type of funding, and topic of research. Logistic regression was used in the multiple models to identify the exploratory factors associated with the type of study. Results: From a total of 1,944 articles, 50.6% comprised clinical studies. High-income countries and continents stood out for developing more clinical research than others. Since research funders request more collaborative research, overall clinical studies depended upon more inter-institutional collaboration than the others. Most clinical studies were partly supported by research institutes or universities and by industry. About the research topic, the majority of the clinical and animal studies disclosed surgical procedures. Conclusions: High-income countries and continents are more likely to develop clinical studies in the surgical procedures field. The highest collaborations in terms of the number of institutions and funding sources are more prevalent in clinical research designs. Indeed, most in vivo studies in dental implant fields are performed to evaluate new materials or even new surgical procedures.

Ethical considerations on placebo-controlled vaccine trials in pregnant women / Consideraciones éticas sobre los ensayos de vacunas controlados con placebo en mujeres embarazadas / Considerações éticas sobre estudos de vacina controlada com placebo em gestantes

Abstract Placebo use in clinical trials, whenever a proven effective treatment exists, is one of the most debated topics in contemporary research ethics. This article addresses the ethical framework for placebo use in clinical trials assessing vaccine efficacy in pregnant women. Vaccine trial participants are healthy at the outset and some must be infected during the study to demonstrate the product's efficacy, meaning that placebo-treated participants are under risk of serious and irreversible harm. If effective vaccines exist, such risk precludes placebo use. This interdiction should be extended to any clinical trial of vaccine efficacy in pregnant women, because a demonstration of clinical efficacy in nonpregnant individuals and comparable immunogenic responses in pregnant women are predictors of efficacy in pregnancy as well. Moreover, product effectiveness in real-world use scenarios can be ascertained by observational studies conducted after its inclusion in vaccination campaigns.

Resumen El uso de placebo en ensayos clínicos es uno de los principales temas debatidos sobre la ética en investigación contemporánea cuando existe un tratamiento eficaz probado. Este artículo aborda la ética en el uso de placebo en ensayos clínicos sobre la eficacia de vacuna en mujeres embarazadas. Las participantes en los ensayos de vacunas estaban sanas al inicio del estudio, y algunas fueron vacunadas durante el estudio para demostrar la eficacia del producto. Las participantes tratadas con placebo corren el riesgo de sufrir daños graves e irreversibles. Si existen vacunas efectivas, este riesgo impide el uso de placebo. Este impedimento debe extenderse a cualquier ensayo clínico de eficacia de vacuna en embarazadas, pues la eficacia clínica demostrada en mujeres no embarazadas y las respuestas inmunogénicas comparables con las embarazadas son predictores de eficacia en el embarazo. Además, la efectividad del producto se constata en estudios observacionales realizados tras las campañas de vacunación.

Resumo O uso de placebo em ensaios clínicos, quando um tratamento comprovadamente eficaz existe, é um dos principais tópicos debatidos na ética em pesquisa contemporânea. Este artigo aborda o quadro ético para o uso de placebo em ensaios clínicos que avaliam a eficácia de vacina em gestantes. Participantes em ensaios de vacina são saudáveis no início e alguns devem ser inoculados durante o estudo para demonstrar a eficácia do produto. Ou seja, participantes tratados com placebo estão sob risco de danos graves e irreversíveis. Se existirem vacinas eficazes, esse risco impede o uso de placebo. Essa interdição deve ser estendida a qualquer ensaio clínico de eficácia de vacina em gestantes, pois a demonstração de eficácia clínica em não gestantes e as respostas imunogênicas comparáveis em gestantes também são preditoras de eficácia na gravidez. Ademais, a eficácia do produto em cenários reais de uso pode ser verificada por estudos observacionais realizados após sua inclusão em campanhas de vacinação.

Esclerose lateral amiotrófica em Belo Horizonte, Brasil entre 2010 e 2020: um estudo clínico epidemiológico / Amyotrophic lateral sclerosis in Belo Horizont, Brazil between 2010 and 2020: a clinical epidemiological study

Objetivo: Descrever o perfil clínico de indivíduos com Esclerose Lateral Amiotrófica (ELA) de um hospital de referência na cidade de Belo Horizonte, Brasil. Métodos: Trata-se de um estudo transversal retrospectivo com coleta de dados de prontuários eletrônicos de indivíduos com diagnóstico definido de ELA entre 2010 e 2020, no setor de referência em Distrofias Musculares de um hospital de uma capital brasileira. Resultados: Foram incluídos 103 indivíduos com ELA, com idade média de 60±12 anos, idade média de diagnóstico de 56±12 anos e tempo médio de evolução da doença de 3±3 anos. Além disso, 70% eram do sexo masculino, 88% com ELA esporádica, com envolvimento bulbar semelhante entre leve (32%), moderado (27%) e grave (28%), e com maior taxa de diagnóstico de 50 a 70 anos de idade. Conclusão: Os dados epidemiológicos deste estudo são muito semelhantes aos da literatura. No entanto, a heterogeneidade da doença, a complexidade do diagnóstico e a diversidade de formas que cada estudo traz para a doença, e principalmente a rápida progressão, dificultam a discussão de um quadro mais extenso. Traçar esse perfil é importante para uma clínica mais focada e um manejo mais adequado, e para isso são necessários mais estudos.

Objective: To describe the clinical profile of individuals with Amyotrophic Lateral Sclerosis (ALS) from a reference hospital in the city of Belo Horizonte, Brazil. Method: This is a retrospective cross-sectional study with data collection from electronic medical records of individuals with a defined diagnosis of ALS between 2010 and 2020, in the Muscular Dystrophies reference sector of a hospital in a Brazilian capital. Results: A total of 103 individuals with ALS were included, with a mean age of 60±12 years, mean diagnostic age 56±12 years, and mean time of disease progression of 3±3 years. Furthermore, 70% were male, 88% with sporadic ALS, with a similar bulbar involvement between mild (32%), moderate (27%) and severe (28%), and with a higher rate of diagnosis from 50 to 70 years of age. Conclusion: The epidemiological data from this study are very similar to those in the literature. However, the heterogeneity of the disease, the complexity of the diagnosis and the diversity of forms that each study brings to the disease, and especially the rapid progression, make a more extensive picture difficult to be discussed. Tracing this profile is important for a more focused clinic and a more adequate management, and for that, further studies are needed.