Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Did physical aggression in women increase during the novel coronavirus 2019 (COVID-19) pandemic? A perspective of facial trauma.

PURPOSE: The present study aimed to assess whether there was an increase in physical aggression in women treated in Belo Horizonte, Minas Gerais, through the mandatory quarantine. METHODS: Data from a cross-sectional study were collected and analyzed, from March 1 to December 31, 2020. Additionally, data from the same period the previous year were collected for comparison. RESULTS: Of the etiologies reviewed for 2020, physical aggression had the highest percentage increase (+ 4.9%) and was the only etiology that showed a significant difference (p = 0.045). The mean age of the included patients was 34.05 years in 2019 and 33.97 in 2020, and most of the women had facial fractures, with nasal fractures being the most frequent, followed by jaw fractures. There was a significant increase (p = 0.34) in the conservative treatment of fractures from 2019 (48.6%) to 2020 (71.7%) and a minor (p = 0.088) increase in aggression toward intimate partners (2019, 40.9%; 2020, 63.9%). CONCLUSION: Physical aggression against women increased during the period of mandatory social isolation that resulted from the COVID-19 pandemic. Health professionals, including emergency services professionals, must be trained to identify victims and refer them to specialized care.

New Device for Submental Endotracheal Intubation: A Prospective Cohort Study.

PURPOSE: Silveira et al (2020) described a new device that aims to facilitate submental intubation. This study aimed to verify the clinical complications from using this new device for submental endotracheal compared to the conventional technique. MATERIAL AND METHODS: Patients who underwent submental intubation with the orotracheal tube transposition device were compared to those who underwent the conventional technique in a prospective cohort study. The primary predictor variable was intubation technique: conventional versus device-assisted. The primary outcome was total complications (all complications trans and postoperative, were recorded). Secondary variables were 1) age, 2) sex, 3) etiology, 4) race/ethnicity, 5) fracture types, and 6) intubation procedure time. The data were analyzed using descriptive and inferential statistics. Differences were considered statistically significant at P < .05. RESULTS: Forty-two cases are described, including 24 cases with the device and 18 cases using the conventional technique. The mean age was 30.5 ± 11.228 years. The majority of patients were of male sex (88%), non-white (64%), and victims of motorcycle accidents (33%). The mean time to perform submental intubation was 9.9 minutes (±2.1293). Nine complications were recorded, including 2 intraoperative (2 tube dislocations) and 7 postoperative (5 unesthetic scars, one localized hematoma, and one skin infection). The technique used did not affect the time to submental intubation (P = .610). There was no association between technique and occurrence of intraoperative (P = .679; RR = 0.75; confidence interval [CI], 0.05-11.2), postoperative (P = .656; RR = 1.000; CI, 0.255-3.922), or total complications (P = .602; RR = 0.938; CI, 0.293-3.003). CONCLUSION: The new device proposed seems to be a good option with similar complication rates as compared to conventional submental intubation.

Profile of patients with TMJ dislocation in a level-1 emergency hospital: A cross-sectional study.

OBJECTIVE: To describe a cross-sectional study of TMJ dislocation in a Brazilian level-one trauma center. METHODS: The data were collected and analyzed from electronic medical records in a period from 2013 to 2020. RESULTS: Bilateral TMJ dislocation occurred in the majority of cases, being reduced by the Nélaton maneuver associated with Barton's bandage. The average time between the dislocation and specialist appointment was 30.69 hours. Elderly patients were associated with an increased number of recurrent dislocations (p = 0.03). Furthermore, a longer dislocation time was associated with the reduction under intravenous (IV) sedation (p < 0.05). CONCLUSION: The literature is still scarce concerning demographic data, treatment modalities, and follow-up. More studies are necessary to better understand TMJ dislocation management.

Aspiration of dental items: Case report with literature review and proposed management algorithm.

