Ischemic-Trained Monocytes Improve Arteriogenesis in a Mouse Model of Hindlimb Ischemia.

OBJECTIVE: Monocytes, which play an important role in arteriogenesis, can build immunologic memory by a functional reprogramming that modifies their response to a second challenge. This process, called trained immunity, is evoked by insults that shift monocyte metabolism, increasing HIF (hypoxia-inducible factor)-1α levels. Since ischemia enhances HIF-1α, we evaluate whether ischemia can lead to a functional reprogramming of monocytes, which would contribute to arteriogenesis after hindlimb ischemia. METHODS AND RESULTS: Mice exposed to ischemia by 24 hours (24h) of femoral artery occlusion (24h trained) or sham were subjected to hindlimb ischemia one week later; the 24h trained mice showed significant improvement in blood flow recovery and arteriogenesis after hindlimb ischemia. Adoptive transfer using bone marrow-derived monocytes (BM-Mono) from 24h trained or sham donor mice, demonstrated that recipients subjected to hindlimb ischemia who received 24h ischemic-trained monocytes had remarkable blood flow recovery and arteriogenesis. Further, ischemic-trained BM-Mono had increased HIF-1α and GLUT-1 (glucose transporter-1) gene expression during femoral artery occlusion. Circulating cytokines and GLUT-1 were also upregulated during femoral artery occlusion.Transcriptomic analysis and confirmatory qPCR performed in 24h trained and sham BM-Mono revealed that among the 15 top differentially expressed genes, 4 were involved in lipid metabolism in the ischemic-trained monocytes. Lipidomic analysis confirmed that ischemia training altered the cholesterol metabolism of these monocytes. Further, several histone-modifying epigenetic enzymes measured by qPCR were altered in mouse BM-Mono exposed to 24h hypoxia. CONCLUSIONS: Ischemia training in BM-Mono leads to a unique gene profile and improves blood flow and arteriogenesis after hindlimb ischemia.

Material Identification on Thin Shells Using the Virtual Fields Method, Demonstrated on the Human Eardrum.

Characterization of material parameters from experimental data remains challenging, especially on biological structures. One of such techniques allowing for the inverse determination of material parameters from measurement data is the virtual fields method (VFM). However, application of the VFM on general structures of complicated shape has not yet been extensively investigated. In this paper, we extend the framework of the VFM method to thin curved solids in three-dimensional, commonly denoted shells. Our method is then used to estimate the Young's modulus and hysteretic damping of the human eardrum. By utilizing Kirchhoff plate theory, we assume that the behavior of the shell varies linearly through the thickness. The total strain of the shell can then be separated in a bending and membrane strain. This in turn allowed for an application of the VFM based only on data of the outer surface of the shell. We validated our method on simulated and experimental data of a human eardrum made to vibrate at certain frequencies. It was shown that the identified material properties were accurately determined based only on data from the outer surface and are in agreement with literature. Additionally, we observed that neither the bending nor the membrane strain in an human eardrum can be neglected and both contribute significantly to the total strain found experimentally.

Elucidating the Splitting Behavior of Tablets to Optimize the Pharmacotherapy in Veterinary Medicine.

It is well known that the splitting of tablets can bring serious risks to the health of the treated animals, e.g., the possible adverse reactions caused by overdoses of fenbendazole or aspirin. In this regard, this work aimed to evaluate, for the first time, the splitting behavior of commercial veterinary tablets and identifying the technological aspects that interfere in this process. Tablets were cut in halves using a tablet splitter and were analyzed regarding mass variation, mass loss, friability, and hardness. Microstructural and morphological evaluations were also performed. For most of the tablets, organic flavor additives provided more uniformity and cohesive matrix, which preserved its hardness after the cut and led to subdivision results within acceptable limits for mass measurements and friability. Apart from the microstructure, the most critical technological aspect for a correct splitting performance in such tablets was the presence of a score. Thus, the results presented here allow us to guide the manufacturing of veterinary drug products in order to produce tablets more adapted to the splitting process.

