Challenges of a two-phase orthodontic treatment of a mandibular lateral incisor-canine transposition and a maxillary palatally displaced canine: A case report.

INTRODUCTION: The management of eruption disturbances in orthodontics may be challenging and requires a careful diagnosis and treatment planning. This case report discusses the challenges of a two-phase orthodontic treatment of a patient presenting with a dental eruption pattern anomaly. PATIENT CONCERNS: A 10-year-old boy was presented with no complaints for a routine orthodontic evaluation during mixed dentition. PRIMARY DIAGNOSES: The patient was diagnosed with a skeletal Class I malocclusion with unilateral posterior crossbite, incomplete mandibular lateral incisor-canine transposition and a unilateral maxillary ectopic canine. INTERVENTIONS: Phase 1 started with rapid maxillary expansion to correct maxillary constriction and the ectopic eruption of the right maxillary canine. In the mandibular arch, phase 1 included the extraction of the left primary lateral incisor and canine, alignment of the left permanent lateral incisor and orthodontic traction of the left permanent canine. The duration of phase 1 was 14 months. Phase 2 involved a comprehensive course of orthodontic treatment and started when the patient was aged 13 years. This phase lasted 18 months. RESULTS: An adequate dental occlusion was obtained, and the treatment results were stable after an 18-month follow-up. CONCLUSION: In this case, the early diagnosis of the dental anomalies was valuable as it allowed an early intervention to be undertaken, which resulted in overall treatment simplification and potentially minimised the adverse effects. This case report reinforces the importance of a careful follow-up during mixed dentition.

Energetic responses of head-out water immersion at different temperatures during post-exercise recovery and its consequence on anaerobic mechanical power.

PURPOSE: While exercise recovery may be beneficial from a physiological point of view, it may be detrimental to subsequent anaerobic performance. To investigate the energetic responses of water immersion at different temperatures during post-exercise recovery and its consequences on subsequent anaerobic performance, a randomized and controlled crossover experimental design was performed with 21 trained cyclists. METHOD: Participants were assigned to receive three passive recovery strategies during 10 min after a Wingate Anaerobic Test (WAnT): control (CON: non-immersed condition), cold water immersion (CWI: 20 â„ƒ), and hot water immersion (HWI: 40 â„ƒ). Blood lactate, cardiorespiratory, and mechanical outcomes were measured during the WAnT and its recovery. Time constant (τ), asymptotic value, and area under the curve (AUC) were quantified for each physiologic parameter during recovery. After that, a second WAnT test and 10-min recovery were realized in the same session. RESULTS: Regardless the water immersion temperature, water immersion increased [Formula: see text] (+ 18%), asymptote ([Formula: see text]+ 16%, [Formula: see text] + 13%, [Formula: see text] + 17%, HR + 16%) and AUC ([Formula: see text]+ 27%, [Formula: see text] + 18%, [Formula: see text] + 20%, HR + 25%), while decreased [Formula: see text] (- 33%). There was no influence of water immersion on blood lactate parameters. HWI improved the mean power output during the second WAnT (2.2%), while the CWI decreased 2.4% (P < 0.01). CONCLUSION: Independent of temperature, water immersion enhanced aerobic energy recovery without modifying blood lactate recovery. However, subsequent anaerobic performance was increased only during HWI and decreased during CWI. Despite higher than in other studies, 20 °C effectively triggered physiological and performance responses. Water immersion-induced physiological changes did not predict subsequent anaerobic performance.

Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial.

BACKGROUND: Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19. METHODS: This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice daily for 10 days) or placebo (or other treatment groups not reported here). The trial team, site staff, and patients were masked to treatment allocation. Our primary outcome was a composite endpoint of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 up to 28 days post-random assignment on the basis of intention to treat. Modified intention to treat explored patients receiving at least 24 h of treatment before a primary outcome event and per-protocol analysis explored patients with a high level adherence (>80%). We used a Bayesian analytic framework to establish the effects along with probability of success of intervention compared with placebo. The trial is registered at ClinicalTrials.gov (NCT04727424) and is ongoing. FINDINGS: The study team screened 9803 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomisation to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. The average age of participants was 50 years (range 18-102 years); 58% were female. The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a teritary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756); relative risk [RR] 0·68; 95% Bayesian credible interval [95% BCI]: 0·52-0·88), with a probability of superiority of 99·8% surpassing the prespecified superiority threshold of 97·6% (risk difference 5·0%). Of the composite primary outcome events, 87% were hospitalisations. Findings for the primary outcome were similar for the modified intention-to-treat analysis (RR 0·69, 95% BCI 0·53-0·90) and larger in the per-protocol analysis (RR 0·34, 95% BCI, 0·21-0·54). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0·68, 95% CI: 0·36-1·27). There was one death in the fluvoxamine group and 12 in the placebo group for the per-protocol population (OR 0·09; 95% CI 0·01-0·47). We found no significant differences in number of treatment emergent adverse events among patients in the fluvoxamine and placebo groups. INTERPRETATION: Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital. FUNDING: FastGrants and The Rainwater Charitable Foundation. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Multidrug-Resistant (MDR) Klebsiella variicola Strains Isolated in a Brazilian Hospital Belong to New Clones.

