Photobiomodulation enhances the Th1 immune response of human monocytes.

This study aims to evaluate the effects of photobiomodulation (PBM) on human monocytes, assessing the oxidative burst and ultimate fungicidal potential of these cells, as well as the gene expression at the mRNA level of CD68, CD80, CD163, CD204, IL-6, TNF-α and IL-10 in derived macrophages. Primary cultures of human monocytes were irradiated with an InGaAlP (660 nm)/GaAlAs (780 nm) diode laser (parameters: 40 mW, 0.04 cm2, 1 W/cm2; doses: 200, 400 and 600 J/cm2). Cells were submitted to the chemiluminescence assay, and a microbicidal activity assay against Candida albicans was performed. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured, and cell viability was assessed by the exclusion method using 0.2% Trypan blue reagent. Irradiated monocytes were cultured for 72 h towards differentiation into macrophages. Total RNA was extracted, submitted to reverse transcription and real-time PCR. The results were analysed by ANOVA and the Tukey test (α = 0.05). Irradiated monocytes revealed a significant increase in their intracellular and extracellular ROS (P < 0.001). The 660 nm wavelength and 400 J/cm2 dose were the most relevant parameters (P < 0.001). The fungicidal capacity of the monocytes was shown to be greatly increased after PBM (P < 0.001). PBM increased the expression of TNF-α (P = 0.0302) and the production of NO (P < 0.05) and did not impair monocyte viability. PBM induces a pro-inflammatory Th1-driven response in monocytes and macrophages.

ß-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity.

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in ß-cyclodextrin (ß-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:ß-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:ß-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:ß-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:ß-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

Conservative surgical treatments for nonsyndromic odontogenic keratocysts: a systematic review and meta-analysis.

OBJECTIVES: This manuscript presents a systematic review of the clinicopathologic features and outcomes of conservative surgical treatments for nonsyndromic odontogenic keratocysts (OKCs) and assesses the recurrence rates through a meta-analysis, in order to indicate the best conservative approach. MATERIALS AND METHODS: PRISMA guidelines for systematic reviews were followed, and the protocol was registered (PROSPERO/Nr.: CRD42017060964). An electronic search was conducted using the PubMed/MEDLINE, Science Direct, Web of Science, Scopus, and The Cochrane Library databases, and relevant articles were selected based on specific inclusion criteria. The PICOS criteria (Population: nonsyndromic patients of any age with OKC, with histopathological diagnosis and minimum follow-up of 12 months; Intervention and Comparison: marsupialization or decompression with or without enucleation, and enucleation alone; Outcome: recurrence rates; Study design: clinical trials, controlled trials, retrospective studies, and case series containing at least 10 cases of OKC) were employed. A pooled odds ratio (OR) was computed through the Mantel-Haenszel test (M-H) with 95% confidence intervals (CI). RESULTS: One thousand nine hundred OKCs were analyzed; the age of the patients varied from 6 to 90 years (mean of 38.6 years); a male to female ratio of 1.57:1 was observed; 74.5% of the lesions occurred in the mandible; 75.7% of OKCs were unilocular; the association with impacted tooth was reported for 344 OKCs; and the mean follow-up was 60.1 months. One thousand three hundred thirty-one OKCs were treated by conservative surgical treatments, and 261 cases (19.8%) presented recurrence. Nonetheless, minor total recurrence rates were observed after decompression followed by enucleation (11.9%) and marsupialization followed by enucleation (17.8%). In contrast, enucleation alone showed a total recurrence rate of 20.8%. CONCLUSION: The results suggest a significant superiority of success for OKC treatments that use decompression followed by enucleation, instead of an initial enucleation (M-H, OR = 0.48; 95% CI = 0.22 to 1.08; P = 0.0163). CLINICAL RELEVANCE: No consensus exists concerning the best management for OKCs. More aggressive treatments (ostectomy, resection, or use of adjunctive therapies like Carnoy's solution and liquid nitrogen) can have many disadvantages and risks. Therefore, it is necessary to identify the conservative approach for OKCs that results in a lower recurrence rate.

Fatal primary diffuse large B-cell lymphoma of the maxillary sinus initially treated as an infectious disease in an elderly patient: A clinicopathologic report.

OBJECTIVE: To report a case of primary diffuse large B-cell lymphoma (DLBCL) of the maxillary sinus in an 82-year-old Caucasian woman. BACKGROUND: Diffuse large B-cell lymphoma of the maxillary sinus has non-specific signs and symptoms that may be confused with benign inflammatory conditions and upper respiratory infections. METHODS: An incisional biopsy was performed. CD20+ /CD3- /Ki-67: 95% cells were observed. CONCLUSION: A good medical history, clinical and imaging evaluations and immunohistochemical reactions are crucial to establish a correct and early diagnosis of DLBCL.

Impact of the COVID-19 pandemic on head and neck cancer patients: systematic review and meta-analysis.