Does induced current density explain the C-H and C-F Perlin effects?

Spin-spin coupling constant (SSCC) data may be useful in providing information on the stereochemistry and intramolecular interactions in molecules. One-bond C-H and C-F SSCCs (1JCH and 1JCF) are amongst the most important NMR parameters used to study the structure of alicyclic six-membered rings, because the Perlin effect, defined as 1JCHeq > 1JCHax, and the fluorine Perlin-like effect, defined as |1JCFeq| > |1JCFax|, are in wide currency to probe the conformations of these compounds. The origin of these effects has been usually attributed either to dipolar interactions or hyperconjugation, while the induced current density (ICD) has been recently correlated to the magnetic shielding tensors in some six-membered ring compounds, and then used to explain the Perlin effect. Accordingly, this work reports an analysis of the ICD as a descriptor of 1JCH and 1JCF in a series of six-membered rings to find out the role of the ICD in the conventional and fluorine Perlin effect. The atoms in molecules (AIM) magnetic responses obtained from density functional theory (DFT) calculations for the studied compounds did not show any relationship of the first-order electronic current density (ΔJ(1)) with the calculated Δ1JCHax-eq and Δ1JCFax-eq values. Consequently, the title effects cannot be precisely explained by ICD. Nevertheless, an interesting relationship between ΔJ(1) and Δdelocalization involving σCH* orbitals is observed.

Structural intensity assessment on shells via a finite element approximation.

Structural intensity on plates or shells can provide insights on how the vibrational energy is transmitted throughout a sample. Its assessment via experimental deflections are widely documented in the case of plates, which just requires the computation of spatial derivatives of out-of-plane displacements or velocities and a knowledge of the sample's material properties. However, if the structural intensity is to be assessed on arbitrary shells, a more elaborate data processing is required. The in-plane displacements become relevant terms and the spatial derivatives along a predefined local coordinate system need to be computed. Here, a method from which experimental data is interpolated on a finite element mesh is proposed. First, the global displacements and shape of a sample's outer-surface are measured. These data are then projected on a quadratic mesh, where the Kirchhoff plate theory is invoked for the individual elements. The data differentiation is computed via quadratic shape functions, from which the strains and structural intensity are estimated. Through the obtained vibrational energy results on the basis of measured displacement and shape data and by validating the method via a numerical simulation, the proposed work has shown to be a reliable tool to assess energy transmission on irregular shells.

Congenital persistent infection with bovine viral diarrhea virus not observed in piglets.

This study was designed to determine whether congenital persistent infection occurs in piglets from gilts experimentally inoculated with bovine viral diarrhea virus type 2 (BVDV-2). Six pregnant gilts were divided into 2 groups, infected (n = 4), and control (n = 2). The gilts were inoculated at 45 days gestation. Piglets were assessed for 35 days following birth with nasal swab and blood sample collections every 72 hours. Reverse transcriptase-polymerase chain reaction (RT-PCR) tests were performed for direct diagnosis of virus in blood and nasal swabs, and virus neutralization was used for antibody detection. Transplacental transmission of BVDV-2 did not occur. Piglets were born free of the virus and did not shed BVDV during the experimental period.

Infection congénitale persistante par le virus de la diarrhée virale bovine non observée chez les porcelets. Cette étude a évalué l'occurrence d'infection congénitale persistante chez des porcelets nés de cochettes inoculées expérimentalement avec le virus BVDV-2. Six cochettes gestantes ont été divisées en deux groupes, infectées (n = 4) et témoins (n = 2). L'inoculation a eu lieu à 45 jours de gestation. Les porcelets ont été évalués pendant 35 jours par prélèvement d'écouvillons nasaux et d'échantillons de sang toutes les 72 heures. Des tests d'amplification en chaîne par la polymérase avec la transcriptase réverse (RT-PCR) ont été effectués pour le diagnostic direct dans le sang et les écouvillons, et la neutralisation virale pour l'évaluation sérologique. La transmission transplacentaire de BVDV-2 n'a pas été mise en évidence car les porcelets sont nés sans virus et n'ont pas éliminé le BVDV au cours de la période expérimentale.(Traduit par les auteurs).

