Resolve and dissolve-An ultrasound-guided investigation on the effects of hyaluronidase on different soft tissue fillers.

BACKGROUND: Nonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)-based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA-based products differing in product characteristics, thereby catering to an ever-widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase. OBJECTIVE: To analyze the response of different HA-based soft tissue filler materials to hyaluronidase injections. METHODS: A total of 11 different HA-based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA-based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection. RESULTS: Regardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow-up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow-up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1-structuring, Group 2-volumizing). CONCLUSION: The effectiveness of hyaluronidase in dissolving HA-based fillers is initially independent of product characteristics of HA-based fillers such as G-prime, with increased efficacy in fillers with higher G-prime values, as evidenced by significant volume reductions in such groups.

First description of a primary esophageal histiocytic sarcoma in a dog.

An 11-year-old male Schnauzer dog was referred for investigation of cough and regurgitation of one month duration and gradual hyporexia for the previous five months. Complete blood count showed severe leukocytosis. On ventrodorsal and lateral thoracic radiographs a soft tissue mass was visible in the craniodorsal mediastinum. Endoscopy showed esophageal dilatation and an irregular, nodular, friable, exophytic mass in the thoracic esophagus, which was invasive, vascularized and had ulcerated areas. The mass occluded approximately 90% of the esophageal lumen. The mucosa in the orad portion of the thoracic esophagus was pale and the aborad portion was hyperemic (red) with hemorrhages. The mucosa of the cervical and abdominal esophagus was macroscopically unremarkeble. Multiple biopsies using endoscopic cup biopsy forceps were taken from the mass for histopathologic analysis and a percutaneous endoscopic gastrostomy was performed. Histopathologic analysis of the biopsy samples was inconclusive due to the marked necrosis. The poor clinical condition of the dog precluded a more invasive approach, and palliative and supportive treatment was continued. After 100 days of follow-up, clinical signs worsened, and that day the dog had a fatal cardiac arrest due to aspiration pneumonia and sepsis. Postmortem examination showed a multilobulated mass in the esophageal wall with infiltration into the overlying esophageal mucosa and pulmonary and renal metastases. Histological examination revealed a poorly differentiated sarcoma. On immunohistochemical examination, the neoplastic cells showed marked cytoplasmic staining for vimentin and Iba-1. The proliferative rate was approximately 30% by Ki-67. Histological and immunohistochemical examination revealed the esophageal mass to be a primary histiocytic sarcoma. Histiocytic sarcoma is an extremely rare primary esophageal neoplasm in humans, and so far, there is no description in dogs. To the best of the authors knowledge this is the first case of primary esophageal histiocytic sarcoma in dogs. The clinical information reported here should improve recognition and aid in diagnosis of future cases.

Analysis of the use of isotretinoin as an adjuvant in rhinoplasty.

BACKGROUND: Isotretinoin has been used in the treatment of acne for decades through the reduction of sebaceous secretion. There are reports in the literature that isotretinoin may be associated with decreased skin thickness, especially in patients with thick nasal skin for whom rhinoplasty can be more challenging. The objective of this study was to quantify, through ultrasonography, the effect of the use of oral isotretinoin in patients undergoing rhinoplasty, pre- and postoperatively. METHODS: Twenty-four patients participated in this randomized, single-blind controlled pilot clinical trial. The intervention group used oral isotretinoin (20 mg/day) for 2 months before rhinoplasty and for 4 months after. Both groups underwent rhinoplasty in the same plastic surgery department and were submitted to high-frequency (22 MHz) ultrasound evaluation of the epidermis and dermis on the nasal dorsum, nasal tip, and left nose wing at the beginning of the study and 6 months after rhinoplasty, with the aim of assessing changes in skin thickness. RESULTS: Six months after rhinoplasty, a statistically significant reduction was observed in the thickness of the epidermis and dermis of the nasal dorsum and left nose wing, as well as of the epidermis of the nasal tip, but only in the intervention group. The results of the satisfaction questionnaire were better after rhinoplasty in both groups, with no statistical difference between them regarding the specific questions; however, the intervention group had significantly higher satisfaction scores than the control group. CONCLUSIONS: Isotretinoin was effective in reducing the thickness of the skin covering the nose of the evaluated sites.

Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design.