OBJECTIVES: This manuscript presents a systematic review of the impact of the COVID-19 pandemic on head and neck cancer (HNC) patients. A meta-analysis was made to compare the number of treated/operated HNC patients in the pre-COVID-19 era versus the COVID-19 era. This investigation was based on previous reports showing a delay in the diagnosis and treatment of new cases of cancer during the pandemic. Worsening in cancer prognosis would be expected as a result of the delayed treatments. METHOD AND MATERIALS: An electronic search was conducted using the PubMed/MEDLINE, Embase, Web of Science, Scopus, and The Cochrane Library databases. Relevant articles were selected based on specific inclusion criteria. RESULTS: A total of 8,942 HNC patients were included. A higher prevalence in male (1,873) in comparison to female (1,695) was observed considering 3,568 patients. Regarding staging, the majority of cases were stage III to IV. The treatment type more frequently described was surgery. Positive diagnosis for COVID-19 in the pre-oncologic treatment was reported for 242 patients, and for post-oncologic treatment in 119 patients. Mortality by COVID-19 was reported for 27 HNC patients. The meta-analysis revealed a significantly smaller number of surgeries/oncologic treatments of HNC patients performed (2,666) in the COVID-19 era when compared to the pre-COVID-19 era (3,163) (Mantel-Haenszel odds ratio = 0.81, 95% CI = 0.65 to 1.00, P = .05). CONCLUSION: The impact of the COVID-19 pandemic on HNC patients occurred mainly in the number of surgeries/oncologic treatments, showing a significantly smaller number of surgeries/oncologic treatments performed in the COVID-19 era rather than the pre-COVID-19 era.

Exposure to copper sulfate impairs survival, post-embryonic midgut development and reproduction in Aedes aegypti.

Aedes aegypti is a vector of several global human viruses responsible for high human morbidity and mortality. The method to prevent the transmission of vector-borne viruses is mainly based on the control of the insect vector using insecticides. Among these chemicals, copper sulfate is a compound widely used in agriculture with the potential to be used as an alternative to control these insects. This study evaluated the effects of the exposure of A. aegypti larvae to copper sulfate on survival, midgut morphology, blood-feeding and fecundity. The exposure to CuSO4 decreased the survival of A. aegypti during the immature phase. Adults obtained from exposed larvae had their lifespan decreased at all tested concentrations. The exposure to CuSO4 impaired the development in the transition from larvae to pupae and from pupae to adult. The number of eggs laid by females developed from larvae treated with CuSO4 was significantly lower than in control. In addition, the egg hatching rates were also negatively affected. The midguts of treated larvae and pupae showed epithelial disorganization. The number of cleaved caspase-3 cells increased in the midgut of exposed pupae compared to control. Moreover, there was a reduction in proliferating cells in treated larvae and pupae compared to the control. In conclusion, the results reveal that CuSO4 exposure has insecticidal activity against A. aegypti, which may be related to the impairment of the midgut metamorphosis and reduced proliferation of stem cells, with the consequent impairment of female mosquito fertility and fecundity.

Carriers based on poly-3-hydroxyalkanoates containing nanomagnetite to trigger hormone release.

Poly-3-hydroxybutyrate (P(3HB)) and poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (P(3HB-co-3HHx)) are biocompatible and bioabsorbable biopolymers produced by different bacteria with potential for drug delivery in thermo-responsive magnetic microcarriers. Microparticles of P(3HB) and P(3HB-co-3HHx), with 5.85% mol of 3HHx, produced by Burkholderia sacchari, containing nanomagnetite (nM) and lipophilic hormone were prepared by simple emulsion (oil/water) technique leading to progesterone (Pg) encapsulation efficiency higher than 70% and magnetite loads of 3.1 and 2.3% (w/w) for P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg, respectively. These formulations were characterized by Infrared spectroscopy, X-ray diffraction, Thermal gravimetric analysis and Electron microscopy (TEM, SEM) techniques. The P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg microparticles presented spherical geometry with wrinkled surfaces and average size between 2 and 40 µm for 90% of the microparticles. The release profiles of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg formulations showed a hormone release trigger (6.9 and 11.1%, respectively) effect induced by oscillating external magnetic field (0.2 T), after 72 h. Progesterone release in non-magnetic tests with P(3HB-co-3HHx)/nM/Pg revealed a slight increment (5.6%) in relation to P(3HB)/nM/Pg. The experimental release of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg samples presented a good agreement with Higuchi model. The 3HHx comonomer content improves the hormone release of the P(3HB-co-3HHx)/nM/Pg formulation with potential for application to synchronize the estrous cycle.

Spiromesifen induces histopathological and cytotoxic changes in the midgut of the honeybee Apis mellifera (Hymenoptera: Apidae).

The honeybee Apis mellifera is an important pollinator that, similarly to other bees, undergoes colony losses due to several problems, including the use of pesticides in the agriculture. In addition to direct mortality, pesticides cause side-effects in some non-target organs, such as the midgut, which is the main organ for digestion and absorption. Spiromesifen is a pesticide used to control mites and whiteflies, which can be ingested by bees feeding on contaminated floral resources. This study evaluated the histopathological and cytological effects of the ingestion of spiromesifen on the midgut of A. mellifera workers. The bees were exposed per os to the field recommended dose of spiromesifen, and the midgut was analyzed after 24h and 48h of exposure to the pesticide. The midgut has a single layer of digestive cells, with spherical nucleus, nests of regenerative cells and layers of peritrophic matrix in the lumen. Bees treated with spiromesifen presented histological and cytological changes in the midgut, including disorganization of the epithelial architecture, release of cell fragments to the lumen, accumulation of mitochondria in the apical cytoplasm, alteration of the basal labyrinth, changes in the rough endoplasmic reticulum and cell degeneration. The occurrence of damage in the digestive cells of the A. mellifera midgut indicates that spiromesifen does not cause mortality in honeybees, but its side-effects can damage the midgut, which may affect the longevity and behavior of this pollinator.