IgA Vasculitis Followed by IgA Nephropathy Without an Identifiable Trigger: The Same Disease or a Spectrum of Related Conditions?

IgA vasculitis and IgA nephropathy are characterized by IgA deposition in blood vessels and glomerular mesangium, respectively. The former is far more common in the pediatric population, while the latter presents more often in adulthood. A consensus regarding whether these two conditions are manifestations of the same disease that occurs on a spectrum has not yet been reached, and, to our knowledge, no clinical trials to address this question have been conducted. Here, we describe a 27-year-old patient who presented to the emergency department multiple times before being diagnosed with IgA vasculitis with no identifiable trigger and soon after developed IgA nephropathy. This case highlights the importance of ruling out these conditions, especially IgA vasculitis, in adults presenting with a petechial rash, but also the need for studies that investigate whether and how these conditions are related so that patients can be appropriately diagnosed and treated as efficiently as possible.

A Rare Case of Pertuzumab-Induced Toxic Epidermal Necrolysis.

Pertuzumab is a targeted therapy drug that is employed in the management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and works by blocking the ability of cancer cells to receive growth and proliferation signals. Toxic epidermal necrolysis (TEN) is a severe cutaneous manifestation characterized by widespread erythema, necrosis, and bullous detachment of the skin involving more than 10% of the body surface area (BSA) and may be precipitated by an immunologic response to the administration of certain medications. However, TEN development as a consequence of HER2 inhibitor therapy has not been described in the existing literature. A 44-year-old female with a history of metastatic breast cancer to the liver presented with a diffuse blistering rash following a first-time administration of pertuzumab three days prior. Her rash began as painful and pruritic blisters 12 hours after the last infusion of pertuzumab and progressed to involve her arms, chest, groin, and thighs with a positive Nikolsky sign. She was managed supportively with high-dose steroids and antihistamines, and although her hospital course was complicated by hypotension requiring pressor support, she gradually made a full recovery and was released to a rehabilitation facility.

In-situ formation of nanoparticles from drug-loaded 3D polymeric matrices.

The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with oral drug bioavailability. Such polymeric pharmaceuticals are becoming increasingly common on the market and can become even more popular due to the dizzying advance of 3D printing medicines. Hence, this work aimed to study this phenomenon during the dissolution of 3D printed tablets produced with three different polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and Eudragit RL PO® (EUD RL) combined with plasticizers and the model drug naringenin (NAR). The components' interaction, dissolution behavior, and characteristics of the formed particles were investigated employing thermal, spectroscopic, mechanical, and chromatographic assays. All the systems generated stable spherical-shaped particles throughout 24 h, encapsulating over 25% of NAR. Results suggest encapsulation efficiencies variations may depend on interactions between polymer-drug, drug-plasticizer, and polymer-plasticizer, which formed stable nanoparticles even in the drug absence, as observed with the HPMCAS and EUD RL formulations. Additionally, components solubility in the medium and previous formulation treatments are also a decisive factor for nanoparticle formation. In particular, the treatment provided by hot-melt extrusion and FDM 3D printing affected the dissolution efficiency enhancing the interaction between the components, reverberating on particle size and particle formation kinetics mainly for HPMCAS and EUD RL. In conclusion, the 3D printing process influences the in-situ formation of nanoparticles, which can directly affect oral drug bioavailability and needs to be monitored.

Postinfarction Ventricular Septal Ruptures During the COVID-19 Pandemic: Two Case Series.