Klebsiella variicola is mainly associated with opportunistic infections and frequently identified as Klebsiella pneumoniae. This misidentification implies a wrong epidemiology result as well as incorrect attribution to K. pneumoniae as the etiology of some severe infections. Recently, huge efforts have been made to study K. variicola, however, the biological aspects of this species are still unclear. Here we characterized five K. variicola strains initially identified as K. pneumoniae, with a Vitek-2 System and 16S rRNA sequencing. One-step multiplex polymerase chain reaction and Whole Genome Sequencing (WGS) identified them as K. variicola. Additionally, WGS analysis showed that all the strains are closely related with K. variicola genomes, forming a clustered group, apart from K. pneumoniae and K. quasipneumoniae. Multilocus sequence typing analysis showed four different sequence types (STs) among the strains and for two of them (Kv97 and Kv104) the same ST was assigned. All strains were multidrug-resistant (MDR) and three showed virulence phenotypes including invasion capacity to epithelial cells, and survival in human blood and serum. These results showed the emergence of new K. variicola clones with pathogenic potential to colonize and cause infection in different tissues. These characteristics associated with MDR strains raise great concern for human health.

Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. Objective: To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and Participants: This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. Interventions: Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and Measures: The primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. Results: Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance: In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19-associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04403100.

Nutritional recovery with a soybean diet impaired the glucagon response but did not alter liver gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation.

Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 µU/mg vs. control groups, 3.6 ± 0.6 µU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.

In vitro efficacy of essential oils and extracts of Schinus molle L. against Ctenocephalides felis felis.

Extracts and essential oils from plants are important natural sources of pesticides. These compounds are considered an alternative to control ectoparasites of veterinary importance. Schinus molle, an endemic species of Brazil, produces a high level of essential oil and several other compounds. The aim of this work was to determinate the chemical composition of extracts and essential oils of S. molle and further to evaluate the activity against eggs and adults of Ctenocephalides felis felis, a predominant flea that infests dogs and cats in Brazil. In an in vitro assay, the non-polar (n-hexane) extract showed 100% efficacy (800 µg cm(-2); LD50 = 524·80 µg cm(-2)) at 24 and 48 h. Its major compound was lupenone (50·25%). Essential oils from fruits and leaves were evaluated, and had 100% efficacy against adult fleas at 800 µg cm(-2) (LD50 = 353·95 µg cm(-2)) and at 50 µg cm(-2) (LD50 = 12·02 µg cm(-2)), respectively. On the other hand, the essential oil from fruits and leaves was not active against flea eggs. This is the first study that reports the insecticidal effects of essential oils and extracts obtained from Schinus molle against Ctenocephalides felis felis.

Basal cell nevus syndrome: clinical and molecular review and case report.

Basal cell nevus syndrome (BCNS), also referred to as nevoid basal cell carcinoma syndrome or Gorlin-Goltz syndrome, was first described by Gorlin and Goltz in 1960 as an autosomal dominant disorder characterized by the early appearance of multiple basal cell carcinomas (BCCs), keratocysts of the jaw, ectopic calcifications, palmar and plantar pits, and anomalies of the ocular, skeletal, and reproductive systems. The genesis of this cancer's etiology in relation to BCNS was unclear until a few years ago when molecular analysis studies suggested a relationship between BCC and the loss-of-function mutations of the patched gene (PTCH) found on chromosome arm 9q. PTCH inhibits signaling by the membrane protein Smoothened (Smo), and this inhibition is relieved by binding sonic hedgehog (SHH) to PTCH. We describe a patient with multiple BCCs associated with x-ray anomalies of BCNS and review the basis of the SHH signaling pathway and clinical aspects of BCNS.

Comparative evaluation of calcium hypochlorite and sodium hypochlorite associated with passive ultrasonic irrigation on antimicrobial activity of a root canal system infected with Enterococcus faecalis: an in vitro study.