With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine potency and/or modulate immune response quality while reducing off-target effects. With mRNA-vaccines establishing themselves as a versatile technology for future applications, in the last years several approaches have been explored to target nanoparticles-enabled mRNA-delivery systems to immune cells, with a focus on dendritic cells. Dendritic cells (DCs) are the most potent antigen presenting cells and key mediators of B- and T-cell immunity, and therefore considered as an ideal target for cell-specific antigen delivery. Indeed, improved potency of DC-targeted vaccines has been proved in vitro and in vivo. This review discusses the potential specific targets for immune system-directed mRNA delivery, as well as the different targeting ligand classes and delivery systems used for this purpose.

Lesões periapicais de origem não-endodôntica: uma revisão integrativa

O objetivo deste trabalho foi elencar quais são as principais lesões periapicais que não têm origem a partir da necrose pulpar. Para tanto, realizou-se uma revisão integrativa da literatura, com busca nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Medical Literature Analysis and Retrievel System Online (MEDLINE) e Bibliografia Brasileira de Odontologia (BBO). Os descritores utilizados foram "doenças periapicais" e "diagnóstico diferencial", combinados com o operador booleano "AND". Foram encontrados 42 artigos que responderam aos critérios de inclusão e exclusão. A análise dos estudos incluídos mostrou que as principais lesões periapicais de origem não endodôntica são o queratocisto odontogênico e o ameloblastoma. Embora a prevalência de lesões periapicais não endodônticas seja baixa, é importante estar atento aos possíveis diagnósticos diferenciais, visto que as lesões que mais apareceram na literatura se tratam de patologias localmente agressivas e potencialmente mutiladoras. Ademais, a conduta do profissional que se depara com qualquer tipo de lesão periapical que apresente comportamento fora dos padrões de normalidade deve ser a realização de biópsia e análise histopatológica.

The aim of this study was to list the main periapical lesions that do not originate from pulpal necrosis. An integrative literature review was carried out, with a search in the Latin American and Caribbean Literature in Health Sciences (LILACS), Medical Literature Analysis and Retrievel System Online (MEDLINE) and Bibliografia Brasileira de Odontologia (BBO) databases. The keywords used were "periapical diseases" and "differential diagnosis", combined with the boolean operator "AND". 42 articles were found that met the inclusion and exclusion criteria. The analysis of the included studies showed that the main periapical lesions of non-endodontic origin are the odontogenic keratocyst and the ameloblastoma. Although the prevalence of non-endodontic periapical lesions is low, it is important to be aware of possible differential diagnoses, since the lesions that most appeared in the literature are locally aggressive and potentially mutilating pathologies. In addition, the conduct of the professional who is faced with any type of periapical lesion that presents behavior outside the normal range should be to perform a biopsy and histopathological analysis.

Birefringence analysis of collagen supraorganization in cat corneas with tropical keratopathy.

OBJECTIVE: To evaluate the birefringent properties of the cornea and examine the supraorganizational aspects of collagen fibers in cats with tropical keratopathy. PROCEDURE: In this study, 10-micrometer-thick sections of corneal tissue from cats with tropical keratopathy were examined, both in the opaque and transparent areas of the anterior stroma. Control samples were obtained from healthy cat corneas. Polarized light microscopy was employed to evaluate the birefringent properties using two distinct methods. The first method involved measuring the optical retardation associated with corneal birefringence, while the second method assessed the alignment/waviness of the birefringent collagen fibers. Differences were significant when p < .05. RESULTS: Tropical keratopathy resulted in a significant rise (p < .05) in optical retardation in both opaque and transparent regions of the cat cornea. In the anterior stroma, both the opaque zones and transparent tissue exhibited a higher degree of collagen fiber packing than the control corneas. However, no significant differences (p > .05) in alignment were observed between the transparent tissue of the diseased cornea and the healthy corneas. CONCLUSION: Supraorganizational changes in collagen fiber packing are not restricted to lesion zones in cat corneas affected by tropical keratopathy. Such alterations also occur in the corneal tissue of the anterior stroma adjoining the lesions. Therefore, it is plausible that the transparent tissue of the anterior stroma in corneas affected by the disease may have functional abnormalities, despite its macroscopic healthy appearance. Additional investigations are required to clarify the implications of these potential defects and their conceivable contribution to tropical keratopathy.