This case series highlights the occurrence of hemodynamically significant ventricular septal defects (VSDs) in two patients presenting with ST-elevation myocardial infarction (STEMI) during the COVID-19 pandemic. This paper aims to emphasize the delayed presentation of cardiac emergencies, such as STEMI, due to concerns about contracting COVID-19. This delay has led to an increased risk of rare complications, including VSD, associated with STEMI. The first case involves a 92-year-old male with a history of hypertension, hyperlipidemia, chronic kidney disease, and coronary artery disease. He presented with acute chest pain, and diagnostic tests revealed ST elevations and a VSD. Despite intervention efforts, including hemodynamic support, the patient's condition deteriorated, and he passed away due to advanced age and high surgical risk. The second case involves a 62-year-old female with a medical history of diabetes, hypertension, and hyperlipidemia. She presented with left-sided chest pain, and an angiogram revealed a mid-right coronary artery stenosis and a thrombus. During the procedure, the patient experienced hypotension, requiring hemodynamic support. Subsequent evaluations identified a large VSD with right ventricular dysfunction. The patient underwent a series of interventions, including a ventricular assist device and VSD closure, but experienced multi-organ failure and ultimately passed away. VSDs following acute myocardial infarction (MI) are rare but life-threatening complications. Early revascularization is crucial in preventing the development of VSDs. These cases demonstrate the importance of prompt diagnosis and intervention, as delayed presentation increases the risk of mechanical complications. Surgical closure remains the definitive treatment for postinfarction VSDs.

Agranulocytosis Secondary to Cancer Chemotherapy Associated With Higher In-Hospital Mortality in Patients With Central Line Insertion During a Hospital Stay.

Background Agranulocytosis secondary to cancer chemotherapy (ASCC) remains a leading cause of morbidity and mortality. Central line-associated bloodstream infections (CLABSI) are also particularly prevalent in these populations and may portend a poorer outcome. Our study serves to investigate the relationship between patients with agranulocytosis secondary to cancer chemotherapy and the insertion of a central venous catheter (CVC) with respect to in-hospital mortality. Methods and results We utilized the National Inpatient Survey 2019 database. We utilized the International Classification of Diseases (ICD)-10 CM codes to identify ASCC and other medical comorbidities. We utilized ICD-10 PCS codes to identify CVC insertions. Multivariate logistic regression was utilized to study the effect of CVC insertion on in-hospital mortality. In patients with ASCC, CVC insertion was associated with a higher in-hospital mortality (unadjusted: 11.9% vs. 1%, p<0.001, adjusted OR 19.27, 95% CI 5.84 - 65.6, p<0.001) adjusted for baseline characteristics and other comorbidities. Patients in the study cohort who were older than 70 years of age also had a higher in-hospital mortality relative to younger age groups (adjusted OR 2.31, 95% CI 1.04-5.13, p<0.039). Conclusion In patients with ASCC, CVC insertion during hospitalization is associated with higher in-hospital mortality.

A review of treatment options employed in relapsed/refractory AML.

INTRODUCTION: Acute myeloid leukemia [AML] is a heterogenous group of primary hematopoietic neoplasms arising from myeloid precursor cells. Up to 50% of patients failed to achieve remission with initial therapy and go on to develop refractory AML. Whenever possible, enrollment in a clinical trial in view of the paucity of evidence surrounding a clearly superior treatment modality is recommended, and the therapy which provides the best chance for cure post remission is allogeneic hematopoietic stem cell transplantation [HCT], with much of everyday clinical decision-making in relapsed/refractory (R/R) AML surrounding the choice of the least toxic regimen that could achieve remission and enable prompt HCT. DISCUSSION: We discuss a variety of treatment modalities employed in the R/R AML setting beginning with traditional cytotoxic regimens. We then turn our attention to targeted therapies that have shown efficacy in specific patient populations such as the IDH inhibitors and FLT3 inhibitors and lastly, we turn our attention to immunotherapeutic agents employed in the R/R in the setting, such as CD33 inhibitors and bispecific antibodies. CONCLUSION: It appears increasingly clear that approaching AML as a homogenous disease entity is unsatisfactory in view of the variations in such disease factors as cytogenetic and molecular markers, age, and disease severity at presentation; all of which contribute significantly to heterogeneity of the disease. Moving forward, treating AML would likely require tailored therapy following advances in technology such as molecular profiling, drug sensitivity and resistance testing.