The aim of this present study is to describe a case of a screwdriver implant aspiration removed with flexible bronchoscopy. This study reviewed the current literature and the authors also proposed an airway management algorithm in case of suspected foreign body aspiration during dental procedures. A review of English-language literature of aspiration of objects after clinical dental practice from 1984 to 2021 was performed. The bronchoscopy was the main method for dental items removal. A total of 57 cases from the literature were enrolled in this study. Aspiration of dental crown and prostheses (43.85%) followed by implant material (19.29%) and tooth (15.78%) were the main aspirated items. Prevention is the better way to avoid this type of complication. Early diagnosis facilitates the removal of foreign body and bronchoscopy is considered the treatment of choice for removal of foreign body aspiration. Also, regular professional training in basic life support is required.

Analysis of the energy balance and CO2 flow under the influence of the seasonality of climatic elements in a mangrove ecosystem in Eastern Amazon.

An unprecedented study was carried out in a mangrove ecosystem in the northeastern coast of the Brazilian Amazon to understand the behavior of climatic elements in a year with the occurrence of El Niño (2015), associated with the seasonal function source/sink of CO2 by the ecosystem. Global radiation (Rg), net radiation (Rn), temperature, relative humidity, precipitation, horizontal wind speed and direction, as well as turbulent flows of sensible heat (H), latent heat (LE), and carbon (f_CO2) were recorded using eddy covariance, a system for studying turbulent flows of heat and gases in the atmosphere. We observed a drastic reduction in rainfall volumes, which accounts for 63.7% of the expected total according to the region's climatology. Regarding f_ CO2, the highest values of photosynthesis, autotrophic, and heterotrophic respiration of the ecosystem occurred in the wet season due to precipitation, ideal photosynthetically active radiation, lower soil salinity, and higher NDVI of the ecosystem. In the 2nd semester of the year, we observed that the decrease in cloudiness, causing a higher radiation supply in the forest canopy, accompanied by a reduction in precipitation and an increase in the value of H and soil salinity, favored the increase of foliar abscission by the dominant genus Rhizophora and Avicennia, thus influencing the reduction of magnitudes of carbon source/sink functions in the ecosystem during this season, even on high tide days.

ATX-MS-1467 Induces Long-Term Tolerance to Myelin Basic Protein in (DR2 × Ob1)F1 Mice by Induction of IL-10-Secreting iTregs.

INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion. METHODS AND RESULTS: Our study extends these observations to show that subcutaneous treatment with 100 µg of ATX-MS-1467 after induction of EAE in the same mouse model reversed established clinical disability (p < 0.0001) and histological markers of inflammation and demyelination (p < 0.001) compared with vehicle-treated animals; furthermore, in longitudinal magnetic resonance imaging analyses, disruption of blood-brain barrier integrity was reversed, compared with vehicle-treated animals (p < 0.05). Chronic treatment with ATX-MS-1467 was associated with an enduring shift from a pro-inflammatory to a tolerogenic state in the periphery, as shown by an increase in interleukin 10 secretion, relative to interleukin 2, interleukin 17 and interferon γ, a decrease in splenocyte proliferation and an increase in interleukin 10+ Foxp3- T cells in the spleen. CONCLUSION: Our results suggest that ATX-MS-1467 can induce splenic iTregs and long-term tolerance to MBP with the potential to partially reverse the pathology of multiple sclerosis, particularly during the early stages of the disease. FUNDING: EMD Serono, Inc., a business of Merck KGaA.

Pharmacophore-based design of novel oxadiazoles as selective sphingosine-1-phosphate (S1P) receptor agonists with in vivo efficacy.

Sphingosine-1-phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure-activity relationship exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five-membered heterocycles, and the use of diverse 2,2'-disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochemical properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds. From these optimization studies, a selective S1P1 agonist, N-methyl-N-(4-{5-[2-methyl-2'-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (45), and a dual S1P1,5 agonist, N-methyl-N-(3-{5-[2'-methyl-2-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (49), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head-to-head in an experimental autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan-S1P receptor agonist, S1P1,5 agonist 49 demonstrated comparable efficacy while S1P1 -selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.