Comedonic lupus, a rare variant of chronic cutaneous lupus erythematosus (CCLE): case series and literature review.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is an autoimmune disease with several clinical presentations. The chronic form predominantly presents as discoid rashes but may present with less common morphological findings that can sometimes make diagnosis difficult. Comedonic lupus is a rare and underdiagnosed variant, with unknown etiology and still poorly defined treatment. METHODS: The report illustrates a series of five cases of patients diagnosed with comedonic lupus, and it reviews 18 cases previously published in the literature. RESULTS: The clinical presentation is of comedonal lesions, mostly located on the face, making a differential diagnosis with other benign conditions such as acne vulgaris, Favre-Racouchot syndrome, and syringoma, emphasizing the importance of clinical practice and histopathology for diagnostic confirmation. CONCLUSIONS: There is scarcity in the literature regarding the condition and therapeutic possibilities for these cases of comedonic lupus.

Evaluation of a novel restorative protocol to treat non-carious cervical lesion associated with gingival recession: a 2-year follow-up randomized clinical trial.

OBJECTIVE: To compare 2 different resin composites and 2 adhesive systems used in a new restorative protocol (partial restoration) to treat non-carious cervical lesions associated with gingival recession type 1 (RT1). MATERIAL AND METHODS: Eighty combined defects (CDs) were treated with a partial restoration and periodontal plastic surgery for root coverage. The CDs were randomly assigned to one of the following groups: NP + TE (n = 20), nanofilled composite and 2-step total-etch adhesive system; NP + UA (n = 20), nanofilled composite and universal adhesive system; MH + TE (n = 20), microhybrid composite and 2-step total-etch adhesive; MH + UA (n = 20), microhybrid composite and universal adhesive. Restorations were assessed using the United States Public Health Service (USPHS) criteria at 1 week (baseline) and 6, 12, and 24 months. Survival rate, periodontal parameters, dentin hypersensitivity (DH), and aesthetics were also evaluated. RESULTS: After 24 months, only the MH + TE group did not lose any restoration, with no significant differences between groups. For surface roughness parameter, MH presented 83.3% of the restorations scoring Bravo, whereas NP presented 48.5% of the restorations scoring Bravo. All groups presented restorations with marginal discoloration. All periodontal parameters behaved similarly, regardless of the restorative material. All groups presented significant reductions of dentin hypersensitivity and improved aesthetic perceptions (p < 0.05). CONCLUSION: Both resin composites and adhesives tested can be combined for partial restorations to treat CDs. CLINICAL RELEVANCE: This new restorative-surgical protocol to treat CDs presents satisfactory outcomes. The partial restorations can be successfully executed with both combinations of adhesives and resin composites evaluated in this investigation. TRN : ClinicalTrial.gov: NCT03215615; registration date July 12, 2017.

The Effect of Clomiphene Citrate and Letrozole in Apoptotic Pathways and Cell Cycle in Human Primary Cumulus Cells and the Protective Effect of Estradiol.

Clomiphene citrate (CC) and letrozole are ovulatory stimulants that, despite high ovulation rates, achieve low pregnancy rates. This study aimed to investigate the in vitro effects of CC and letrozole, alone or in combination with estradiol, on apoptosis in human cumulus cells. We performed a controlled prospective study using primary cumulus cell cultures from patients undergoing in vitro fertilization (n=22). Alpha-inhibin immunocytochemistry was used to assess cell culture purity and morphology. Cell viability was evaluated by MTT assay, cell cycle status by flow cytometry, and Caspase-3, Bax and SOD-2, and S26 gene expression by qPCR. Cells were treated for 24 hours in 5 conditioned media: CC, CC + estradiol, letrozole, letrozole + estradiol and control. None of the treatments affected cell viability, but letrozole reduced the mean percentage of cells in the S phase compared to control (24.79 versus 21.70, p=0.0014). Clomiphene treatment increased mRNA expression of Bax (4 fold) and SOD-2 (2 fold), which was reversed by co-treatment with estradiol. SOD-2 expression increased in cells treated with letrozole compared to control (4 fold), which was also reversed by estradiol. These findings suggest that clomiphene citrate and letrozole do not significantly affect the viability of human cumulus cells. Still, the expression of genes involved in apoptosis was modulated by these drugs alone and in association with estradiol, suggesting that CC and letrozole may have direct effects on cumulus cells beyond their known mechanisms of action.