Diagnostic dilemma in a patient presenting with thrombotic microangiopathy in the setting of pregnancy.

We report a case of thrombotic microangiopathy in a postpartum female for which considerable diagnostic uncertainty existed initially regarding the etiology. This case highlights the limitations surrounding PLASMIC scoring criteria for the diagnosis of thrombotic thrombocytopenic purpura (TTP). A 32-year-old woman presented to maternofetal medicine in her third trimester of pregnancy at 32 weeks for a routine follow up and was subsequently found to have elevated blood pressures with proteinuria, and was diagnosed with pre-eclampsia. Worsening anemia and thrombocytopenia prompted a blood smear which showed schistocytes, concerning for a thrombotic microangiopathy. Creatinine was also elevated with normal liver enzymes being noted. A PLASMIC score of 4 placed her in the low-risk category for severe ADAMTS13 deficiency whilst she fulfilled criteria for partial HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome per Tennessee classification. Despite delivery, her symptoms persisted with subsequent ADAMTS13 assay confirming acquired TTP, subsequently requiring repeated plasmapheresis and rituximab to achieve disease control. Thrombotic microangiopathy remains a diagnostic challenge especially in the peripartum population, and scoring systems such as PLASMIC score and Tennessee classification may be of limited utility.

Nanostructured lipid carriers loaded with an association of minoxidil and latanoprost for targeted topical therapy of alopecia.

Alopecia is a condition associated with different etiologies, ranging from hormonal changes to chemotherapy, that affects over 80 million people in the USA. Nevertheless, there are currently few FDA-approved drugs for topical treatment, and existing formulations still present skin irritation issues, compromising treatment adherence. This work aimed to develop a safe formulation based on nanostructured lipid carriers (NLC) that entrap an association of minoxidil and latanoprost and target drug delivery to the hair follicles. To do so, thermal techniques combined with FTIR were used to assess the chemical compatibility of the proposed drug association. Then, NLC with 393.5 ± 36.0 nm (PdI < 0.4) and +22.5 ± 0.2 mV zeta potential were produced and shown to entrap 86.9% of minoxidil and 99.9% of latanoprost efficiently. In vitro, the free drug combination was indicated to exert positive effects over human primary epidermal keratinocytes, supporting cell proliferation, migration and inducing the mRNA expression of MKI67 proliferation marker and VEGF - a possible effector for minoxidil-mediated hair growth. Interestingly, such a favorable drug combination profile was optimized when delivered using our NLC. Furthermore, according to the HET-CAM and reconstructed human epidermis assays, the nanoformulation was well tolerated. Finally, drug penetration was evaluated in vitro using porcine skin. Such experiments indicated that the NLC could be deposited preferentially into the hair follicles, causing a considerable increase in the penetration of the two drugs in such structures, compared to the control (composed of the free compounds) and generating a target-effect of approximately 50% for both drugs. In summary, present results suggest that hair follicle-targeted delivery of the minoxidil and latanoprost combination is a promising alternative to treat alopecia.

A Rare Case of Pseudomembrane-Associated Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic, life-long inflammatory bowel disease that normally presents with bloody diarrhea, fever, abdominal pain, and leukocytosis. Diagnosis is usually based on clinical presentation, endoscopy with biopsy, and exclusion of alternative diagnoses. In very rare cases, pseudomembranes may be found on colonoscopy in patients with an early UC flare. Historically, the objective finding of pseudomembranes has been exclusively used to diagnose a Clostridioides difficile infection (CDI); however, diagnostic testing must be correctly utilized to confirm whether a CDI is truly the cause of the presence of pseudomembranes, and not an alternative etiology, such as UC. In this case, we discuss a 43-year-old female who presented to the hospital with worsening chronic bloody diarrhea after being seen in the outpatient clinic for a questionable CDI. She underwent endoscopic evaluation revealing pseudomembranous colitis; however, C. difficile testing showed one positive gastrointestinal (GI) pathogen panel and multiple negative antigens and toxin enzyme immunoassays (EIA). With a clinical suspicion of early UC, the patient was treated with mesalamine enemas and improved clinically before discharge. Several months later, she underwent endoscopic evaluation with biopsy, which showed findings consistent with a diagnosis of UC.