INTRODUCTION: The purpose of this study was to compare in vitro the effectiveness of calcium hypochlorite (Ca[OCl]2) and sodium hypochlorite (NaOCl) associated with passive ultrasonic irrigation in root canals of bovine teeth infected with Enterococcus faecalis. METHODS: The root canals of 60 single-rooted bovine extracted teeth were enlarged up to a file 45, autoclaved, inoculated with Enterococcus faecalis, and incubated for 30 days. The samples were divided into 6 groups (n = 10) according to the protocol for decontamination: G1: no treatment; G2: distilled water; G3: 2.5% NaOCl; G4: 2.5% Ca(OCl)2; G5: 2.5% NaOCl with ultrasonic activation; and G6: 2.5% Ca(OCl)2 with ultrasonic activation (US). Microbiological testing (colony-forming unit [CFU] counting) was performed to evaluate and show, respectively, the effectiveness of the proposed treatments. Data were subjected to 1-way analysis of variance followed by the post hoc Tukey test (α = 0.05). RESULTS: Groups 1 and 2 showed the highest mean contamination (3.26 log10 CFU/mL and 2.69 log10 CFU/mL, respectively), which was statistically different from all other groups (P < .05). Group 6 (Ca[OCl]2 + US) showed the lowest mean contamination (1.00 log10 CFU/mL), with no statistically significant difference found in groups 3 (NaOCl), 4 (Ca[OCl]2), and 5 (NaOCl + US) (P < .05). CONCLUSIONS: Ca(OCl)2 as well as passive ultrasonic irrigation can aid in chemomechanical preparation, contributing in a significant way to the reduction of microbial content during root canal treatment.

Nutritional recovery promotes hypothalamic inflammation in rats during adulthood.

We evaluated whether protein restriction in fetal life alters food intake and glucose homeostasis in adulthood by interfering with insulin signal transduction through proinflammatory mechanisms in the hypothalamus and peripheral tissues. Rats were divided into the following: a control group (C); a recovered group (R); and a low protein (LP) group. Relative food intake was greater and serum leptin was diminished in LP and R compared to C rats. Proinflammatory genes and POMC mRNA were upregulated in the hypothalamus of R group. Hypothalamic NPY mRNA expression was greater but AKT phosphorylation was diminished in the LP than in the C rats. In muscle, AKT phosphorylation was higher in restricted than in control animals. The HOMA-IR was decreased in R and C compared to the LP group. In contrast, the K(itt) in R was similar to that in C and both were lower than LP rats. Thus, nutritional recovery did not alter glucose homeostasis but produced middle hyperphagia, possibly due to increased anorexigenic neuropeptide expression that counteracted the hypothalamic inflammatory process. In long term protein deprived rats, hyperphagia most likely resulted from increased orexigenic neuropeptide expression, and glucose homeostasis was maintained, at least in part, at the expense of increased muscle insulin sensitivity.

Nutritional recovery with okara diet prevented hypercholesterolemia, hepatic steatosis and glucose intolerance.

We assessed the biological value of an okara diet and its effects on the hormonal and metabolic profile of rats submitted to protein restriction during intra-uterine life and lactation and recovered after weaning. Male rats from mothers fed either 17% or 6% protein during pregnancy and lactation were maintained on 17% casein (CC, LC), 17% okara (CO, LO) or 6% casein (LL) diets over 60 d. The nutritional quality of the okara protein was similar to that of casein. The okara diet was effective in the nutritional recovery of rats in growing that were malnourished in early life. Furthermore, the okara diet reversed the hypercholesterolemia and the hepatic steatosis observed in the malnutrition and prevented glucose intolerance in an animal model prone to diabetes mellitus.

Phenolic chemical composition of Petroselinum crispum extract and its effect on haemostasis.

From the aqueous extract (Pc) of Petroselinum crispum (Mill) flat leaves specimens were isolated and identified the flavonoids apigenin (1), apigenin-7-O-glucoside or cosmosiin (2), apigenin-7-O-apiosyl-(1 --> 2)-O-glucoside or apiin (3) and the coumarin 2",3"-dihydroxyfuranocoumarin or oxypeucedanin hydrate (4). The inhibitory activity toward clotting formation and platelet aggregation was assessed for Pc flavonoids (1) and (2), and the coumarin (4). Pc showed no inhibition on clotting activity when compared with the control. On the other hand, a strong antiplatelet aggregation activity was observed for Pc (IC50 = 1.81 mg/mL), apigenin (IC50 = 0.036 mg/mL) and cosmosiin (IC50 = 0.18 mg/mL). In all cases ADP was used as inductor of platelet aggregation. Our results showed that Pc, apigenin and cosmosiin interfere on haemostasis inhibiting platelet aggregation. To the best of our knowledge this is the first report for the cosmosiin antiplatelet aggregation in vitro activity.