A Nanoscale Shape-Discovery Framework Supporting Systematic Investigations of Shape-Dependent Biological Effects and Immunomodulation.

Since it is now possible to make, in a controlled fashion, an almost unlimited variety of nanostructure shapes, it is of increasing interest to understand the forms of biological control that nanoscale shape allows. However, a priori rational investigation of such a vast universe of shapes appears to present intractable fundamental and practical challenges. This has limited the useful systematic investigation of their biological interactions and the development of innovative nanoscale shape-dependent therapies. Here, we introduce a concept of biologically relevant inductive nanoscale shape discovery and evaluation that is ideally suited to, and will ultimately become, a vehicle for machine learning discovery. Combining the reproducibility and tunability of microfluidic flow nanochemistry syntheses, quantitative computational shape analysis, and iterative feedback from biological responses in vitro and in vivo, we show that these challenges can be mastered, allowing shape biology to be explored within accepted scientific and biomedical research paradigms. Early applications identify significant forms of shape-induced biological and adjuvant-like immunological control.

Single gingival recession associated with non-carious cervical lesion treated by partial restoration and coronally advanced flap with or without xenogenous collagen matrix: A randomized clinical trial evaluating the coverage procedures and restorative protocol.

BACKGROUND: Evaluate the use of collagen matrix (CM) as adjunctive to coronally advanced flap (CAF versus CAF + CM) to treat gingival recession (GR) associated with non-carious cervical lesion-combined defects (CDs). METHODS: Sixty-two patients presenting 62 CDs (RT1 GR and non-carious cervical lesion (NCCLs) were randomly allocated to either CAF group (n = 31): partial restoration of the NCCL and CAF; or to CAF + CM group (n = 31): partial restoration of the NCCL and CAF associated with CM. Clinical, esthetic, patient-centered outcomes, and restorative parameters were assessed. RESULTS: After 12 months, CD coverage were 55.2% for CAF and 54.4% for CAF + CM (P = 0.8). Recession reduction were 1.9 ± 0.8 mm for CAF and 2.0 ± 0.7 mm for CAF + CM (P = 0.6). CAF+CM resulted in higher increase in keratinized tissue (KT) width (CAF: 0.3 ± 0.7 mm; CAF + CM: 0.9 ± 0.8 mm; P = 0.004) and KT thickness gain (CAF: 0.1 ± 0.3 mm; CAF + CM: 0.7 ± 0.2 mm; P = 0.001). Both treatments presented low postoperative pain and resulted in esthetics improvements. In addition, no restoration was lost, 27.4% showed a reduction of the superficial polishing, and 8% showed marginal staining, but still clinically acceptable. CONCLUSION: Partial resin composite restoration (with the apical limit up to 1 mm of the estimated CEJ) and CAF alone or combined with CM are suitable for treating CDs. The use of CM provided additional benefits in terms of KT width and thickness gain. (NCT03341598).

Nanoscale shape-dependent histone modifications.

Recent observations suggest a role for complex nanoscale particulate shape in the regulation of specific immune-related cellular and in vivo processes. We suspect that cellular recognition of nanostructure architecture could involve nonmolecular inputs, including cellular transduction of nanoscale spatially resolved stresses induced by complex shape. Here, we report nanoscale shape-dependent control of the cellular epigenome. Interpretation of ChIP-Seq sequencing suggests that differential marking of H3K27me3 may be linked to sensory and synapse-recognition of nanoscale forces induced by complex shape. The observations raise significant questions on the role of particle-shape-induced immune regulation and memory, with potential consequences in both causes and treatment of immune-related disease.

A nano perspective behind the COVID-19 pandemic.

The global pandemic scenario has definitely pushed the scientific community to develop COVID-19 vaccines at unprecedented speed. Nevertheless, a worldwide vaccination campaign is still far from being achieved, making the usual precautionary measures as necessary as at the beginning of the outbreak. Many aspects of the SARS-CoV-2 infectious potential and disease severity do not solely rely on interactions at the molecular level but also on physical-chemical parameters that often involve nanoscale effects. Here the SARS-CoV-2 journey to infect a susceptible host is reviewed, focusing on the nanoscale aspects that play a role in the viral infectivity and disease progression. These nanoscale-driven interactions are essential to establish mitigation-related strategies.