Nanostructured lipid carriers for hair follicle-targeted delivery of clindamycin and rifampicin to hidradenitis suppurativa treatment.

Hidradenitis suppurativa is a chronic and debilitating inflammatory condition related to a permanent obstruction of the pilosebaceous units. Until nowadays, therapeutic options are unsatisfactory. Here, we propose nanostructured lipid carriers (NLC) entrapping an association of clindamycin phosphate (CDM) and rifampicin (RIF) as a topical alternative for the treatment of the disease. Chemical compatibility between the drugs was demonstrated using thermal analysis combined with ATR-FTIR and X-ray powder diffraction assays. Nanocarriers' diameter was narrowly distributed (polydispersity index = 0.2) around 400 ± 14 nm, they possess a negative surface charge (-48.9 ± 0.7 mV) and high drug entrapment efficiencies (80.2 ± 0.4 % and 93.4 ± 0.7 % for CDM and RIF, respectively). The formulation proved to be safe for the topical application, as it was non-irritant on both HET-CAM and reconstructed human epidermis (RHE) assays. Spin-label EPR indicated an NLC affinity for the lipidic domains of stratum corneum, which could benefit the targeting of the sebaceous units. Indeed, when applied on the skin in vitro, even when mimicking the sebaceous condition, NLC accumulated into the hair follicles openings, not altering the amount of accumulated CDM and significantly increasing by 12-fold the uptake of RIF in these structures. In conclusion, developed NLC formulation incorporating the antibiotics CDM and RIF is a promising strategy for the topical treatment of hidradenitis suppurativa or other infections that may affect the pilosebaceous units.

Predictive models of FDM 3D printing using experimental design based on pharmaceutical requirements for tablet production.

The present study aimed to analyze how the printing process affects the final state of a printed pharmaceutical product and to establish prediction models for post-printing characteristics according to basic printing settings. To do this, a database was constructed through analysis of products elaborated with a distinct printing framework. The polymers acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and high-impact polystyrene (HIPS) were tested in a statistically-based experiment to define the most critical printing factors for mass, mass variation, printing time, and porosity. Then, a predictive model equation was established and challenged to determine two different medical prescriptions. The factors of size scale, printlet format, and print temperature influenced printlet mass, while the printing time was impacted by size scale, printing speed, and layer height. Finally, increased printing speed leads to more porous printlets. The prescript-printed tablets showed average mass, mass variations, and porosity close to theoretical values for all filaments, which supports the adequacy of the optimized design of experiments for tablet production. Hence, printing settings can be preselected according to the desired product's characteristics, resulting in tablets produced with higher precision than usually achieved by compounding pharmacies.

Lipid nanoparticles as carriers of cyclodextrin inclusion complexes: A promising approach for cutaneous delivery of a volatile essential oil.