Analysis of muscle activation during different leg press exercises at submaximum effort levels.

Many studies have analyzed muscle activity during different strength exercises. Although the leg press (LP) is one of the most common exercises performed, there is little evidence of lower limb muscle activity patterns during this exercise and its variations. Thus, this study aimed to verify how mechanical changes and loads affect lower limb muscle activity during the performance of different LP exercises. Fourteen women performed 3 LP exercises: 45 degrees LP (LP45), LP high (LPH), and LP low (LPL) at 40% and 80% of the 1 repetition maximum. The electromyographic activity of the rectus femoris, vastus lateralis, biceps femoris, gastrocnemius, and gluteus maximus was recorded. Results suggested that mechanical changes affect lower limb muscle activity and that it is related to the load used. At moderate effort levels, the rectus femoris and gastrocnemius were more active during the LP45 and LPL than during the LPH. At a high effort level, the rectus femoris and vastus lateralis (quadriceps) were more active during the LPL than the LPH. Again, the rectus femoris and gastrocnemius were more active during the LP45 and LPL than the LPH. On the other hand, gluteus maximus activity was greater during the LPH than the LPL. This study found that coordination patterns of muscle activity are different when performing LP variations at high or moderate effort levels because of mechanical changes and different loads lifted during the different LP exercises. These results suggest that if the goal is to induce greater rectus femoris and vastus lateralis (quadriceps) activation, the LPL should be performed. On the other hand, if the goal is to induce gluteus maximus activity, the LPH should be performed.

Sarna costrosa en un lactante desnutrido / Crusted scabies in a malnourished infant

La sarna costrosa o sarna noruega es una forma de escabiosis altamente contagiosa, debido al gran número de parásitos en la piel, como resultado de una falla de la respuesta inmune del huésped. A diferencia de la forma clásica, el prurito es menos intenso y las pápulas eritematosas, así como los túneles escabióticos pueden estar en pequeño número o ausentes. En los casos generalizados puede haber desarrollo de linfadenopatía e infección secundaria con evolución a sepsis u otra complicación grave. Reportamos el caso de un lactante de cinco meses de edad, desnutrido, con cuadro de sarna costrosa asociado a alteraciones significativas en los exámenes físico y de laboratorio (AU)

The crosted or norwegian scabies is a highly contagious form of scabies, given great number of parasites in the skin, resultant of an imperfection of the immune deffense of the host. In this clinic presentation, pruritus is less intense and eritematous papules as well as linear burrows can occur in small number or exactly absent. In generalized cases it can have the development of adenopathy and secondary infection can occur being able to evolve for sepse or serious other complications.We report the case of an infant of 5 months of age, malnourished, with crosted scabies associated with significative alterations in the physical and laboratorial examinations (AU)

Kalanchosine dimalate, an anti-inflammatory salt from Kalanchoe brasiliensis.

This report describes the isolation and characterization of kalanchosine dimalate (KMC), an anti-inflammatory salt from the fresh juice of the aerial parts of Kalanchoe brasiliensis. KMC comprises the new metabolite kalanchosine (1) and malic acid (2) in a 1:2 stoichiometric ratio. Kalanchosine (1), 3,6-diamino-4,5-dihydroxyoctanedioic acid, is the first naturally occurring dimeric bis(gamma-hydroxy-beta-amino acid) and is at least partially responsible for the anti-inflammatory properties of K. brasiliensis.

Quercitrin: an antileishmanial flavonoid glycoside from Kalanchoe pinnata.

Quercitrin (quercetin 3- O-alpha- L-rhamnopyranoside), one of the constituents of the biologically active aqueous extract obtained from Kalanchoe pinnata, is demonstrated to be a potent antileishmanial compound (IC50 approximately 1 microg/mL) with a low toxicity profile. This is the first time that antileishmanial activity is demonstrated for a flavonoid glycoside.

First isolation of a symmetrical glycosylated methylene bisflavonoid.

Blutaparon portulacoides (St. Hil.) Mears (= Philoxerus portulacoides St. Hil.) (Amaranthaceae) is a species occurring in the Brazilian coast in two botanical varieties. The chemical study of an ethanolic extract led to the isolation of spinacetin 3- O-robinobioside as well as an unique glycosylated pseudo-dimeric flavonoid identified as 8,8""-methylene bis(spinacetin 3- O-robinobioside) mainly by NMR analyses (1H, 1H- 1H COSY, 13C, HMQC, HMBC) and MALDI-TOF mass spectrometry.