Cytotoxic effects on the midgut, hypopharyngeal, glands and brain of Apis mellifera honey bee workers exposed to chronic concentrations of lambda-cyhalothrin.

The honeybee, Apis mellifera is economically important for its products (honey, wax, and propolis) and for its role in pollination. This insect is threated due to high population losses in both agriculture and beekeeping. Within causes involved in the loss of honeybees is the increased pesticide use on agriculture. Although current testing for the regularization of insecticide use considers its acute toxic effects on pollinators, little is known about the effects of chronic exposure to sublethal concentrations that may persist in the environment. This study investigated the effect of chronic exposure to sublethal concentrations of lambda-cyhalothrin on the midgut, hypopharyngeal glands, and brain of A. mellifera. Honey bees were fed for eight days with LC50/100 insecticide. Subsequently, the midgut, hypopharyngeal glands, and brain were analyzed in light and transmission electron microscopies. The midgut was not affected after exposure, except in the posterior region with cell fragments in the lumen and changes in the mitochondria. The hypopharyngeal glands were severely affected by the insecticide with changes in the rough endoplasmic reticulum and cell death. The brain has extensive gaps in the neuropil as well as in the cellular bodies, especially in the corpora pedunculata. These resembled cellular alterations similar to those seen in death processes. The results of this study indicate that lambda-cyhalothrin is toxic to bees at sublethal concentrations and ingested chronically, causing damage to the midgut, hypopharyngeal glands, and brain, and may affect physiological and behavioral aspects of these insects.

Primary oral melanoma: A clinicopathologic review and case presentation.

OBJECTIVE: The purpose of this manuscript is to present a clinicopathologic review of the literature concerning all the detailed cases of primary oral melanoma (OM) that were confirmed by immunohistochemistry. In addition, a pertinent case presentation is addressed. DATA SOURCES: An extensive electronic search of the literature was performed using PubMed/Medline from 1953 to 2017. Relevant articles were selected based on specific inclusion criteria. Statistical analyses were conducted by the Shapiro-Wilk, Fisher's exact, chi-square, and Z tests (α = .05). RESULTS: Forty-nine cases of primary OM reported in the literature plus the current case were analyzed; patient ages ranged from 17 to 89 years with a mean of 60.8 years; male to female ratio was 1.5:1; Caucasian patients were the most affected and the most frequent locations were maxillary alveolar mucosa and palate; the majority of the lesions were pigmented (62%); differences among the proportions of positivity to S-100, HMB-45, Melan-A, NKFC3, vimentin, tyrosinase, CK, microphthalmia transcription factor (MITF), and Ki-67 were found (P < .0001), especially when comparing with vimentin (P < .05) and CK (P < .01); recurrence was reported in 11.6% and mortality in 54.8%. The case presented is of a 71-year-old mixed-race woman who presented multiple pigmented lesions over the maxillary alveolar mucosa and palate. Positivity for S-100, HMB-45, Melan-A, and Ki-67 confirmed the diagnosis of primary OM. CONCLUSION: Primary OM is rare and very aggressive, with only 49 detailed cases confirmed by immunohistochemistry existing within the English literature, in addition to the present case. S-100 and HMB-45 are excellent markers to confirm the diagnosis of primary OM, although the use of adjuvant specific markers such as Melan-A, tyrosinase, and MITF should be also encouraged.

Photodynamic therapy for Schistosoma mansoni: Promising outcomes.

The purpose of this study was to assess, for the very first time, the effects of photodynamic therapy (PDT) on Schistosoma mansoni in vitro by measuring reactive oxygen species (ROS) generation throughout the treatment, as well as the behavior of the parasites (mating, motility and contraction/shortening), and damage to their tegument and excretory systems. The parasites were divided into 4 groups: control, photosensitizer, laser and PDT. Light irradiation was delivered with an InGaAlP low-level laser device operating at 660nm, with 40mW and 100J/cm2. For PDT, different toluidine blue dye (TBO) concentrations and times of exposure were utilized. Interestingly, TBO-mediated PDT was able to kill S. mansoni (P<0.001) due to the significant amount of ROS released that inflicted damages in the tegument and excretory system, as well as contraction and cessation of motility. In addition, males of S. mansoni were shown to be more sensitive to PDT if compared to their corresponding females when the optimal TBO concentration of 31.2µL was considered (P=0.0126). PDT presents two major advantages: not inducing microbial resistance and also lacking adverse effects. Therefore, PDT may become a promising therapeutic alternative for schistosomiasis in the near future, especially for cases of allergy and resistance to praziquantel.