Solid inclusion complexes with cyclodextrins (CD) may be used to overcome volatility and solubility problems of essential oils of pharmacological interest. However, they lack the many dermatological advantages of lipid nanoparticles. This study intends to evaluate the ability of nanostructured lipid carriers (NLC) to encapsulate hydroxypropyl-ß-cyclodextrin inclusion complexes of Lippia origanoides essential oil (EO) and to maintain the desirable aspects of lipid colloids interaction with the skin, specifically follicular accumulation and controlled delivery. CD and NLC were also evaluated separately. Thymol (TML) was used as the essential oil marker and to produce control formulations. As expected, CD alone, though effective in overcoming volatility and low aqueous solubility of TML, were ineffective in controlling marker release (˜50% of EO released after 3 h, Hixson-Crowell kinetics). Even though NLC controlled drug release (˜20% EO released after 12 h, zero-order kinetics) enabling TML penetration into the skin (> 40 µg/cm2after 12 h), NLC alone were not efficient in preventing TML volatility, especially at higher temperatures (calculated shelf-life of 2 days at 35 °C). The combined approach resulted in a synergistic effect (˜20% EO released after 12 h; shelf life of 6 days). The lack of statistical difference of TML skin penetration from NLC and NLC-CD suggests the developed system maintained all skin interaction aspects of lipid colloids, including follicular accumulation forming a depot for controlled delivery. In conclusion, lipid nanoparticles demonstrated to be promising carriers for inclusion complexes of this particular volatile essential oil.

Evaluation of the chemical, sensory and volatile composition of sapota-do-Solimões pulp at different ripening stages.

The aim of this study was to evaluate sapota-do-Solimões (Quararibea cordata Vischer) during ripening, verifying physical, chemical and sensory parameters, bioactive and volatile compounds. The pulps were obtained from fruits from the city of Tefé, AM, Brazil and collected at three different ripening stages: unripe (U); ripe collected from the tree (R); and ripe collected from the ground (RG). The biometric and quality parameters, total carotenoids, total phenolic compounds, chemical composition, fatty acids and volatile profiles were analyzed. The sapota-do-Solimões fruits showed positive correlation with evolution of ripened stage of the variables water activity (0.977-0.996), pH (6.53-7.04), soluble solids (8.53-12.65%), total sugars (4.26-7.98%), reducing sugars (0.99-3.14%), non-reducing sugars (3.11-4.60%) and total carotenoids (0.67-1.24 µg/g). Longitudinal and transversal diameters and fruit mass were higher in RG compared with the other ripening stages. The lipids contents increased from 0.16% for U to 0.30% for RG. The palmitic (47.1-86.4), stearic (3.1-5.9), oleic (44.4-131.1) and vaccenic (25.3-37.7) increased while palmitoleic (16.4-10.0) and linoleic (6.6-3.5) decreased. A total of 86 volatile compounds were identified, of which 57 were found in U fruits, 54 in R fruits and 68 in RG fruits. The classes most relevant found were alcohols, aldehydes, esters, ketones, furans and terpenes. An increase in the terpenes (0.4-5.6%) from U fruit to RG fruit showed potentials odoriferous characteristics, as well the increased furans (2.3-20.9%) from U fruit to RG fruit that characterized a sweet and fruity aroma. Consumers didn't detect differences in sensory attributes of the analyzed R and RG fruits. The data showed that the chemical and volatile composition of the fruit was influenced by the ripening stage of the pulp. This is the first time that a study about ripening in sapota-do-Solimões has been reported.

Comparison of the Stability of Mandibular Sagittal Osteotomy Fixation between Two Types of Titanium Miniplates: A Biomechanical Study in Sheep Mandibles.

This study aimed to compare the biomechanical stability of the fixation of mandibular sagittal split osteotomy of the ramus by two types of titanium miniplates in sheep mandibles. Seven preserved sheep mandibles with similar weight and size were selected, dissected with complete removal of soft-tissue structures, and sectioned in their midline. After performing sagittal split osteotomy, 5 mm of advancement was standardized and samples were divided into two groups according to the type of titanium miniplate (GI = seven hemimandibles were fixed with straight titanium miniplate, GII = seven hemimandibles were fixed with L-shaped titanium miniplates), and then subjected to compressive load. The means (standard deviation) of the compressive load and extension values were 70.68 N (22.26) and 63.36 mm (15.60) to straight miniplates, and 78.80 N (32.54) and 70.55 mm (5.42) to L-shaped miniplates. After comparison and statistical analysis, the results showed no significant difference between the two types of titanium miniplates.