[Construction and evaluation of educational software on urinary indwelling catheters]. / Construção e avaliação de software educacional sobre cateterismo urinário de demora.

Since this is an era in which information is open concerning the benefits it brings, the field of nursing informatics earns its moment. The objective of this study was to design educational software for teaching and learning the technique of urinary indwelling catheterization and compare the acquisition of knowledge regarding the technique before and after the implementation of the educational software. This is a descriptive study using a quantitative approach. The pedagogical foundations for designing the software were the theories of Piaget and Vygotsky. The teaching-learning process was evaluated through a questionnaire consisting of 10 multiple choice questions which the 60 participants completed before and after using the software. The results showed the software made significant contributions after its application, thus being very useful in the teaching-learning process.

EVALUATION OF THE RESULTS FROM REOPERATIONS ON PATIENTS WITH ROTATOR CUFF LESIONS.

OBJECTIVES: To assess the results from open or arthroscopic surgical treatment on patients with symptomatic recurrence of rotator cuff injuries. METHODS: Between December 1990 and July 2007, 30 patients were assessed and underwent reoperation performed by the Shoulder and Elbow Surgery Group of the Department of Orthopedics and Traumatology, Fernandinho Simonsen Wing, Santa Casa de São Paulo, because of dehiscence of the rotator cuff suture. The study included patients with symptomatic recurrence of the injury and with at least 24 months of postoperative follow-up. RESULTS: According to the UCLA evaluation criteria, 21 patients (70%) showed excellent or good outcomes; and nine patients (30%) showed fair or poor outcomes. CONCLUSION: Open or arthroscopic surgical treatment of recurrent rotator cuff injuries tended to present worse results than from the primary repair. In this study, we found that 70% of the results were excellent and good. The presence of extensive injuries in the reoperation tended to evolve with larger numbers of unsatisfactory results. In our study, we obtained better results from arthroscopic surgery than from open surgery.

EVALUATION OF THE RESULTS FROM ARTHROSCOPIC REPAIR ON ROTATOR CUFF INJURIES AMONG PATIENTS UNDER 50 YEARS OF AGE.

OBJECTIVE: To assess the results from arthroscopic surgical treatment of rotator cuff injuries among patients under 50 years of age. METHODS: Sixty-three patients with rotator cuff injuries who underwent arthroscopic surgical treatment performed by the Shoulder and Elbow Group of the Department of Orthopedics and Traumatology, in the Fernandinho Simonsen wing of Santa Casa Medical School, São Paulo, between August 1998 and December 2007, were reassessed. The study included all patients with rotator cuff injuries who were under 50 years of age and had been followed up postoperatively for at least 24 months. RESULTS: According to the UCLA evaluation criteria, 59 patients (92%) showed excellent and good results; five (8%) showed fair results; and none showed poor results. The postoperative evaluation showed that the mean range of motion was 145° for elevation, 47° for lateral rotation and T10 for medial rotation. Unsatisfactory results were associated with prolonged duration of the injury, with a statistically significant relationship. CONCLUSION: Arthroscopic repair of rotator cuff injuries in young patients produces excellent or good results for most patients.

The use of chemokine antagonists in EAE models.

Multiple sclerosis is believed to be an autoimmune disease with an end-point of neuro-degeneration, but in which inflammation plays a predominant role. Therefore therapies which target inhibition of the excessive recruitment of leukocytes into the central nervous system (CNS) are actively sought after by medical research. Drug discovery relies heavily on animal models used for such research, called Experimental Autoimmune Encephalomyelitis (EAE). Several chemokines and their receptors have been shown to play a role in this recruitment into the CNS, and we have investigated several strategies which antagonize this system in EAE models. We will discuss these strategies and their successes and failures to prevent disease symptoms and the insights they have provided.